CD001800 PDF

Exercise-based cardiac rehabilitation for coronary heart disease (Review)
Heran BS, Chen JMH, Ebrahim S, Moxham T, Oldridge N, Rees K, Thompson DR, Taylor RS
This is a reprint of a Cochrane review, prepared and maintained by The Cochrane Collaboration and published in The Cochrane Library 2011, Issue 8 http://www.thecochranelibrary.com
Exercise-based cardiac rehabilitation for coronary heart disease (Review) Copyright 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
TABLE OF CONTENTS HEADER . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ABSTRACT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . PLAIN LANGUAGE SUMMARY . . . . . . . . . . . . . . . . . . . . . . . . . . . . BACKGROUND . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . OBJECTIVES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . METHODS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . RESULTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Figure 1. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Figure 2. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . DISCUSSION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . AUTHORS CONCLUSIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ACKNOWLEDGEMENTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . CHARACTERISTICS OF STUDIES . . . . . . . . . . . . . . . . . . . . . . . . . . . DATA AND ANALYSES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 1.1. Comparison 1 Exercise-based rehabilitation versus usual care, Outcome 1 Total mortality. . . . Analysis 1.2. Comparison 1 Exercise-based rehabilitation versus usual care, Outcome 2 Cardiovascular mortality. Analysis 1.3. Comparison 1 Exercise-based rehabilitation versus usual care, Outcome 3 Fatal and/or nonfatal MI. Analysis 1.4. Comparison 1 Exercise-based rehabilitation versus usual care, Outcome 4 CABG. . . . . . . Analysis 1.5. Comparison 1 Exercise-based rehabilitation versus usual care, Outcome 5 PTCA. . . . . . . Analysis 1.6. Comparison 1 Exercise-based rehabilitation versus usual care, Outcome 6 Hospital Admissions. . ADDITIONAL TABLES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . APPENDICES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . WHATS NEW . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . HISTORY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . CONTRIBUTIONS OF AUTHORS . . . . . . . . . . . . . . . . . . . . . . . . . . . DECLARATIONS OF INTEREST . . . . . . . . . . . . . . . . . . . . . . . . . . . . SOURCES OF SUPPORT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . DIFFERENCES BETWEEN PROTOCOL AND REVIEW . . . . . . . . . . . . . . . . . . . NOTES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . INDEX TERMS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 1 2 2 3 3 6 7 10 11 12 12 13 20 69 70 72 73 75 76 77 78 86 90 90 90 91 91 91 91 91
[Intervention Review]
Exercise-based cardiac rehabilitation for coronary heart disease

Balraj S Heran2 , Jenny MH Chen2 , Shah Ebrahim3 , Tiffany Moxham4 , Neil Oldridge5 , Karen Rees6 , David R Thompson7 , Rod S Taylor1 College of Medicine and Dentistry, Universities of Exeter & Plymouth, Exeter, UK. 2 Department of Anesthesiology, Pharmacology and Therapeutics, University of British Columbia, Vancouver, Canada. 3 Department of Non-communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK. 4 Wimberly Library, Florida Atlantic University, Boca Raton, Florida, USA. 5 University of Wisconsin School of Medicine & Public Health and Aurora Cardiovascular Services, Aurora Sinai/Aurora St. Lukes Medical Center, Milwaukee, Wisconsin, USA. 6 Health Sciences Research Institute, Warwick Medical School, University of Warwick, Coventry, UK. 7 Cardiovascular Research Centre, Australian Catholic University, Melbourne, Australia Contact address: Rod S Taylor, Peninsula College of Medicine and Dentistry, Universities of Exeter & Plymouth, Veysey Building, Salmon Pool Lane, Exeter, EX2 4SG, UK. rod.taylor@pms.ac.uk. Editorial group: Cochrane Heart Group. Publication status and date: Edited (no change to conclusions), published in Issue 8, 2011. Review content assessed as up-to-date: 13 June 2010. Citation: Heran BS, Chen JMH, Ebrahim S, Moxham T, Oldridge N, Rees K, Thompson DR, Taylor RS. Exercise-based cardiac rehabilitation for coronary heart disease. Cochrane Database of Systematic Reviews 2011, Issue 7. Art. No.: CD001800. DOI: 10.1002/14651858.CD001800.pub2. Copyright 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
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ABSTRACT Background The burden of coronary heart disease (CHD) worldwide is one of great concern to patients and healthcare agencies alike. Exercisebased cardiac rehabilitation aims to restore patients with heart disease to health. Objectives To determine the effectiveness of exercise-based cardiac rehabilitation (exercise training alone or in combination with psychosocial or educational interventions) on mortality, morbidity and health-related quality of life of patients with CHD. Search methods RCTs have been identied by searching CENTRAL, HTA, and DARE (using The Cochrane Library Issue 4, 2009), as well as MEDLINE (1950 to December 2009), EMBASE (1980 to December 2009), CINAHL (1982 to December 2009), and Science Citation Index Expanded (1900 to December 2009). Selection criteria Men and women of all ages who have had myocardial infarction (MI), coronary artery bypass graft (CABG) or percutaneous transluminal coronary angioplasty (PTCA), or who have angina pectoris or coronary artery disease dened by angiography. Data collection and analysis Studies were selected and data extracted independently by two reviewers. Authors were contacted where possible to obtain missing information.
Exercise-based cardiac rehabilitation for coronary heart disease (Review) Copyright 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. 1
Main results This systematic review has allowed analysis of 47 studies randomising 10,794 patients to exercise-based cardiac rehabilitation or usual care. In medium to longer term (i.e. 12 or more months follow-up) exercise-based cardiac rehabilitation reduced overall and cardiovascular mortality [RR 0.87 (95% CI 0.75, 0.99) and 0.74 (95% CI 0.63, 0.87), respectively], and hospital admissions [RR 0.69 (95% CI 0.51, 0.93)] in the shorter term (< 12 months follow-up) with no evidence of heterogeneity of effect across trials. Cardiac rehabilitation did not reduce the risk of total MI, CABG or PTCA. Given both the heterogeneity in outcome measures and methods of reporting ndings, a meta-analysis was not undertaken for health-related quality of life. In seven out of 10 trials reporting healthrelated quality of life using validated measures was there evidence of a signicantly higher level of quality of life with exercise-based cardiac rehabilitation than usual care. Authors conclusions Exercise-based cardiac rehabilitation is effective in reducing total and cardiovascular mortality (in medium to longer term studies) and hospital admissions (in shorter term studies) but not total MI or revascularisation (CABG or PTCA). Despite inclusion of more recent trials, the population studied in this review is still predominantly male, middle aged and low risk. Therefore, well-designed, and adequately reported RCTs in groups of CHD patients more representative of usual clinical practice are still needed. These trials should include validated health-related quality of life outcome measures, need to explicitly report clinical events including hospital admission, and assess costs and cost-effectiveness.
PLAIN LANGUAGE SUMMARY Regular exercise or exercise with education and psychological support can reduce the likelihood of dying from heart disease. Coronary heart disease (CHD) is one of the most common forms of heart disease. It affects the heart by restricting or blocking the ow of blood around it. This can lead to a feeling of tightness in the chest (angina) or a heart attack. Exercise-based cardiac rehabilitation aims to restore people with CHD to health through either regular exercise alone or a combination of exercise with education and psychological support. The ndings of this review indicate that exercise-based rehabilitation reduces the likelihood of dying from heart disease and there is moderate evidence of an improvement in quality of life in the predominantly middle aged, male patients included in these studies. More research is needed to assess the overall health impact of exercise-based rehabilitation in a broader range of patients.
BACKGROUND
Description of the intervention

Cardiac rehabilitation has been dened as the coordinated sum of interventions required to ensure the best physical, psychological and social conditions so that patients with chronic or post-acute cardiovascular disease may, by their own efforts, preserve or resume optimal functioning in society and, through improved health behaviours, slow or reverse progression of disease (Fletcher 2001). It is a complex intervention that may involve a variety of therapies, including exercise, risk factor education, behaviour change, psychological support, and strategies that are aimed at targeting traditional risk factors for cardiovascular disease. Cardiac rehabilitation is an essential part of contemporary heart disease care and is considered a priority in countries with a high prevalence of CHD. International clinical guidelines consistently identify exercise therapy as a central element of cardiac rehabilitation (Balady 2007;
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Description of the condition

Cardiovascular disease accounts for one-third of deaths globally, with 7.22 million deaths from coronary heart disease (CHD) in 2002 (WHO 2004). In Europe, CHD is the most common cause of death and in the UK it accounts for one in ve deaths in men and one in six deaths in women (British Heart Foundation 2005; Peterssen 2005). Although the mortality rate from CHD has been falling in the UK, principally due to a reduction in risk factors, particularly smoking, it has fallen less than in many other developed countries (Peterssen 2005). Treatments to individuals, including secondary prevention, explain about 42% of the decline in CHD mortality in the 1980s and 1990s (Unal 2000).
Graham 2007; NICE 2007) i.e. exercise-based cardiac rehabilitation. Despite the recommendations for exercise-based cardiac rehabilitation as an integral component of comprehensive cardiac care of patients with CHD (particularly those following myocardial infarction, revascularization or with angina pectoris) and heart failure, most patients do not receive it (Bethall 2008). Service provision, though predominantly hospital based, varies markedly, and referral, enrolment and completion are suboptimal, especially among women and older people (Beswick 2004). Costs of cardiac rehabilitation services vary by format of delivery.The UK survey suggests that costs can range of 50 to 712 per patient treated depending on the level of stafng, the equipment used and the intensity of the programme (Evans 2002). Previous meta-analyses of the effects of exercise-based cardiac rehabilitation for CHD patients reported a statistically signicant reduction in total and cardiac mortality, ranging from 20% to 32%, in patients receiving exercise therapy compared with usual medical care (Clark 2005; Jolliffe 2001; Oldridge 1988; OConnor 1989). However, the evidence for psychological interventions is less convincing. A Cochrane review showed no evidence of an effect on total mortality, cardiac mortality, or revascularisation although there was a signicant reduction in the number of non-fatal infarctions in the psychological intervention group (OR 0.78 [95% CI 0.67 to 0.90]) compared to usual care (Rees 2004). A Cochrane review of the effect of educational interventions for CHD is currently being undertaken (Brown 2010).
and blood pressure. However, the authors identied a number a limitations in the evidence base: Trials enrolled almost exclusively low-risk, middle-aged men after myocardial infarction. The exclusion or under representation of women, elderly people, and other cardiac groups (post revascularization and angina pectoris) not only limits the applicability of the evidence to contemporary cardiovascular practice but also fails to consider those who may benet most from rehabilitation. The widespread introduction of a variety of drug therapies as part of the routine management of CHD the cardiac patient that were not available at the time of the earliest trials may offset the magnitude of benet associated with exercise-based rehabilitation. It was unclear whether comprehensive (exercise plus psychosocial and/or educational interventions) cardiac rehabilitation offers incremental outcome benets compared to exercise only interventions. There was a lack of robust evidence for the impact on patient health-related quality of life, costs and cost-effectiveness. Additionally, recent meta-analyses of the effects of exercise-based cardiac rehabilitation in patients with CHD have indicated an increase in the number of RCTs since the publication of the original Cochrane review (Clark 2005). The aim of this study is to update the original Cochrane systematic review of the effects of exercise-based rehabilitation for patients with CHD.
How the intervention might work

Exercise training has been shown to have direct benets on the heart and coronary vasculature, including myocardial oxygen demand, endothelial function, autonomic tone, coagulation and clotting factors, inammatory markers, and the development of coronary collateral vessels (Clausen 1976; Hambrecht 2000). However, ndings of the original Cochrane review of exercisebased cardiac rehabilitation for CHD supported the hypothesis that reductions in mortality may also be mediated via the indirect effects of exercise through improvements in the risk factors for atherosclerotic disease (i.e. lipids, smoking and blood pressure) (Taylor 2006).
Changes in this update review In addition to updating the searches, this update review has: (1) formally explored the variation in exercise intervention effects using meta-regression and stratied meta-analysis and (2) not updated exercise capacity and cardiac risk outcomes (i.e. serum lipids, blood pressure, and smoking behaviour).
OBJECTIVES
1. To assess the effectiveness of exercise-based cardiac rehabilitation (exercise training alone or in combination with psychosocial or educational interventions) compared with usual care on mortality, morbidity and health-related quality of life in patients with CHD. 2. To explore the potential study level predictors of exercisebased cardiac rehabilitation in patients with CHD.
Why it is important to do this review

Our original Cochrane review published in 2001 identied a total of 35 RCTs in some 8,440 patients (Jolliffe 2001). This review reported a reduction in total mortality (random effects model, odds ratio: 0.73, 95% condence interval: 0.54 to 0.98) with exercise intervention compared to usual care. Improvements with exercise were also seen in cardiac death, non-fatal MI, lipid prole
METHODS
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Criteria for considering studies for this review
CABG PTCA Restenting Total hospitalisations Cardiovascular hospitalisations Other hospitalisations
Types of studies Randomised controlled trials (RCTs) of exercise-based cardiac rehabilitation versus usual care with a follow-up period of at least six months have been sought.
Secondary outcomes
Types of participants Men and women of all ages, in both hospital-based and community-based settings, who have had a myocardial infarction (MI), or who had undergone revascularisation (coronary artery bypass grafting, percutaneous transluminal coronary angioplasty or coronary artery stent), or who have angina pectoris or coronary artery disease dened by angiography have been included. Studies of participants following heart valve surgery, with heart failure, with heart transplants or implanted with either cardiacresynchronisation therapy (CRT) or implantable debrillators (ICD) have been excluded. Studies of participants who completed a cardiac rehabilitation programme prior to randomisation have also been excluded.
Health-related quality of life assessed using validated instruments (e.g. SF-36, EQ5D) Costs and cost-effectiveness
Search methods for identication of studies

As this review forms part of a broader review strategy, that includes updates of two other Cochrane systematic reviews addressing cardiac rehabilitation (Davies 2010a; Rees 2004) and two new Cochrane reviews - interventions for enhancing uptake and adherence to cardiac rehabilitation (Davies 2010b) and home versus centre-based cardiac rehabilitation (Taylor 2010), a generic broad search was initially undertaken. This generic search was then further updated for the purposes of this specic review. Electronic searches Randomized controlled trials have been identied from the previously published Cochrane review. This list of studies has been updated by the authors searching the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library Issue 4, 2009, MEDLINE (November 2000 to December 2009), EMBASE (November 2000 to December 2009), CINAHL (November 2000 to December 2009), and Science Citation Index Expanded (SCI-Expanded, 1900 to December 2009). Health Technology Assessment (HTA) and Database of Abstracts of Reviews of Effects (DARE) databases have been searched via The Cochrane Library Issue 4, 2009. The generic (cross review) search was undertaken from 2001 (the search end date of the previous Cochrane review of exercise-based cardiac rehabilitation (Jolliffe 2001)) to January 2008 with a further update search up to December 2009 for this specic review. Search strategies were designed with reference to those of the previous systematic review (Jolliffe 2001). MEDLINE, EMBASE and CINAHL were searched using a strategy combining selected MeSH terms and free text terms relating to exercise-based rehabilitation and coronary heart disease with RCT lters. The MEDLINE search strategy was translated into the other databases using the appropriate controlled vocabulary as applicable. Due to time and resource constraints, three databases (AMED, BIDS and SPORTSDISCUSS) included the previous review (Jolliffe 2001) were not searched in this case.
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Types of interventions Exercise-based cardiac rehabilitation is dened as a supervised or unsupervised inpatient, outpatient, or community- or home-based intervention including some form of exercise training that is applied to a cardiac patient population. The intervention could be exercise training alone or exercise training in addition to psychosocial and/or educational interventions (i.e. comprehensive cardiac rehabilitation). Usual care could include standard medical care, such as drug therapy, but did not receive any form of structured exercise training or advice.
Types of outcome measures All clinical events or other outcome measures reported post-randomisation were included in this review. No maximum limit was imposed on the length of follow-up.
Primary outcomes
Total mortality Cardiovascular mortality Non-cardiovascular mortality Total MI Fatal MI Non-fatal MI Total revascularizations
Searches have been limited to randomised controlled trials and a lter applied to limit by humans. Consideration was given to variations in terms used and spellings of terms in different countries so that studies were not missed by the search strategy because of such variations. See Appendix 1 for a list of the search strategies used. Searching other resources Reference lists of retrieved articles and systematic reviews and meta-analyses published since the original Cochrane review were checked for any studies not identied by the electronic searches.
blinding of outcome assessment; incomplete outcome data; and selective outcome reporting (Higgins 2011). Assessments of risk of bias are provided in the Risk of bias table for each study. Dealing with missing data If there were multiple reports of the same study, the duplicate publications were scanned for additional data. Outcome results have been extracted at all follow-up points post-randomisation. Study authors were contacted where necessary to provide additional information. Assessment of heterogeneity
Data collection and analysis
Selection of studies The titles and abstracts of citations identied by the electronic searches prior to 2008 were examined for possible inclusion by two reviewers (RST & Philippa Davies) working independently. The titles and abstracts of citations identied by the electronic searches from 2008 onwards were examined for possible inclusion independently by two reviewers (BSH & LF). Full publications of potentially relevant studies were retrieved (and translated into English where required) and two reviewers (BSH & JMHC) then independently determined study eligibility using a standardized inclusion form. Any disagreements about study eligibility were resolved by discussion and, if necessary, a third reviewer (RST) was asked to arbitrate. Data extraction and management Data from included studies were extracted by one reviewer (BSH or JMHC) using standardised data extraction forms and checked by a second reviewer (JMHC or BSH). If data were presented numerically (in tables or text) and graphically (in gures), the numeric data were used because of possible measurement error when estimating from graphs. A second reviewer conrmed all numeric calculations and extractions from graphs or gures. Any discrepancies were resolved by consensus. Data on patient characteristics (e.g. age, sex, CHD diagnosis) and details of the intervention (including mode of exercise, duration, frequency and intensity), nature of usual care and length of followup were also extracted.
If there was signicant statistical heterogeneity (P-value <0.10) associated with an effect estimate, a random effects model was applied. This model provides a more conservative statistical comparison of the difference between intervention and control because a condence interval around the effect estimate is wider than a condence interval around a xed effect estimate. If a statistically signicant difference was still present using the random effects model, the xed effect pooled estimate and 95% CI have been reported because of the tendency of smaller trials, which are more susceptible to publication bias, to be over weighted with a random effects analysis (Heran 2008a; Heran 2008b). Assessment of reporting biases No language restrictions have been applied. Data synthesis Data have been processed in accordance with the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011). Data synthesis and analyses have been done using Review Manager 5.0 software and STATA version 10 (Stata Corp., College Station, Texas). Dichotomous outcomes for each comparison have been expressed as relative risks with 95% condence intervals (CI). Continuous outcome have been expressed as the mean (SD) change from baseline to follow-up. Otherwise, continuous outcomes have been pooled as weighted mean difference (WMD). If there was a statistically signicant absolute risk difference, the associated number needed to treat/harm was calculated. Subgroup analysis and investigation of heterogeneity Where possible, stratied meta-analysis (according to time of follow-up, 6 to12 months versus > 12 months) and meta-regression have been undertaken to explore heterogeneity and examine potential treatment effect modiers. We tested ve a priori hypotheses that there may be differences in the effect of exercise-based cardiac rehabilitation on total mortality, cardiovascular mortality,
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Assessment of risk of bias in included studies Two reviewers (BSH, JMHC) independently assessed the risk of bias in included studies using the Cochrane Collaborations recommended tool, which is a domain-based critical evaluation of the following domains: sequence generation; allocation concealment;
total MI, and revascularisation (CABG and PTCA) across particular subgroups: (1) CHD case mix (myocardial infarction-only trials versus other trials); (2) type of cardiac rehabilitation (exercise-only cardiac rehabilitation versus comprehensive cardiac rehabilitation); (3) dose of exercise intervention [dose = duration in weeks x number of sessions x number of sessions per week] (dose 1000 units versus dose < 1000 units); (4) follow-up period ( 12 months versus > 12 months); and (5) year of publication (before 1995 versus 1995 or later).
The funnel plot and the Egger test have been used to examine small study bias (Egger 1997).
RESULTS
Description of studies
See: Characteristics of included studies; Characteristics of excluded studies; Characteristics of studies awaiting classication; Characteristics of ongoing studies. Results of the search Our update cross-cardiac rehabilitation review electronic searches (to January 2008) yielded a total 11,561 titles plus 1802 titles from the update search (to December 2009). After reviewing the titles and abstracts, we retrieved 59 full-text articles for possible inclusion. A total of 30 papers were excluded: two had followup less than six months, 16 reported no useful outcomes, six had inappropriate randomisation, one had an inappropriate control, and ve were review articles. In addition, one study was awaiting classication and two were ongoing studies. Seventeen studies (26 publications) met the inclusion criteria and had extractable data to assess the effects of exercise-based cardiac rehabilitation compared with usual care on mortality and morbidity in patients with CHD (Figure 1).
Year of Publication
We included year of publication as a study level factor (pre versus post-1995) in order to assess the potential effect of a change in the standard of usual care over time, that is to reect when pharmacologic agents became established therapies for CHD.
Heterogeneity
Heterogeneity amongst included studies was explored qualitatively (by comparing the characteristics of included studies) and quantitatively (using the chi-squared test of heterogeneity and I2 statistic). Where appropriate, data from each study have been pooled using a xed effect model, except where substantial heterogeneity exists. We planned to pool the results for health-related quality of life using a standardised mean difference (SMD) but this was not possible due to the heterogeneity in outcome measures and methods of reporting ndings.
Figure 1. Study ow diagram
Included studies The original Cochrane review published in 2001 (Jolliffe 2001) included a total of 35 studies, of which ve studies were judged not to meet the revised inclusion criteria of this review update (see Excluded studies section). In addition to the 30 trials (55 publications) from the original Cochrane review that met the inclusion criteria of this update review (Andersen 1981; Bell 1998; Bengtsson 1983; Bertie 1992; Bethell 1990; Carlsson 1998; Carson 1982; DeBusk 1994; Engblom 1996; Erdman 1986; Fletcher 1994; Fridlund 1991; Haskell 1994; Heller 1993; Holmbck 1994; Kallio 1979; Leizorovicz 1991; Lewin 1992; Miller 1984; Oldridge 1991; Ornish 1990; Schuler 1992; Shaw 1981; Sivarajan 1982; Specchia 1996; Stern 1983; Vecchio 1981; Vermeulen 1983; WHO 1983; Wilhelmsen 1975), an additional 17 studies (26 publications) have been identied by the updated search and have met the revised inclusion criteria (Belardinelli 2001; Bck 2008; Dugmore 1999; Giallauria 2008; Hofman-Bang 1999; Kovoor 2006; La Rovere 2002; Manchanda 2000; Marchionni 2003; Seki 2003; Seki 2008; Sthle 1999; Toobert 2000; VHSG 2003; Yu 2003; Yu 2004; Zwisler 2008). Thus, a total of 47 studies reporting data for a total of 10,794 patients have been included in this review update. Details of the studies included in the review are listed in the Characteristics of included studies table. The study selection process is summarised in the PRISMA ow diagram shown in Figure 1. Although all exercise-based cardiac rehabilitation, 17 studies were judged to be exercise-only intervention trials and 29 were judged to be comprehensive cardiac rehabilitation (exercise plus psychosocial and/or educational interventions); one trial randomly assigned patients to both exercise-only cardiac rehabilitation and comprehensive cardiac rehabilitation (Sivarajan 1982). The majority of studies were (32 studies, 68%) undertaken in Europe, either as single or multicenter studies. Trial sample sizes varied widely from 28 to 2304, with a median intervention duration of three (range 0.25 to 30) months and a follow-up of 24 (range six to 120) months. Patients with myocardial infarction alone were recruited in 30 trials (64%); the remaining trials recruited either exclusively postrevascularisation patients (i.e., CABG and PTCA) or both groups of patients. The ages of patients in the trials ranged from 46 to 84 years. Although over half of the trials (28 studies, 60%) included women, on average women accounted for only 20% of the patients recruited.
while 17 reported on an exercise only intervention. In addition, one study randomised patients to a comprehensive programme, exercise only intervention or usual care (Sivarajan 1982). The exercise-based cardiac rehabilitation programmes differed considerably in duration (range 1-12 months), frequency (1-7 sessions/week), and session length (20-90 minutes/session). Most programmes involved the prescription of individually tailored exercise programmes, which makes it difcult to precisely quantify the amount of exercise undertaken. Most home based programmes included a short initial period of centre based intervention. Centre based programmes typically involved supervised exercise involving cycles, treadmills or weight training, while nearly all home based programmes were based on walking. Both intervention and control patients received usual care including medication, education and advice about diet and exercise, but control patients received no formal exercise training. Excluded studies Five studies that had been included in the original review failed to meet the revised inclusion criteria of this review update. Of these, four studies did not report outcomes relevant to this review (Ballantyne 1982; Carlsson 1997; Krachler 1997; Wosornu 1996) and one study was not randomised (Kentala 1972). For the updated search, 24 studies (25 publications) were excluded for reasons listed in the Characteristics of excluded studies table, with the most common reason being a failure to report any of the prespecied outcomes of this review update.
Risk of bias in included studies

Limited reporting of the methodology and outcome data in the published papers of the included trials precluded us, in most cases, from adequately performing a critical evaluation of the following domains: sequence generation; allocation concealment; blinding; incomplete outcome data; selective outcome reporting; and other sources of bias. Nevertheless, we attempted to assess the risk of bias for each of the 47 included studies given the available information in the published trial reports. Allocation Nearly all the trial publications simply reported that the trial was randomised but did not provide any details. A total of 8/47 (17%) studies (Andersen 1981; Bell 1998; Bethell 1990; Erdman 1986; Haskell 1994; Holmbck 1994; Wilhelmsen 1975; Zwisler 2008) reported details of appropriate generation of the random sequence and 7/47 (15%) studies (Bell 1998; Haskell 1994; Holmbck 1994; Kovoor 2006; Schuler 1992; VHSG 2003; Zwisler 2008) reported appropriate concealment of allocation.
Characteristics of included interventions
Twenty nine studies compared comprehensive programmes (that is, exercise plus education or psychological management, or both),
Blinding For exercise-based cardiac rehabilitation trials, it is not possible to blind patients and clinicians to the intervention. For the large majority of studies, insufcient information was provided to evaluate the blinding of assessors; only 4 of 47 (9%) studies (Fletcher 1994; Ornish 1990; Wilhelmsen 1975; Zwisler 2008) reported that outcome assessors were blind to group allocation.
thus in an intention to treat analysis, these then have been regarded as dropouts. Selective reporting A number of the included studies were not designed to assess treatment group differences in morbidity and mortality (as these were not the primary outcomes of these trials) and, therefore, may not have fully reported all clinical events that occurred during the follow-up period. All studies collecting validated health-related quality of life outcomes fully reported these outcomes. Other potential sources of bias
Incomplete outcome data Losses to follow-up and drop out were relatively high, ranging from 21% to 48% in 12 trials. Follow-up of 80% or more was achieved in 33/47 (70%) studies (Andersen 1981; Belardinelli 2001; Bell 1998; Bethell 1990; Bck 2008; Carlsson 1998; Dugmore 1999; Engblom 1996; Giallauria 2008; Haskell 1994; Heller 1993; Holmbck 1994; Kallio 1979; Kovoor 2006; La Rovere 2002; Leizorovicz 1991; Lewin 1992; Manchanda 2000; Marchionni 2003; Miller 1984; Oldridge 1991; Schuler 1992; Seki 2003; Shaw 1981; Specchia 1996; Stern 1983; Sthle 1999; Toobert 2000; Vermeulen 1983; VHSG 2003; Wilhelmsen 1975; Yu 2003; Zwisler 2008). Furthermore, reasons for loss to follow and dropout were often not reported. Two trials (Seki 2008; WHO 1983) did not report information on losses to follow-up. Several trials have excluded signicant numbers of patients post-randomisation, and
Publication bias
In order to test for the possibility of publication bias, the funnel plots were created for all-cause mortality, cardiovascular mortality, recurrent MI, and revascularisation (CABG and PTCA). There was no evidence of funnel plot asymmetry or signicant Egger tests for all-cause mortality, cardiovascular mortality and revascularisation (CABG and PTCA). However, the funnel plot of recurrent MI suggests asymmetry and the Egger test was statistically signicant (P = 0.019), which appears to be due to an absence of negative-result trials of small to medium size (Figure 2).
Figure 2. Funnel plot of exercise-based rehabilitation versus usual care for fatal and/or nonfatal MI
Effects of interventions
Clinical Events
follow-up. There was no evidence of statistical heterogeneity across trials for either total or cardiovascular mortality.
Morbidity Mortality
Thirty (N = 8971) of the included studies reported total mortality (Analysis 1.1); two trials reported both follow-up to 12 months and longer than 12 months (Wilhelmsen 1975; WHO 1983). In studies reporting follow-up longer than 12 months, compared with control, total mortality was reduced with exercise-based cardiac rehabilitation (RR 0.87 [95% CI 0.75, 0.99]). There was no signicant difference in total mortality up to 12 months followup. Nineteen (N = 6583) of included studies reported cardiovascular mortality (Analysis 1.2); one trial reported both follow-up to 12 months and longer than 12 months (WHO 1983). In studies reporting follow-up longer than 12 months, compared to control, cardiovascular mortality was reduced with exercise-based cardiac rehabilitation (RR 0.74 [95% CI 0.63, 0.87]). There was no signicant difference in cardiovascular mortality up to 12 months
Twenty-ve (N = 7294), 22 (N = 4392), and 11 (N = 2241) of the included studies reported total MI, CABG or PTCA, respectively (Analysis 1.3; Analysis 1.4; Analysis 1.5); follow-up to 12 months and longer than 12 months was reported by two studies for MI (Haskell 1994; WHO 1983), one study for CABG (Sthle 1999) and two studies for PTCA (Haskell 1994; Sthle 1999). There was no statistically signicant difference between exercise-based cardiac rehabilitation and usual care for these outcome measures. The pooled risk ratios for total MI, CABG and PTCA were 0.92 (95% CI 0.70, 1.22), 0.91 (95% CI 0.67, 1.24) and 1.02 (95% CI 0.69, 1.50), respectively, up to 12 months follow-up. In studies reporting follow-up longer than 12-months, the pooled risk ratios for total MI, CABG and PTCA were 0.97 (95% CI 0.82, 1.15), 0.93 (95% CI 0.68, 1.27) and 0.89 (95% CI 0.66, 1.19) respectively. There was no evidence of statistical heterogeneity across trials for any of the morbidity outcomes.
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Hospitalisations
Ten (N = 2379) of the included studies reported hospital admissions; one study reported both follow-up to 12 months and longer than 12 months (Hofman-Bang 1999). In studies reporting up to 12 months follow-up, total readmissions were reduced with exercise-based cardiac rehabilitation compared with usual care (RR 0.69, 95% CI 0.51, 0.93; Analysis 1.6). There was no signicant difference in total hospitalisations in studies with follow-up longer than 12 months.
comprehensive cardiac rehabilitation); dose of exercise intervention (calculated as the number of weeks, multiplied by the number of sessions per week, multiplied by the duration of sessions in hours); follow-up period ( 12 months versus > 12 months); and publication date (before 1995 versus 1995 or later). No statistically signicant associations were seen in any of these analyses (Table 3, Table 4, Table 5, Table 6, Table 7).
DISCUSSION
Health-related quality of life Ten trials assessed health-related quality of life using a range of validated disease-specic (e.g. QLMI) and generic (e.g. Short-form 36) outcome measures (Table 1). Given both the heterogeneity in outcome measures and methods of reporting ndings, a metaanalysis was not undertaken. Although most trials demonstrated an improvement in baseline quality of life following exercise-based cardiac rehabilitation, a within group improvement was also often reported in control patients. Only in seven out of 10 trials was there evidence of a signicantly higher level of quality of life with exercise-based cardiac rehabilitation than control at follow-up (Belardinelli 2001; Dugmore 1999; Sivarajan 1982; Yu 2004).
Summary of main results

This updated systematic review of exercise-based cardiac rehabilitation has allowed analysis of an increased number of patients from an additional 17 studies published from 2000 to 2009. A total of 47 RCTs, with 10,794 patients, have now been included. In accord with the original Cochrane review and previous metaanalyses (Clark 2005; Jolliffe 2001; OConnor 1989; Oldridge 1988) a reduction in both total and cardiac mortality was observed in CHD patients randomised to exercise-based rehabilitation. However, this updated review shows that this mortality benet is limited to studies with a follow-up of greater than 12 months. We also found that with exercise the rate of hospital readmissions may be reduced in studies up to 12 months follow-up (based on 4 trials with 54/254 versus 73/225 events), but not in longer term follow-up. There was no difference between exercise-based cardiac rehabilitation and usual care groups in the risk of recurrent myocardial infarction or revascularization at any duration of followup. This reduction in total and cardiovascular mortality with exercise therapy appears consistent across a number of CHD groups (e.g., post-MI, post-revascularisation), as well as a range of strategies for delivery of the exercise-based intervention. We compared trials that assessed exercise therapy alone with exercise in combination with educational and psychological co-interventions and there appears to be no difference in mortality effect. In addition, there was no difference in mortality effect by exercise dose a composite measure based on the overall duration of the exercise program plus the intensity, frequency, and length of exercise sessions. The mechanism for reduced cardiovascular mortality in patients who have received exercise-based cardiac rehabilitation is not clear, but may be due to improved myocardial revascularisation, protection against fatal dysrhythmias, improved cardiovascular risk factor prole, improved cardiovascular tness, or increased patient surveillance (Oldridge 1988; Taylor 2006). There were insufcient data to denitely denitely conclude that exercise-based cardiac rehabilitation improves health-related quality of life compared to control. Only 10 of included trials reported outcomes based on a validated health-related quality of life measure. Furthermore, only three of these 10 trials randomised more
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Costs Three of the included studies reported limited data on costs per patient (Kovoor 2006; Marchionni 2003; Yu 2004). These results are summarised in Table 2. It was not possible to compare the costs directly across studies due to differences in currencies and the timing of studies. In two of the three studies the total healthcare costs associated with exercise-based cardiac rehabilitation and usual care were not statistically signicantly different. In Marchionni 2003, the total healthcare costs associated with exercise-based cardiac rehabilitation were higher ($4839 more per patient) than usual care. Only Oldridge 1991 evaluated the cost-effectiveness of exercisebased cardiac rehabilitation in post-MI patients by combining cost information with time trade-off measures of health-related quality of life and data on mortality derived from a 1989 meta-analysis (OConnor 1989). Based on their analysis, the authors concluded that rehabilitation was an efcient use of health-care resources and may be economically justied (Oldridge 1993).
Meta regression Predictors of all-cause mortality, cardiovascular mortality, recurrent MI, and revascularisation (CABG and PTCA) were examined using univariate meta-regression. Covariates dened a priori included: CHD case mix (myocardial infarction-only trials versus other trials); type of cardiac rehabilitation (exercise-only versus
than 250 patients; thus, providing relatively adequate power (80% and 5% alpha) to detect a modest difference (standardised effect size of 0.25) between exercise therapy and usual care. Heterogeneity of health-related quality of life outcome measures and their reporting precluded us from quantitatively pooling the available data across trials. Generic health-related quality of life measures that lack sensitivity to change with cardiac treatment, particularly in comparison with disease-specic measures, were used in nearly all the trials (Oldridge 2003; Taylor 1998). All participants in the included studies had documented CHD, the majority of the participants having suffered an MI. Some participants had documented CHD having suffered angina or undergone coronary angiography, while others had undergone CABG. We have combined these different patient groups as there are insufcient data at present to stratify trials by type of CHD. The number of women participants was low and few studies mentioned the ethnic origin of their participants. The mean age of the participants was 56 years. Although most studies had an upper age limit of at least 65 years of age, this is not reected in the mean age of the participants. The majority of the studies had exclusion criteria that would have excluded those participants who had co-morbidity, or heart failure. In some studies this may have accounted for up to 60% of the patients considered for the trial, and certainly the older patients would be more likely to be affected.
AUTHORS CONCLUSIONS Implications for practice

In medium to longer term (i.e. 12 or more months follow-up) exercise-based cardiac rehabilitation is effective in reducing overall and cardiovascular mortality and appears to reduce the risk of hospital admissions in the shorter-term (< 12 months follow-up) in patients with CHD. The available evidence does not demonstrate a reduction in the risk of total MI, CABG or PTCA with exercisebased cardiac rehabilitation as compared to usual care at any duration of follow-up. Exercise-based cardiac rehabilitation should be recommended for patients similar to those included in the randomised controlled trials - predominantly lower risk younger men who had suffered myocardial infarction or are post-revascularisation. It is a question of judgement whether evidence is sufcient to under-represented groups, particularly angina pectoris and higher risk CHD patients and those with major co-morbidities. There appears to be little to choose between exercise only or in combination with psychosocial or educational cardiac rehabilitation interventions. In the absence of denitive cost-effectiveness comparing these two approaches to exercise-based cardiac rehabilitation it would be rational to use cost considerations to determine practise.
Implications for research

In spite of inclusion of recent trial evidence including more postrevascularisation and female patients, the population of CHD patients studied in this review update remains predominately low risk middle-aged males following MI or PTCA. There has been little identication of the ethnic origin of the participants. It is possible that patients who would have beneted most from exercise-based cardiac rehabilitation were excluded from the trials e.g. those of older age or those with co-morbidity. Therefore, well-designed, and adequately reported RCTs in groups of CHD patients more representative of usual clinical practice are still needed. These trials should include validated health-related quality of life outcome measures, need to explicitly report clinical events including hospital admission, and assess costs and cost-effectiveness.
Quality of the evidence

We found no evidence of publication bias for total mortality, CV mortality, CABG or PTCA. There was evidence of small study bias for total MI. As with the original Cochrane review, this update review has revealed limitations in the available RCT evidence, most notably the poor reporting of methodology and results in many trial publications (Jolliffe 2001). The method of randomization, allocation concealment, or blinding of outcomes assessment was rarely described. Although the quality of reporting tends to be poorer for older studies, it does not appear to have appreciably improved over the last decade. Furthermore, incomplete outcome data (primarily due to losses to follow-up or dropouts) were insufciently addressed in most trials. Losses to follow-up were relatively high across trials (approximately one third of trials reported a greater than 20% loss to follow-up) but reasons for dropout were often not reported. Several trials excluded signicant numbers of patients post-randomisation, and thus in an intention-to-treat analysis, these patients have been regarded as dropouts. This may be partly explained by the fact that the majority of trials were not designed to assess treatment group differences in mortality and morbidity but instead surrogate measures of treatment efcacy, such as exercise capacity or lipid levels.
ACKNOWLEDGEMENTS
We would like to thank Lambert Felix and Philippa Davies for examining the titles and abstracts of citations identied by the electronic searches for possible inclusion. We would also like to thank Sue Whiffen for her administrative assistance and Nizar Abazid, Ela Gohil, Ellen Ingham, Cornelia Junghans, Joey Kwong, Dan Manzari, Fenicia Vescio, and Gavin Wong for their translation services. We would like to thank all the authors who provided additional information about their trials.
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REFERENCES
References to studies included in this review

Andersen 1981 {published data only} Andersen GS, Christiansen P, Madsen S, Schmidt G. The value of regular, supervised physical training after acute myocardial infarction [Vaerdien af regelmaessig og overvget fysisk traening efter akut myokardieinfarkt.]. Ugeskrift for Laeger 1981;143(45):29525. Belardinelli 2001 {published data only} Belardinelli R, Paolini I, Cianci G, Piva R, Georgiou D, Purcaro A. Exercise training intervention after coronary angioplasty: The ETICA Trial. Journal of the American College of Cardiology 2001;37(7):1891900. Bell 1998 {unpublished data only} Bell JM. A comparison of a multi-disciplinary home based cardiac rehabilitation programme with comprehensive conventional rehabilitation in post-myocardial infarction patients. PhD Thesis, University of London 1998. Bengtsson 1983 {published data only} Bengtsson K. Rehabilitation after myocardial infarction. Scandinavian Journal of Rehabilitation Medicine 1983;15(1): 19. Bertie 1992 {published data only} Bertie J, King A, Reed N, Marshall AJ, Ricketts C. Benets and weaknesses of a cardiac rehabilitation programme. Journal of the Royal College of Physicians of London 1992;26 (2):14751. Bethell 1990 {published and unpublished data} Bethell HJN, Mullee MA. A controlled trial of community based coronary rehabilitation. British Heart Journal 1990; 64(6):3705. Bck 2008 {published data only} Bck M, Wennerblom B, Wittboldt S, Cider A. Effects of high frequency exercise in patients before and after elective percutaneous coronary intervention. European Journal of Cardiovascular Nursing 2008;7(4):30713. Carlsson 1998 {published data only} Carlsson R. Serum cholesterol, lifestyle, working capacity and quality of life in patients with coronary artery disease. Experiences from a hospital-based secondary prevention programme. Scandinavian Cardiovascular Journal. Supplement 1998;50:120. Carson 1982 {published data only} Carson P, Phillips R, Lloyd M, Tucker H, Neophytou M, Buch NJ, et al.Exercise after myocardial infarction: a controlled trial. Journal of the Royal College of Physicians of London 1982;16(3):14751. DeBusk 1994 {published data only} DeBusk RF, Miller NH, Superko HR, Dennis CA, Thomas RJ, Lew HT, et al.A case management system for
coronary risk factor modication following acute myocardial infarction. Annals of Internal Medicine 1994;120(9):7219. Taylor CB, Miller NH, Smith PM, DeBusk RF. The effect of a home-based, case-managed, multifactorial risk-reduction program on reducing psychological distress in patients with cardiovascular disease. Journal of Cardiopulmonary Rehabilitation 1997;17(3):15762. Dugmore 1999 {published data only} Dugmore LD, Tipson RJ, Phillips MH, Flint EJ, Stentiford NH, Bone MF, et al.Changes in cardiorespiratory tness, psychological wellbeing, quality of life, and vocational status following a 12 month cardiac exercise rehabilitation programme. Heart 1999;81(4):35966. Engblom 1996 {published data only} Engblom E, Hamalainen H, Lind J, Mattlar CE, Ollila S, Kallio V, et al.Quality of life during rehabilitation after coronary bypass surgery. Quality of Life Research 1992;1: 16775. [MEDLINE: 93244729] Engblom E, Hietanen EK, Hamalainen H, Kallio V, Inberg M, Knuts L-R. Exercise habits and physical performance during comprehensive rehabilitation after coronary artery bypass surgery. European Heart Journal 1992;13:10539. [MEDLINE: 92209581] Engblom E, Korpilahti K, Hamalainen H, Puukka P, Ronnemaa T. Effects of ve years of cardiac rehabilitation after coronary artery bypass grafting on coronary risk factors. American Journal of Cardiology 1996;78:142831. [MEDLINE: 97125341] Engblom E, Korpilahti K, Hamalainen H, Ronnemaa T, Puukka P. Quality of life and return to work 5 years after coronary artery bypass surgery. Journal of Cardiopulmonary Rehabilitation 1997;17:2936. [MEDLINE: 97193477] Engblom E, Rnnemaa T, Hmlinen H, Kallio V, Vnttinen, Knuts LR. Coronary heart disease risk factors before and after bypass surgery: results of a controlled trial on multifactorial rehabilitation. European Heart Journal 1992;13(2):2327. [MEDLINE: 92209581] Erdman 1986 {published data only} Erdman RAM, Duivenvoorden HJ, Verhage F, Kazemier M, Hugenholtz PG. Predictability of benecial effects in cardiac rehabilitation: A randomized clinical trial of psychosocial variables. Journal of Cardiopulmonary Rehabilitation 1986;6 (6):20613. Fletcher 1994 {published data only} Fletcher BJ, Dunbar SB, Felner JM, Jensen BE, Almon L, Cotsonis G, et al.Exercise testing and training in physically disabled men with clinical evidence of coronary artery disease. American Journal of Cardiology 1994;73(2):1704. Fridlund 1991 {published data only} Fridlund B, Hgstedt B, Lidell E, Larsson PA. Recovery after myocardial infarction: Effects of a caring rehabilitation
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programme. Scandinavian Journal of Caring Sciences 1991;5 (1):2332. Fridlund B, Lidell E, Larsson PA. A caring perspective on rehabilitation after myocardial infarction: A theoretical framework and a suggestion for a rehabilitation programme. Scandinavian Journal of Caring Sciences 1989;3(3):12935. Fridlund B, Pihilgren C, Wannestig LB. A supportive educative caring rehabilitation programme: improvements of physical health after myocardial infarction. Journal of Clinical Nursing 1992;1:1416. Lidell E, Fridlund B. Long-term effects of a comprehensive rehabilitation programme after myocardial infarction. Scandinavian Journal of Caring Sciences 1996;10:6774. Giallauria 2008 {published data only} Giallauria F, Cirillo P, Lucci R, Pacileo M, De Lorenzo A, DAgostino M, et al.Left ventricular remodelling in patients with moderate systolic dysfunction after myocardial infarction: favourable effects of exercise training and predictive role of N-terminal pro-brain natriuretic peptide. European Journal of Cardiovascular Prevention and Rehabilitation 2008;15(1):1138. Haskell 1994 {published data only} Haskell WL, Alderman EL, Fair JM, Maron DJ, Mackey SF, Superko HR, et al.Effects of intensive multiple risk factor reduction on coronary atherosclerosis and clinical cardiac events in men and women with coronary artery disease: The Stanford Coronary Risk Intervention Project (SCRIP). Circulation 1994;89(3):97590. Heller 1993 {published data only} Heller RF, Knapp JC, Valenti LA, Dobson AJ. Secondary prevention after acute myocardial infarction. American Journal of Cardiology 1993;72(11):75962. Hofman-Bang 1999 {published data only} Hofman-Bang C, Lisspers J, Nordlander R, Nygren , Sundin , hman A, et al.Two-year results of a controlled study of residential rehabilitation for patients treated with percutaneous transluminal coronary angioplasty. A randomized study of a multifactorial programme. European Heart Journal 1999;20(20):146574. Lisspers J, Sundin , Hofman-Bang C, Nordlander R, Nygren , Rydn L, et al.Behavioral effects of a comprehensive multifactorial program for lifestyle change after percutaneous transluminal coronary angioplasty: A prospective randomized, controlled study. Journal of Psychosomatic Research 1999;46(2):14354. Lisspers J, Sundin , hman A, Hofman-Bang C, Rydn L, Nygren . Long-term effects of lifestyle behavior change in coronary artery disease: Effects on recurrent coronary events after percutaneous coronary intervention. Health Psychology 2005;24(1):418. Holmbck 1994 {published data only} Holmbck AM, Swe U, Fagher B. Training after myocardial infarction: Lack of long-term effects on physical capacity and psychological variables. Archives of Physical Medical and Rehabilitation 1994;75(5):5514.
Kallio 1979 {published data only} Kallio V, Hmlinen H, Hakkila J, Luurila OJ. Reduction in sudden deaths by a multifactorial intervention programme after acute myocardial infarction. Lancet 1979; 2(8152):10914. Kovoor 2006 {published data only} Kovoor P, Lee AKY, Carrozzi F, Wiseman V, Byth K, Zecchin R, et al.Return to full normal activities including work at two weeks after acute myocardial infarction. American Journal of Cardiology 2006;97(7):9528. La Rovere 2002 {published data only} La Rovere MT, Bersano C, Gnemmi M, Specchia G, Schwartz PJ. Exercise-induced increase in baroreex sensitivity predicts improved prognosis after myocardial infarction. Circulation 2002;106(8):9459. Leizorovicz 1991 {published data only} Leizorovicz A, Saint-Pierre A, Vasselon C, Boissel JP. Comparison of a rehabilitation programme, a counselling programme and usual care after an acute myocardial infarction: Results of a long-term randomized trial. P.RE.COR. Group. European Heart Journal 1991;12(5): 6126. Lewin 1992 {published data only} Lewin B, Robertson IH, Cay EL, Irving JB, Campbell M. Effects of self-help post-myocardial infarction rehabilitation on psychological adjustment and use of health services. Lancet 1992;339(8800):103640. Manchanda 2000 {published data only} Manchanda SC, Narang R, Reddy KS, Sachdeva U, Prabhakaran D, Dharmanand S, et al.Retardation of coronary atherosclerosis with yoga lifestyle intervention. Journal of the Association of Physicians of India 2000;48(7): 68794. Marchionni 2003 {published data only} Marchionni N, Fattirolli F, Fumagalli S, Oldridge N, Del Lungo F, Morosi L, et al.Improved exercise tolerance and quality of life with cardiac rehabilitation of older patients after myocardial infarction: Results of a randomized, controlled trial. Circulation 2003;107(17):22016. Miller 1984 {published data only} DeBusk RF, Haskell WL, Miller NH, Berra K, Taylor CB, Berger WE, et al.Medically directed at-home rehabilitation soon after clinically uncomplicated acute myocardial infarction: a new model for patient care. American Journal of Cardiology 1985;55(4):2517. Miller NH, Haskell WL, Berra K, DeBusk RF. Home versus group exercise training for increasing functional capacity after myocardial infarction. Circulation 1984;70 (4):6459. Taylor CB, Houston-Miller N, Ahn DK, Haskell WL, DeBusk RF. The effects of exercise training programs on psychosocial improvement in uncomplicated postmyocardial infarction patients. Journal of Psychosomatic Research 1986; 30(5):5817. Taylor CB, Houston-Miller N, Haskell WL, DeBusk RF. Smoking cessation after acute myocardial infarction: The
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effects of exercise training. Addictive Behaviors 1988;13(4): 3315. Oldridge 1991 {published and unpublished data} Oldridge N, Guyatt G, Jones N, Crowe J, Singer J, Feeny D, et al.Effects on quality of life with comprehensive rehabilitation after acute myocardial infarction. American Journal of Cardiology 1991;67(13):10849. Oldridge N, Streiner D, Hoffmann R, Guyatt G. Prole of mood states and cardiac rehabilitation after acute myocardial infarction. Medicine and Science in Sports and Exercise 1995; 27(6):9005. Ornish 1990 {published data only} Ornish D, Brown SE, Scherwitz LW, Billings JH, Armstrong WT, Ports TA, et al.Can lifestyle changes reverse coronary heart disease? The Lifestyle Heart Trial. Lancet 1990;336(8708):12933. Ornish D, Scherwitz LW, Billings JH, Brown SE, Gould KL, Merritt TA, et al.Intensive lifestyle changes for reversal of coronary heart disease. JAMA 1998;280(23):20017. Pischke CR, Scherwitz L, Weidner G, Ornish D. Longterm effects of lifestyle changes on well-being and cardiac variables among coronary heart disease patients. Health Psychology 2008;27(5):58492. Schuler 1992 {published data only} Hambrecht R, Niebauer J, Marburger C, Grunze M, Kalberer B, Hauer K, et al.Various intensities of leisure time physical activity in patients with coronary artery disease: Effects on cardiorespiratory tness and progression of coronary atherosclerotic lesions. Journal of the American College of Cardiology 1993;22(2):46877. Niebauer J, Hambrecht R, Marburger C, Hauer K, Velich T, von Hodenberg E, et al.Impact of intensive physical exercise and low-fat diet on collateral vessel formation in stable angina pectoris and angiographically conrmed coronary artery disease. American Journal of Cardiology 1995;76(11): 7715. Niebauer J, Hambrecht R, Velich T, Hauer K, Marburger C, Kalberer B, et al.Attenuated progression of coronary artery disease after 6 years of multifactorial risk intervention: role of physical exercise. Circulation 1997;96(8):253441. Niebauer J, Hambrecht R, Velich T, Marburger C, Hauer K, Kreuzer J, et al.Predictive value of lipid prole for salutary coronary angiographic changes in patients on a low-fat diet and physical exercise program. American Journal of Cardiology 1996;78(2):1637. Nikolaus T, Schlierf G, Vogel G, Schuler G, Wagner I. Treatment of coronary heart disease with diet and exercise: problems of compliance. Annals of Nutrition and Metabolism 1991;35:17. Schuler G, Hambrecht R, Schlierf G, Niebauer J, Hauer K, Neumann J, et al.Regular physical exercise and lowfat diet. Effects on progression of coronary artery disease. Circulation 1992;86(1):111. Seki 2003 {published data only} Seki E, Watanabe Y, Sunayama S, Iwama Y, Shimada K, Kawakami K, et al.Effects of phase III cardiac rehabilitation programs on health-related quality of life in elderly
patients with coronary artery disease: Juntendo Cardiac Rehabilitation Program (J-CARP). Circulation Journal 2003;67(1):737. Seki 2008 {published data only} Seki E, Watanabe Y, Shimada K, Sunayama S, Onishi T, Kawakami K, et al.Effects of a phase III cardiac rehabilitation program on physical status and lipid proles in elderly patients with coronary artery disease: Juntendo Cardiac Rehabilitation Program (J-CARP). Circulation Journal 2008;72(8):12304. Shaw 1981 {published data only} Naughton J. The National Exercise and Heart Disease Project. The pre-randomization exercise program. Report number 2. Cardiology 1978;63(6):35267. Shaw LW. Effects of a prescribed supervised exercise program on mortality and cardiovascular morbidity in patients after a myocardial infarction. The National Exercise and Heart Disease Project. American Journal of Cardiology 1981;48(1):3946. Stern MJ, Cleary P. The National Exercise and Heart Disease Project: Long-term psychosocial outcome. Archives of Internal Medicine 1982;142(6):10937. Sivarajan 1982 {published data only} Ott CR, Sivarajan ES, Newton KM, Almes MJ, Bruce RA, Bergner M, et al.A controlled randomized study of early cardiac rehabilitation: The sickness impact prole as an assessment tool. Heart & Lung 1983;12(2):16270. Sivarajan ES, Bruce RA, Almes MJ, Green B, Belanger L, Lindskog BD, et al.In-hospital exercise after myocardial infarction does not improve treadmill performance. New England Journal of Medicine 1981;305(7):35762. Sivarajan ES, Bruce RA, Lindskog BD, Almes MJ, Belanger L, Green B. Treadmill test responses to an early exercise program after myocardial infarction: A randomized study. Circulation 1982;65(7):14208. Sivarajan ES, Newton KM, Almes MJ, Kempf TM, Manseld LW, Bruce RA. Limited effects of outpatient teaching and counselling after myocardial infarction: A controlled study. Heart & Lung 1983;12(1):6573. Specchia 1996 {published data only} Specchia G, De Servi S, Scir A, Assandri J, Berzuini C, Angoli L, et al.Interaction between exercise training and ejection fraction in predicting prognosis after a rst myocardial infarction. Circulation 1996;94(5):97882. Stern 1983 {published data only} Stern MJ, Gorman PA, Kaslow L. The group counseling v exercise therapy study. A controlled intervention with subjects following myocardial infarction. Archives of Internal Medicine 1983;143(9):171925. Sthle 1999 {published data only} Hage C, Mattsson E, Sthle A. Long term effects of exercise training on physical activity level and quality of life in elderly coronary patients - a three- to six-year follow-up. Physiotherapy Research International 2003;8(1):1322. Sthle A, Lindquist I, Mattsson E. Important factors for physical activity among elderly patients one year after
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an acute myocardial infarction. Scandinavian Journal of Rehabilitation Medicine 2000;32(3):1116. Sthle A, Mattsson E, Rydn L, Unden AL, Nordlander R. Improved physical tness and quality of life following training of elderly patients after acute coronary events. A 1 year follow-up randomized controlled study. European Heart Journal 1999;20(20):147584. Sthle A, Nordlander R, Rydn L, Mattsson E. Effects of organized aerobic group training in elderly patients discharged after an acute coronary syndrome. A randomized controlled study.. Scandinavian Journal of Rehabilitation Medicine 1999;31(2):1017. Sthle A, Tollbck A. Effects of aerobic group training on exercise capacity, muscular endurance and recovery in elderly patients with recent coronary events: A randomized, controlled study. Advances in Physiotherapy 2001;3:2937. Toobert 2000 {published data only} Toobert DJ, Glasgow RE, Nettekoven LA, Brown JE. Behavioral and psychosocial effects of intensive lifestyle management for women with coronary heart disease. Patient Education and Counseling 1998;35(3):17788. Toobert DJ, Glasgow RE, Radcliffe JL. Physiologic and related behavioral outcomes from the Womens Lifestyle Heart Trial. Toobert DJ. Glasgow RE. Radcliffe JL.. Annals of Behavioral Medicine 2000;22(1):19. Vecchio 1981 {published data only} Vecchio C, Cobelli F, Opasich C, Assandri J, Poggi G, Griffo R. Early functional evaluation and physical rehabilitation in patients with wide myocardial infarction [Valutazione funzionale precoce e riabilitazione sica nei pazienti con infarto miocardico esteso]. Giornale Italiano di Cardiologia 1981;11:41929. Vermeulen 1983 {published data only} Vermeulen A, Lie KI, Durrer D. Effects of cardiac rehabilitation after myocardial infarction: changes in coronary risk factors and long-term prognosis. American Heart Journal 1983;105(5):798801. VHSG 2003 {published data only} Vestfold Heartcare Study Group. Inuence on lifestyle measures and ve-year coronary risk by a comprehensive lifestyle intervention programme in patients with coronary heart disease. European Journal of Cardiovascular Prevention and Rehabilitation 2003;10(6):42937. WHO 1983 {published data only} World Health Organisation. Rehabilitation and comprehensive secondary prevention after acute myocardial infarction. EURO Reports and Studies 84 1983. Wilhelmsen 1975 {published data only} Sanne H. Exercise tolerance and physical training of nonselected patients after myocardial infarction. Acta Medica Scandinavica 1973;Supplementum 551:1124. Wilhelmsen L, Sanne H, Elmfeldt D, Grimby G, Tibblin G, Wedel H. A controlled trial of physical training after myocardial infarction. Effects on risk factors, nonfatal reinfarction, and death. Preventive Medicine 1975;4(4): 491508.
Yu 2003 {published data only} Yu CM, Li LS, Ho HH, Lau CP. Long-term changes in exercise capacity, quality of life, body anthropometry, and lipid proles after a cardiac rehabilitation program in obese patients with coronary heart disease. American Journal of Cardiology 2003;91(3):3215. Yu 2004 {published data only} Yu C, Li L, Lam M, Siu D, Miu R, Lau C. Effect of a cardiac rehabilitation program on left ventricular diastolic function and its relationship to exercise capacity in patients with coronary heart disease: experience from a randomized, controlled study. American Heart Journal 2004;147(5):e24. Yu CM, Lau CP, Chau J, McGhee S, Kong SL, Cheung BM, et al.A short course of cardiac rehabilitation program is highly cost effective in improving long-term quality of life in patients with recent myocardial infarction or percutaneous coronary intervention. Archives of Physical Medicine and Rehabilitation 2004;85(12):191522. Zwisler 2008 {published and unpublished data} Kruse M, Hochstrasser S, Zwisler AD, Kjellberg J. Comprehensive cardiac rehabilitation: A cost assessment based on a randomized clinical trial. International Journal of Technology Assessment in Health Care 2006;22(4):47883. Zwisler AD, Soja AM, Rasmussen S, Frederiksen M, Abedini S, Appel J, et al.Hospital-based comprehensive cardiac rehabilitation versus usual care among patients with congestive heart failure, ischemic heart disease, or high risk of ischemic heart disease: 12-month results of a randomized clinical trial. American Heart Journal 2008;155 (6):110613.
References to studies excluded from this review

Agren 1989 {published data only} Agren B, Olin C, Castenfors J, Nilsson-Ehle P. Improvements of the lipoprotein prole after coronary bypass surgery: additional effects of an exercise training program. European Heart Journal 1989;10(5):4518. Aronov 2006 {published data only} Aronov DM, Krasnitski VB, Bubnova MG, Posdniakov IuM, Ioseliani DV, Shchegolkov AN, et al.Exercise in outpatient complex rehabilitation and secondary prophylaxis in patients with ischemic heart disease after acute coronary events (a cooperative trial in Russia). Terapevticheskii Arkhiv 2006;78(9):338. Ballantyne 1982 {published data only} Ballantyne FC, Clark RS, Simpson HS, Ballantyne D. The effect of moderate physical exercise on the plasma lipoprotein subfractions of male survivors of myocardial infarction. Circulation 1982;65(5):9138. Belardinelli 2007 {published data only} Belardinelli R, Lacalaprice F, Piccoli G, Iacobone G, Piva R. Long-term benets of cardiac rehabilitation in patients with incomplete revascularization: 5-year follow-up. Circulation 2007;116(16):3543.
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Bettencourt 2005 {published data only} Bettencourt N, Dias C, Mateus P, Sampaio F, Santos L, Adao L, et al.Impact of cardiac rehabilitation on quality of life and depression after acute coronary syndrome [Impacto da reabilitacao cardiaca na qualidadedevida e sintomatologia depressiva apos sindroma coronaria aguda]. Revista Portuguesa de Cardiologia 2005;24(5):68796. Bjrntorp 1972 {published data only} Bjrntorp, Berchtold P, Grimby G, Lindholm B, Sanne H, Tibblin G, et al.Effects of physical training on glucose tolerance, plasma insulin and lipids and on body composition in men after myocardial infarction. Acta Medica Scandinavica 1972;192(1-6):43943. Blumenthal 1997 {published data only} Blumenthal JA, Wei J, Babyak MA, Krantz DS, Frid DJ, Coleman RE, et al.Stress management and exercise training in cardiac patients with myocardial ischemia: effects on prognosis and evaluation of mechanisms. Archives of Internal Medicine 1997;157(19):221323. Br 1992 {published data only} Br FW, Hoppener P, Diederiks J, Vonken H, Bekkers J, Hoofd W, Appels A, et al.Cardiac rehabilitation contributes to the restoration of leisure and social activities. Journal of Cardiopulmonary Rehabilitation 1992;12(2):11725. Carlsson 1997 {published data only} Carlsson R, Lindberg G, Westin L, Israelsson B. Inuence of coronary nursing management follow up on lifestyle after acute myocardial infarction. Heart 1997;77(3):2569. Gao 2007 {published data only} Gao WG, Hu DY, Ma WL, Tang CZ, Li J, Hasimu B, et al.Effect of health management on the rehabilitation of patients undergoing coronary artery bypass graft. Journal of Clinical Rehabilitative Tissue Engineering Research 2007;11 (25):48748. Giannuzzi 2008 {published data only} Giannuzzi P, Temporelli PL, Marchioli R, Maggioni AP, Balestroni G, Ceci V, et al.Global secondary prevention strategies to limit event recurrence after myocardial infarction: Results of the GOSPEL study, a multicenter, randomized controlled trial from the Italian Cardiac Rehabilitation Network. Archives of Internal Medicine 2008; 168(20):2194204. Gielen 2003 {published data only} Gielen S, Erbs S, Linke A, Mobius-Winkler S, Schuler G, Hambrecht R. Home-based versus hospital-based exercise programs in patients with coronary artery disease: effects on coronary vasomotion. American Heart Journal 2003;145 (1):e3. Heldal 2000 {published data only} Heldal M, Sire S, Dale J. Randomised training after myocardial infarction: Short and long-term effects of exercise training after myocardial infarction in patients on beta-blocker treatment. A randomized, controlled study. Scandinavian Cardiovascular Journal 2000;34(1):5964.
Higgins 2001 {published data only} Higgins HC, Hayes RL, McKenna KT. Rehabilitation outcomes following percutaneous coronary interventions (PCI). Patient Education and Counseling 2001;43(3): 21930. Jiang 2007 {published data only} Jiang X, Sit JW, Wong TKS. A nurse-led cardiac rehabilitation programme improves health behaviours and cardiac physiological risk parameters: evidence from Chengdu, China. Journal of Clinical Nursing 2007;16(10): 188697. Kentala 1972 {published data only} Kentala E. Physical tness and feasibility of physical rehabilitation after myocardial infarction in men of working age. Annals of Clinical Research 1972;4(Suppl 9):184. Krachler 1997 {published data only} Krachler M, Lindschinger M, Eber B, Watzinger N, Wallner S. Trace elements in coronary heart disease. Biological Trace Element Research 1997;60(3):17585. Li 2004 {published data only} Li H, Guo L, Sun JZ, Feng JZ, Wang P, Wu GL, et al.Effect of exercise therapy on the quality of life in patients after successful percutaneous transluminal coronary angioplasty. Chinese Journal of Clinical Rehabilitation 2004;8(9):16013. Liao 2003 {published data only} Liao X, Ma H, Dong Y. Effects of early rehabilitation programme on heart rate variability and quality of life in patients with uncomplicated acute myocardial infarction. Journal of Rehabilitation Medicine 2003;18(3):1535. Mezey 2008 {published data only} Mezey B, Kullmann L, Smith K, Sarolta B, Sandori K, Belicza E, et al.Outpatient cardiac rehabilitation: initial experience in the rst Hungarian multicenter study. Orvosi Hetilap 2008;149(8):3539. Peschel 2007 {published data only} Peschel T, Sixt S, Beitz F, Sonnabend M, Muth G, Thiele H, et al.High, but not moderate frequency and duration of exercise training induces downregulation of the expression of inammatory and atherogenic adhesion molecules. European Journal of Cardiovascular Prevention and Rehabilitation 2007;14(3):47682. Piestrzeniewicz 2004 {published data only} Piestrzeniewicz K, Navarro-Kuczborska N, Bolinska H, Jegier A, Maciejewski M. The impact of comprehensive cardiac rehabilitation in young patients after acute myocardial infarction treated with primary coronary intervention on the clinical outcome and leading again a normal life [Korzystne efekty kompleksowej rehabilitacji kardiologicznej u osob do 55 roku zycia, po zawale miesnia sercowego, leczonych za pomoca pierwotnej angioplastyki]. Polskie Archiwum Medycyny Wewnetrznej 2004;111(3): 30917. Roviaro 1984 {published data only} Roviaro S, Holmes DS, Holmsten RD. Inuence of a cardiac rehabilitation program on the cardiovascular,
17
psychological, and social functioning of cardiac patients. Journal of Behavioral Medicine 1984;7(1):6181. Schumacher 2006 {published data only} Schumacher A, Peersen K, Sommervoll L, Seljeot I, Arnesen H, Otterstad JE. Physical performance is associated with markers of vascular inammation in patients with coronary heart disease. European Journal of Cardiovascular Prevention and Rehabilitation 2006;13(3):35662. Stenlund 2005 {published data only} Stenlund T, Lindstrm B, Granlund M, Burell G. Cardiac rehabilitation for the elderly: Qi Gong and group discussions. European Journal of Cardiovascular Prevention and Rehabilitation 2005;12(1):511. Takeyama 2000 {published data only} Takeyama J, Itoh H, Kato M, Koike A, Aoki K, Fu LT, et al.Effects of physical training on the recovery of the autonomic nervous activity during exercise after coronary artery bypass grafting: effects of physical training after CABG. Japanese Circulation Journal 2000;64(11):80913. Tokmakidis 2003 {published data only} Tokmakidis SP, Volaklis KA. Training and detaining effects of a combined-strength and aerobic exercise program on blood lipids in patients with coronary artery disease. Journal of Cardiopulmonary Rehabilitation 2003;23(3):193200. Volaklis KA, Douda HT, Kokkinos PF, Tokmakidis SP. Physiological alterations to detraining following prolonged combined strength and aerobic training in cardiac patients. European Journal of Cardiovascular Prevention and Rehabilitation 2006;13(3):37580. Wosornu 1996 {published data only} Wosornu D, Bedford D, Ballantyne D. A comparison of the effects of strength and aerobic exercise training on exercise capacity and lipids after coronary artery bypass surgery. European Heart Journal 1996;17(6):85463. Zheng 2008 {published data only} Zheng H, Luo M, Shen Y, Ma Y, Kang W. Effects of 6 months exercise training on ventricular remodelling and autonomic tone in patients with acute myocardial infarction and percutaneous coronary intervention. Journal of Rehabilitation Medicine 2008;40(9):7769.
study - rationale, design, and methodological issues. Clinical Trials 2007;4:54859. Pater 2000 {published data only} Pater C, Jacobsen C, Rollag A, Sandvik L, Erikssen J, Kogstad E. Design of a randomized controlled trial of comprehensive rehabilitation in patients with myocardial infarction, stabilized acute coronary syndrome, percutaneous transluminal coronary angioplasty or coronary artery bypass grafting: Akershus Comprehensive Cardiac Rehabilitation Trial (the CORE Study). Current Controlled Trials in Cardiovascular Medicine 2000;1(3):17783.
Additional references
Balady 2007 Balady GJ, Williams MA, Ades PA, Bittner V, Comoss P, Foody JM, et al.Core components of cardiac rehabilitation/ secondary prevention programs: 2007 update: a scientic statement from the American Heart Association Exercise, Cardiac Rehabilitation, and Prevention Committee, the Council on Clinical Cardiology; theCouncils on Cardiovascular Nursing, Epidemiology and Prevention, and Nutrition, Physical Activity, and Metabolism; and the American Association of Cardiovascular and Pulmonary Rehabilitation. Circulation 2007;115:267582. Beswick 2004 Beswick AD, Rees K, Griebsch I, Taylor FC, Burke M, West RR, et al.Provision, uptake and cost of cardiac rehabilitation programmes: improving services to under-represented groups. Health Technology Assessment 2004;8(iii-iv,ix-x): 1152. Bethall 2008 Bethell H, Lewin R, Evans J, Turner S, Allender S, Petersen S. Outpatient cardiac rehabilitation attendance in England: variability by region and clinical characteristics. Journal of Cardiopulmonary Rehabilitation and Prevention 2008;28: 38691. British Heart Foundation 2005 British Heart Foundation. European Cardiovascular Disease Statistics. London: British Heart Foundation, 2005. Brown 2010 Brown JPR, Clark AM, Dalal H, Welch K, Taylor RS. Patient education in the contemporary management of coronary heart disease. Cochrane Database of Systematic Reviews 2010, Issue 12. [DOI: 10.1002/14651858.CD008895] Clark 2005 Clark AM, Hartling L, Vandermeer B, McAlister FA. Metaanalysis: secondary prevention programs for patients with coronary artery disease. Annals of Internal Medicine 2005; 143(9):65972. Clausen 1976 Clausen JP, Trap-Jensen J. Heart rate and arterial blood pressure during exercise in patients with angina pectoris: effects of exercise training and of nitroglycerin. Circulation 1976;53:436-42.
18
References to studies awaiting assessment

Son 2008 {published data only} Son YJ. The development and effects of an integrated symptom management program for prevention of recurrent cardiac events after percutaneous coronary intervention. Journal of Korean Academy of Nursing 2008;38(2):21728.
References to ongoing studies

Blumenthal 2007 {published data only} Blumenthal JA, Sherwood A, Rogers SD, Babyak MA, Doraiswamy PM, Watkins L, et al.Understanding prognostic benets of exercise and antidepressant therapy for person with depression and heart disease: the UPBEAT
Davies 2010a Davies EJ, Moxham T, Rees K, Singh S, Coats AJS, Ebrahim S, et al.Exercise-based rehabilitation for heart failure. Cochrane Database of Systematic Reviews 2010, Issue 4. [DOI: 10.1002/14651858.CD003331] Davies 2010b Davies P, Taylor F, Beswick A, Wise F, Moxham T, Rees K, et al.Promoting patient uptake and adherence in cardiac rehabilitation. Cochrane Database of Systematic Reviews 2010, Issue 7. [DOI: 10.1002/14651858.CD007131.pub2] Egger 1997 Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple graphical test. BMJ 1997;315:62934. Evans 2002 Evans JA, Turner SC, Bethell HJN. Cardiacrehabilitation: are the NSF milestones achievable?. Heart 2002;87(Suppl ii):414. Fletcher 2001 Fletcher GF, Balady GJ, Amsterdam EA, Chaitman B, Eckel R, Fleg J, et al.Exercise standards for testing and training: a statement for healthcare professionals from the American Heart Association. Circulation 2001;104:16941740. Graham 2007 Graham I, Atar D, Borch-Johnsen K, Boysen G, Burell G, Cifkova R, et al.European guidelines on cardiovascular disease prevention in clinical practice: full text. Fourth Joint Task Force of the European Society of Cardiology and other societies on cardiovascular disease prevention in clinical practice (constituted by representatives of nine societies and by invited experts). European Journal of Cardiovascular Prevention and Rehabilitation 2007;14(Suppl 2):1113S. Hambrecht 2000 Hambrecht R, Wolff A, Gielen S, Linke A, Hofer J, Erbs S, et al.Effect of exercise on coronary endothelial function in patients with coronary artery disease. New England Journal of Medicine 2000;342:454-60. Heran 2008a Heran BS, Wong MM, Heran IK, Wright JM. Blood pressure lowering efcacy of angiotensin converting enzyme (ACE) inhibitors for primary hypertension. Cochrane Database of Systematic Reviews 2008, Issue 4. [DOI: 10.1002/14651858.CD003823.pub2] Heran 2008b Heran BS, Wong MMY, Heran IK, Wright JM. Blood pressure lowering efcacy of angiotensin receptor blockers for primary hypertension. Cochrane Database of Systematic Reviews 2008, Issue 4. [DOI: 10.1002/ 14651858.CD003822.pub2] Higgins 2011 Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. Available from www.cochrane-handbook.org.
NICE 2007 National Institute for Health and Clinical Excellence. Secondary prevention in primary and secondary care for patients following a myocardial infarction. NICE 2007. www.nice.org.uk/CG48 (accessed 1 May 2010). OConnor 1989 OConnor GT, Buring JE, Yusuf S, Goldhaber SZ, Olmstaed EM, Paffenbarger RS, et al.An overview of randomized trials of rehabilitation with exercise after myocardial infarction. Circulation 1989;80:23444. Oldridge 1988 Oldridge NB, Guyatt GH, Fischer ME, Rimm AA. Cardiac rehabilitation after myocardial infarction. Combined experience of randomised clinical trials. JAMA 1988;260: 94550. Oldridge 1993 Oldridge N, Furlong W, Feeny D, Torrance G, Guyatt G, Crowe J, et al.Economic evaluation of cardiac rehabilitation soon after acute myocardial infarction. American Journal of Cardiology 1993;72:15461. Oldridge 2003 Oldridge N. Assessing health-related quality of life: it is important when evaluating the effectiveness of cardiac rehabilitation?. Journal of Cardiopulmonary Rehabilitation 2003;23:268. Peterssen 2005 Peterssen S, Peto V, Scarborough PRM. Coronary Heart Statistics. London: British Heart Foundation, 2005. Rees 2004 Rees K, Bennett P, West R, Davey Smith G, Ebrahim S. Psychological interventions for coronary heart disease. Cochrane Database of Systematic Reviews 2004, Issue 2. [DOI: 10.1002/14651858.CD002902.pub2] Taylor 1998 Taylor RS, Kirby BJ, Burdon D, Caves R. The assessment of recovery in post-myocardial infarction patients using three generic quality of life measures. Journal of Cardiopulmonary Rehabilitation 1998;18:13944. Taylor 2006 Taylor RS, Unal B, Critchley JA, Capewell S. Mortality reductions in patients receiving exercise-based cardiac rehabilitation: How much can be attributed to cardiovascular risk factors improvements?. European Journal of Cardiopulmonary Rehabilitation 2006;136:36974. Taylor 2010 Taylor RS, Dalal H, Jolly K, Moxham T, Zawada. A homebased versus centre-based cardiac rehabilitation. Cochrane Database of Systematic Reviews 2010, Issue 1. [DOI: 10.1002/14651858.CD007130.pub2] Unal 2000 Unal B, Critchley J, Capewell S. Explaining the decline in coronary heart disease mortality in England and Wales between 1981 and 2000. Circulation 2000;109:11017.
19
WHO 2004 World Health Organization. Atlas of Heart Disease and Stroke. Geneva: WHO, 2004.
References to other published versions of this review

Jolliffe 2001 Jolliffe J, Rees K, Taylor RRS, Thompson DR, Oldridge N, Ebrahim S. Exercise-based rehabilitation for coronary heart disease. Cochrane Database of Systematic Reviews 2001, Issue 1. [DOI: 10.1002/14651858.CD001800] Taylor 2004 Taylor RS, Brown A, Ebrahim S, Jolliffe J, Noorani H, Rees K, et al.Exercise-based rehabilitation for patients with coronary heart disease: systematic review and metaanalysis of randomized controlled trials. American Journal of Medicine 2004;116(110):68292. Indicates the major publication for the study
20
CHARACTERISTICS OF STUDIES
Characteristics of included studies [ordered by study ID]

Andersen 1981 Methods Post MI randomised four weeks after discharge. 88 participants were randomised, but 13 failed to follow up. Therefore 75 took part in the study 75 men < 66 yrs with 1st MI. Mean age I = 52.2 (+/-7.5), C = 55.6 (+/-6.3). Aerobic activity e.g. running, cycling, skipping + weights for 1 hour x 2 weekly for 2 months, then x 1 week for 10 months. Then continue at home. F/U @ 1, 13, 25, & 37 months post discharge. Total & CHD mortality and non fatal MI. Several participants in C trained on own initiative, but were analysed as intention to treat. Authors concluded that PT after MI appears to reduce consequences and to improve PWC, but PWC declines once participant on their own. PT had no effect on period of convalescence or return to work, but age and previous occupation were of signicance
Participants
Interventions
Outcomes Notes
Risk of bias Bias Authors judgement Support for judgement random numbers
Random sequence generation (selection Low risk bias) Allocation concealment (selection bias) Unclear risk
Not reported. Unclear in terms of assessment of outcomes.
Blinding (performance bias and detection Unclear risk bias) All outcomes Incomplete outcome data (attrition bias) All outcomes Selective reporting (reporting bias) High risk
15% lost to follow-up, no description of withdrawals or dropouts No information reported.
Unclear risk
21
Belardinelli 2001 Methods RCT, single centre in Italy 33 (SD 7) months N Randomised: Total:118 (99 males, 19 females); EX: 59 (49 males, 10 females) UC: 59 (50 males, 9 females) Diagnosis (% of pts); Myocardial Infarction: EX 51; UC 47 Hypercholesterolemia: EX 61; UC 54 Diabetes: EX 17; UC 20 Hypertension: EX 42; UC 47 LVEF (%): EX 52 (SD 16); UC 50 (SD 14) Case mix: Age (years): EX: 53 (SD 11); UC: 59 (SD 10) Percentage male: EX 83.1%; UC 84.8% Percentage white: Not reported Inclusion/exclusion criteria: Inclusion: successful procedure of coronary angioplasty in 1 or 2 native epicardial coronary arteries and ability to exercise Exclusion: previous coronary artery procedures, cardiogenic shock, unsuccessful angioplasty (dened as residual stenosis>30% of initial value), complex ventricular arrhythmias, uncontrolled hypertension and diabetes mellitus, creatinine ?2.5 mg/dl, orthopedic or neurological limitations to exercise or unstable angina after procedure and before enrolment Exercise: Total duration: six months aerobic/resistance/mix: exercise sessions were performed at the hospital gym and were supervised by a cardiologist frequency: 3 sessions/week duration: 15 min of stretching and callisthenics; 5 min of loadless warm-up; 30 min of pedaling on electronically braked cycle ergometer at target work rate; 3 min of unloaded cool-down pedaling intensity: 60% of peak oxygen uptake (VO2 ) modality: electronically braked cycle ergometer Usual care: Control patients were recommended to perform basic daily mild physical activities but to avoid any physical training. Cardiac mortality; myocardial infarction; coronary angioplasty (percutaneous transluminal coronary angioplasty, coronary stent); coronary artery bypass graft; health-related quality of life: MOS Short-Form General Health Survey
Participants
Interventions
Outcomes
Notes Risk of bias Bias Authors judgement Support for judgement
22
Belardinelli 2001
(Continued)
Random sequence generation (selection Unclear risk bias) Allocation concealment (selection bias) Unclear risk
Not reported.
Not reported. All studies were performed by experienced operators and evaluated by two independent observers blinded to treatment arm and to each others interpretation. Comment: This only applied to exercise test & angiography only so assessment of events and health-related quality of life (although patient self complete) not necessarily blinded Cardiac events of 12 patients who were excluded not accounted for No information reported.
Blinding (performance bias and detection Unclear risk bias) All outcomes
Incomplete outcome data (attrition bias) All outcomes Selective reporting (reporting bias)
High risk
Unclear risk
Bell 1998 Methods Post MI Randomised 4-6 days post event. 311 men / 89 women < 65 yrs. Mean ages for women 60.7 (+/- 7.2) to 64.3 (+/-7.3), for men 57.8(+/- 8.9) to 59.4 (+/- 9.4). 2 comparisons conventional CR v: the Heart Manual (HM) and HM v: control Conventional CR - 1 to 2 group classes per week, walking etc other days for 8-12 weeks with multidisciplinary team HM - individual - walking programme up to 6 weeks post MI, facilitator and written text. F/U - 1 year. Total mortality, health-related quality of life: Nottingham Health Prole Heart Manual is a comprehensive home based programme which included an exercise regimen, relaxation and stress management techniques, specic self-help treatments for psychological problems commonly experienced by MI patients and advice on coronary risk-related behaviours. Hospital readmissions signicantly reduced in Heart Manual group compared with conventional CR and control in initial 6 month period
Participants
Interventions
Outcomes Notes
23
Bell 1998
(Continued)
Risk of bias Bias Authors judgement Support for judgement Randomisation was achieved by providing each hospital with a series of sealed envelopes containing cards evenly distributed between conditions. The envelopes were taken sequentially and, before opening the envelope, the patients surname was written diagonally across the sealed ap, in such a way that when the envelope was opened the name was torn in two. Opened envelopes were retained and returned to the trial coordinator. The importance of remaining neutral when advising the patients of the outcome of randomisation was emphasised in the written protocol and was reinforced during the sessions which were held to familiarise facilitators with the protocol. Randomisation was achieved by providing each hospital with a series of sealed envelopes containing cards evenly distributed between conditions. The envelopes were taken sequentially and, before opening the envelope, the patients surname was written diagonally across the sealed ap, in such a way that when the envelope was opened the name was torn in two. Opened envelopes were retained and returned to the trial coordinator. The importance of remaining neutral when advising the patients of the outcome of randomisation was emphasised in the written protocol and was reinforced during the sessions which were held to familiarise facilitators with the protocol. Comment: Patients were informed of outcome of randomisation. Unclear in terms of assessment of outcomes.
Random sequence generation (selection Low risk bias)
Allocation concealment (selection bias)
Low risk
Blinding (performance bias and detection Unclear risk bias) All outcomes Incomplete outcome data (attrition bias) All outcomes Selective reporting (reporting bias) Low risk
1.5% lost to follow up and reported description of withdrawals and/or dropouts No information reported.
Unclear risk
24
Bengtsson 1983 Methods Participants RCT; single centre Sweden; F/U 14 months average N=87 (EX n= 44; CON n=43) Gender: 74 men / 13 women Mean age: EX = 55.3 +/- 6.6, CON = 57.1 +/- 6.6. Diagnosis: following acute MI. Ethnicity: NR Inclusion: <65 years with MI Exclusion: decisions based on cardiologist: severe cardiac failure, PMI-syndrome, aortic regurgitation, cerebral infarct hemiparesis, disease of hip, status post-poliomyelitis, amputation of lower extremity, Diabetes with retinopathy, hyper/hypo thyroidism, hyperparathyroidism, mental illness Exercise intervention: Duration: 3 months; Frequency: 30 min twice weekly. Mode: physical training, interval training of large muscle groups, jogging, callisthenics Cointerventions: counselling, social measures, group and individual. Intensity: graded individually Total mortality, CHD mortality, non-fatal MI up to average 14 months Most emphasis on social/ psychological aspects. 171 patients were randomised and at discharge the cardiologist decided whether the patient was t to take part in the rehab programme - 45 patients were excluded at this point. 7 of intervention group declined to take part, but 6 of these were seen at follow up and included in the analysis because control group probably had a comparable number who would have declined further treatment.
Interventions
Outcomes Notes
Risk of bias Bias Authors judgement Support for judgement allocated at random
Blinding (performance bias and detection Unclear risk bias) All outcomes Incomplete outcome data (attrition bias) All outcomes High risk
Description of withdrawals & dropouts: 29% I, 33% C lost to follow up from 126 who took part. 171 were randomised and then 45 excluded by cardiologist No information reported.
Selective reporting (reporting bias)
Unclear risk
25
Bertie 1992 Methods Participants Randomised on day of discharge after MI; F/U 12-24 months. N = 110 (EX n:57; CON n:53) Gender: NR Mean age: EX = 52.1 +/- 1.3, CON = 52.7 +/- 1.3 Diagnosis: <65 yrs with acute myocardial infarction conrmed by typical symptoms, electrocardiographic changes, and a rise in cardiac creatinine kinase isoenzyme Ethnicity: NR Inclusion: Men and women with acute myocardial infarction and had been admitted to Plymouth coronary care unit Exclusion: uncontrolled heart failure; serious rhythm disturbances which persisted and required treatment at time of discharge; another disabling disease Exercise group: Duration: 4 weeks; Frequenty: 2 x week; Mode: standard pulse-monitored group exercise commonly used in the physiotherapy of cardiac patients, 12 station circuit started 3 weeks post discharge Control: standard hospital care Total mortality, non fatal MI, revascularisation; Assessments at day of discharge, 3rd week after discharge; after rehabilitation (for intervention group); four months after infarct and 12-24 months after infarct)
Interventions
Outcomes
Notes Risk of bias Bias Authors judgement Support for judgement randomised
24% lost to follow-up, no description of withdrawals or dropouts No information reported.
Unclear risk
26
Bethell 1990 Methods Participants Parallel RCT; single centre in Alton, Hampshire N: 200 (EX n=99; CON n101=) Gender: 100% men Age: EX = 54.2 (+/-7.2), CON = 53.2 (+/-7.7). Diagnosis: 5 days post MI. Ethnicity:NR Inclusion: < 65 yrs post MI; history of chest pain typical of MI, progressive ECG changes, rise and fall in aspartate transaminase concentrations with at least one reading above 40 units/ml Exclusion: medical or orthopaedic problems that precluded their taking part in the exercise course; insulin dependent diabetes mellitus; atrial brillation; on investigators personal general practice list Exercise group: Duration: 3 months; Frequency: 3x/week; Mode: 8 stage circuit aerobic & weight training. Intensity: 70-85% predicted HRmax Control group: given a short talk on the sort of exercise that they might safely take unsupervised Total mortality, CHD mortality, non fatal MI (11 year follow up published in 1999. 5 year follow up data from unpublished material used for meta analysis.) 229 patients were randomised; 14 in the intervention group and 15 in control dropped out before the rst exercise test due to death, refusal or other problems. Therefore 200 took part in the study Cardiac mortality of 3% pa, once patients survived to be in the trial. Suggests more severely affected patients were not included. Signicant predictors of cardiac death were pulmonary oedema on admission, complications during admission, one or more previous infarcts, increasing age and low initial tness
Interventions
Outcomes
Notes
Risk of bias Bias Authors judgement Support for judgement random letter sequence
16% lost to follow up, no description of withdrawals or dropouts
27
Bethell 1990
(Continued)
Unclear risk
No information reported.
Bck 2008 Methods Participants Parallel RCT, single centre in Sweden N= 37 randomised (EX n=21; CON n=16) 86.5% male. Age 63.6 years Diagnosis: stable CAD and coronary angiographic changes. Ethnicity: NR Inclusion: coronary artery stenosis documented by angiography or previous coronary artery bypass grafting, classes I-III angina pectoris, classied according to Canadian Cardiovascular Society Exclusion: disabling disease that hindered regular exercise, or if the patient already has engaged in exercise more than 3 days/week Ttraining - high frequency exercise- group: 3 endurance resistance exercises and trained on a bicycle ergometer 30 min, 5 times a week for 8 months at 70% of V02max. Duration: 8 months PTCA at 2 months before PCI and 6 months after PCI
Interventions
Outcomes Notes Risk of bias Bias
Authors judgement
Support for judgement randomised
8.1% lost to follow-up, no description of withdrawals or dropouts No information reported.
Unclear risk
28
Carlsson 1998 Methods Participants RCT; single-centre in Sweden; F/U 1 year N= 235 (EX n=118; CON n=117) Diagnosis: AMI or CABG (4 weeks post discharge); CABG (n = 67); AMI (n = 168) Mean age: AMI patients I = 62.2 +/-5.8, C = 61.7 +/-6, CABG patients Mean age I = 62.7 +/- 4.8, C = 59.8 +/- 4.8. Ethnicity: NR Inclusion:Acute MI; coronary artery bypass revascularization surgery less than 2 weeks prior; PTCA less than 2 weeks prior Exclusion: signs of unstable angina; signs of ST-depression at exercise test of more than 3 mm in 2 chest leads or more than 2mm in two limb leads at four weeks post discharge from hospital, signs of CHF, severe, non-cardiac disease; drinking problems, not Swedish spoken Exercise programme: Duration: 2-3 months; Frequency: 2-3 x weekly Session duration: 60 mins; Mode: walking and jogging followed by relaxation and light stretching exercises; Nurse counselling: 9 hours of counselling in individual & group sessions over 1 year; smoking cessation 1.5, dietary management 5.5 & physical activity 2 hours Control: usual care Mortality, Groups of 20 patients randomly allocated to intervention and control groups (usual care) . Randomised 4 weeks post discharge In rst 3 weeks post discharge all participants ( I & C) had 2 visits by nurse & 1 by cardiologist + all participants invited to join regular exercise group x 1 per week for 30 mins information & 30 mins easy interval training
Interventions
Outcomes Notes
Risk of bias Bias Authors judgement Support for judgement Not reported.
<20% lost to follow up, no description of withdrawals or dropouts

29
Carlsson 1998
(Continued)
Unclear risk
Carson 1982 Methods Participants Randomised 6 weeks post admission N: 303 (EX n=151; CON n=152) 100% men Mean age: EX = 50.3 (SE 0.65) years CON =52.8 (SE 0.67) years Diagnosis: MI Ethnicity: NR Inclusion: MI patients admitted to the coronary care unit; diagnosis based on ECG changes and /or elevation of serum glutamic oxaloacetic transaminase or lactic dehydrogenase taken on three consecutive days ExclusIon: >70 years; heart failure at follow-up clinic; cardio-thoracic ratio exceeding 59%; severe chronic obstructive lung disease; hypertension requiring treatment; diabetes requiring insulin; disabling angina during convalescence; orthopaedic or medical disorders likely to impede progress in the gym, personality disorders likely to render patient unsuitable for the course Exercise group: Duration: 12 weeks; Frequency: attended gym 2 x weekly : Mode: Exercises arranged on a circuit basis and pure isometric exercise was avoided. Control group: Did not attend gym Total mortality, non fatal MI at 5 months, 1 year, 2 year and 3 year after MI (mean F/ U 2.1 years) There appears to be a reduction in mortality in exercise participants with inferior MI
Interventions
Outcomes
Notes Risk of bias Bias
Authors judgement
Support for judgement randomly allocated
21% lost to follow up, no description of withdrawals or dropouts No information reported.
Unclear risk
30
DeBusk 1994 Methods Participants Interventions Randomised 3rd day post MI. 294 men & 8 women F <70 yrs (mean age 57+/- 8), post MI, in 5 centres Nurse managed, home based, multifactorial risk factor intervention programme with exercise training based on De Busk/Miller. F/U 12 months Total mortality Levels of psychological distress dropped signicantly for both groups by 12 months
Authors judgement
33% lost to follow up, no description of withdrawals & dropouts No information reported.
Unclear risk
Dugmore 1999 Methods Participants single-centre RCT in UK; f/u 5 yrs N=124 (EX n=62; CON n=62) Gender: 122 men Mean age: EX=54.8 y ;CON = 55.7 y Diagnosis: clinically documented MI between 1984 and 1988 Ethnicity: NR Inclusion: MI according to conventional WHO cardiac enzyme and ECG criteria of MI Exclusion: NR EX : Duration: 12 months; Frequency: 3 times weekly; Mode: regular aerobic and local muscular endurance training , consisting of warm up and cool down exercises, sit ups, wall bar/bench step ups, cycle ergometry, and major component centered on training of aerobic capacity, using walking and jogging Control: received no formal exercise training throughout the same 12 month period CV mortality; nonfatal MI; QoL at 4, 8, 12 months
31
Interventions
Outcomes
Dugmore 1999
(Continued)
Notes Risk of bias Bias Authors judgement Support for judgement randomly allocated
Not reported. Not reported.
All patients accounted for.
Unclear risk
Engblom 1996 Methods Participants Single-centre open RCT in Finland N Randomised: Total: 228 (201 males, 27 females); EX: 119 (104 males, 15 females) UC: 109 (97 males, 12 females) Baseline Characteristics: Previous unstable angina (%): EX: 29; UC: 31 Previous MI (%): EX: 42; UC: 46 Hypertension (%): EX 31;UC 23 LVEF (%): EX: 70.3 (SD 11.5); UC: 71.4 (SD 12.3) Age (years): EX: 54.1 (SD 5.9); UC: 54.3 (SD 6.2) Percentage male: 88% Percentage white: Not reported Inclusion/exclusion criteria: Inclusion: patients who underwent elective CABS Exclusion: any other serious disease; ?65 years of age 4 stage rehab over 30 months starting pre CABG with meeting of physician, psychologist and OT/PT. 6-8 weeks post CABG - 3 weeks IP with group sessions with psychologist, aerobic physical activity, relaxation & group discussion. 8 months post CABG - 2 days meeting with OT, nutritionist, physician, physio. 30 months post CABG - one day with nutritionist, physician & exercise.
32
Interventions
Engblom 1996
(Continued)
F/U I year & 6 years Usual care: no further details Outcomes Notes Mortality, CABG, health-related quality of life: Nottingham Health Prole 5 years after CABG only 20% of participants were working, despite 90% of patients being in functional classes 1-2. Almost half of patients had retired pre CABG. Many other factors affect RTW post CABG - age, education, physical requirements of the job, type of occupation, self employed status, non work income, personality type, self perception of working capacity and mostly length of absence from work pre CABG
Not reported. open randomised trial Data on deaths & admissions from the hospital records department 13% lost to follow up, no description of withdrawals or dropouts No information reported.
Blinding (performance bias and detection High risk bias) All outcomes Incomplete outcome data (attrition bias) All outcomes Selective reporting (reporting bias) High risk
Unclear risk
Erdman 1986 Methods Participants Single centre RCT in Rotterdam; Follow up 5 years. N= 80 (EX n=; CON n=) Gender: 100% male Mean age: 51years (range 35-60 years) Diagnosis: within 6 months post MI. Also with CABG/angina. Ethnicity: NR Inclusion: First MI within 6 months before the rst psychologic investigation; <65 years; meet three psychologic inclusion criteria - one or more symptoms of the anxiety reaction, diminished self-esteem, positive motivation to take part in the programme Exclusion: severe cardiomyopathy, severe valvular disorders, inadequate performance on exercise, unstable angina pectoris Exercise intervention: duration: 6 months: Frequency: once per week; Session duration and mode: warming up period (15min), gymnastics and jogging (both 15 mins), sports such as volleyball, soccer, and hockey (30min), relaxation exercise (5min) Controls:Usual care plus educational brochure with guidelines about physical tness
33
Interventions
Erdman 1986
(Continued)
training Outcomes Notes Mortality, non fatal MI at 5 years Complex presentation of results. Authors conclude that patients who will benet from rehab can be detected on psychological grounds. Those who have engaged in habitual exercise, but feel seriously disabled, yet do not feel inhibited in a group will benet from rehab
Risk of bias Bias Authors judgement Support for judgement randomly allocated by means of a table for random numbers Not reported. Unclear in terms of assessment of outcomes.
29 % lost to follow up, no description of withdrawals or dropouts No information reported.
Unclear risk
Fletcher 1994 Methods Participants Prospecitve, single centre RCT in the US. F/U 6 months. N= 88 (EX n=41; CON n=47) 100% male Mean age: EX= 62 +/- 8, CON = 63 +/- 7; (range 42 - 72) Diagnosis: CAD and a physical disability Ethnicity: NR Inclusion: 73 years; CAD and physical disability. CAD documented by history of MI, coronary artery bypass surgery, percutaneous transluminal coronary angioplasty or angiographically demonstrated CAD; have the functional use of more than 2 extremities, 1 being an arm, in order to perform the exercise test and training protocols Exclusion: uncontrolled hypertension or diabetes mellitus, clinically signicant cardiac dysrhythmias, unstable angina pectoris, cognitive decits, or other problems that would interfere with compliance to the prescribed exercise and diet protocol Exercise group (Home exercise training programme): Duration: 6 months; Frequency: 5 days/week; Session duration: 20mins/day; Intensity: 85% of predicted maximal heart rate Mode: stationary wheelchair ergometer Control group: routine care
34
Interventions
Fletcher 1994
(Continued)
Total mortality, non fatal MI at 6 months The treatment programme decreased myocardial oxygen demand.
Authors judgement
Support for judgement randomized
Not reported. The same experienced cardiologist interpreted all echocardiograms and was unaware of randomization procedures 32% lost to follow up, no description of withdrawals or dropouts No information reported.
Blinding (performance bias and detection Low risk bias) All outcomes Incomplete outcome data (attrition bias) All outcomes Selective reporting (reporting bias) High risk
Unclear risk
Fridlund 1991 Methods Participants Single centre RCT in Sweden. F/U 1 & 5 years. N=178 (EX n=87; CON n=91) randomized N=116 (EX n=53; CON n=63) participated in the 1year F/U Gender: 101 men & 15 women Mean age: EX=55 years CON=57.6 years Ethnicity: NR Inclusion: 65 years or younger at the time of MI; independent living in the Health Care District after discharge from hospital; meaningful communication and rehabilitation that was not hindered by the MI or other serious illness Exclusion:cerebral or cardiac disorders or serious alcohol abuse Exercise group: Duration: 6months; Frequency: 1 weekly; Session duration: 2hrs; Mode: 1 hours exercise + 1 hours group discussion led by nurse Control: routine cardiac follow-up Total mortality, non fatal MI, revascularisations Positive long term effects on physical condition, life habits, cardiac health knowledge. No effects found for cardiac events or psychological condition
Interventions
Outcomes Notes
Risk of bias
35
Fridlund 1991
(Continued)
Bias
Authors judgement
Support for judgement randomly subdivided
Unclear risk
Giallauria 2008 Methods Participants Parallel single centre RCT in Italy; 6 month F/U N=61 (EX n=30; CON n=31) 72.1% male. Mean age: EX=55.9 years; CON=55.1 years Diagnosis: post-infarction Ethnicity: NR Inclusion: acute ST elevation MI Exclusion: residual myocardial ischemia, severe ventricular arrhythmias, AV block, valvular disease requiring surgery, pericarditis, severe renal dysfunction (creatinine >2.5 mg/ dL) Exercise group: Duration: 6 month; Frequency: 3x/week; Session duration: 30 min; Mode: bicycle ergometer; Intensity: target of 60-70% of Vo2 peak achieved at the initial symptom-limited cardiopulmonary exercise test Control group: discharged with generic instructions to maintaining physical activity and a correct lifestyle Fatal/non-fatal MI (6month F/U)
Interventions
Authors judgement
Random sequence generation (selection Unclear risk bias)
36
Giallauria 2008
(Continued)
Unclear risk
Not reported. The physician performing all Dopplerechocardiography and cardiopulmonary exercise tests was unaware of the results of blood sampling and was blinded to the patient allocation into the study protocol Unclear in terms of assessment of outcomes. All patients were accounted for.
Low risk
Unclear risk
Haskell 1994 Methods Participants Multicentre parallel RCT (4 centres in US) ; F/U 4 years N=300 (EX n=145; CON n=155) Gender: 259 men & 41 women Mean age: EX = 58.3 =/- 9.2, CON = 56.2 +/- 8.2. Diagnosis: CAD Ethnicity: NR Inclusion: < 75 years; clinically indicated coronary arteriography. After arteriography, patients received PTCA or CABG and remained eligible if at least one major coronary artery had a segment with lumen narrowing between 5% and 69% that was unaffected by revascularization procedures Exclusion: severe congestive heart failure, pulmonary disease, intermittent claudication, or noncardiac life-threatening illnesses; no qualifying segments, medical complication occurred during angiography, left ventricular ejection fraction of less than 20%, or patient was in another research study Exercise group (risk reduction group): Intructed by dietitian in a low-fat, low-cholesterol, and high-carbohydrate diet with a goal of <20% of energy intake from fat, <6% from saturated fat, and <75mg of cholesterol per day. Physical activity program : increase in daily activities such as walking, climbing stairs, and household chores and a specic endurance exercise training program with the exercise intensity based on the subjects treadmill exercise test performance. (Nurse managed, home based programme based on Miller, with specic goals to be attained) Control group: usual care F/U 4 years. Total & CHD mortality, non fatal MI, revascularisation at yr 1, 2, 3 and 4 The rate of change in the minimal coronary artery diameter was 47% less in I than C. This was still signicant when adjusted for age and baseline segment diameter (p=0.03)
Interventions
Outcomes Notes
37
Haskell 1994
(Continued)
Risk of bias Bias Authors judgement Support for judgement stratied random numbers in sealed envelopes stratied random numbers in sealed envelopes Unclear in terms of assessment of outcomes.
Random sequence generation (selection Low risk bias) Allocation concealment (selection bias) Low risk
Unclear risk
Heller 1993 Methods Cluster randomised multi-centre study (hospitals in and around Newcatle, Australia); F/U of 6 months N=450 (EX n=213; CON n=237) 71% male Mean age: EX = 59 +/- 8, CON = 58 +/- 8 years Diagnosis: Ethnicity: NR Inclusion: <70 years with a suspected heart attack registered by the Newcastle collaborating centre of the WHO MONICA Project and discharged alive from hospital Exclusion: renal failure or other special dietary requirements and those considered by their physicians to have endstage heart disease Exercise group: 3 packages to participant 1st package: Step 1Facts on fat kit, together with walking programmme information (also (encouragement to walk in the form of a magnetic reminder sticker), and Quit for Life program for smokers. 2nd package: Step 2-3 Facts on fat kit; exercise log. 3rd package: Step 4-5 Facts on fat kit, together with information regarding local Walking for Pleasure groups Control group: usual care Total mortality, health-related quality of life: QLMI Study outcomes assessed at 6 months Low use of preventative services (dietary, anti smoking) by both groups. 10% of patients received rehab - mostly having had CABG.
38
Participants
Interventions
Outcomes
Notes
Heller 1993
(Continued)
Risk of bias Bias Authors judgement Support for judgement Cluster randomisation by GP.
Unclear risk
Hofman-Bang 1999 Methods Participants Single-center, RCT in Sweden; F/U 2 years N=87 (EX n=46; CON=41) Gender 83.9% male Mean age: EX=53 years; CON=53 years Diagnosis: treated with percutaneous transluminal angioplasty Ethnicity: NR Inclusion: at least one signicant coronary stenosis suitable for PTCA and at least one additional clinically insignicant coronary atherosclerotic lesion that could be evaluated by quantitative computerized angiography; <65 years; employed; able to perform a bicycle ergometer test with a minimum capacity of 70 W following the PTCA; absence of other disease of importance for completion of the programme Exercise group: 12 month rehabilitation programme (intense health education and activities promoting behavioural changes - stress management, diet, exercise and smoking habits). Each subject was assigned a daily individual task including self-observation, Type A behavioural drills, relaxation training and exercise. This programme is followed by 11month step-down period, leaving the patients on their own during the second year of follow up Control group: standard care Cardiovascular mortality, MI, CABG, PTCA, health-related quality of life: AP-QLQ recorded during the 2 years F/U
Interventions
Outcomes
Notes Risk of bias

Hofman-Bang 1999
(Continued)
Bias
Authors judgement
Support for judgement randomly assigned
21.8 % lost to follow up, no description of withdrawals or dropouts No information reported.
Unclear risk
Holmbck 1994 Methods Participants Single centre RCT in Sweden; F/U 1 yr N= 69 (EX n=34; CON n=35) Gender: 67 men & 2 women Mean age 55, range 38 - 63 years Diagnosis: Post-MI Inclusion: Acute MI patients under 65 years of age Exclusion: Not stated by patients have been excluded for being incapable of performing strenuous training due to poor left ventricular function or arrhythmias, orthopaedic disorders, other incapacitating somatic diseases or mental disorders Exercise group: Duration: 12 weeks starting 8 weeks post MI.; Frequency: 2x per week; Session duration and mode: at least 45 mins (bicycling 10 mins, callisthenics 10min, jogging 15 min, relaxation 10min); Intensity: 70% to 85% of peak heart rate at the bicycle test for initial session and workload individually adjusted to obtain the desired maximum heart rate if possible Control group: not enrolled in the training programme Total mortality, non-fatal MI & revascularisation. health-related quality of life: Self report questionnaire. Evaluations at 6 weeks and 1 year post MI Authors found no benet from exercise training. Outcomes were related to self-rated levels of physical and psychological well being
Interventions
Outcomes
Notes
Risk of bias Bias Authors judgement Support for judgement
40
Holmbck 1994
(Continued)
Random sequence generation (selection Low risk bias) Allocation concealment (selection bias) Low risk
Randomization was performed according to random numbers in sealed envelopes Randomization was performed according to random numbers in sealed envelopes Unclear in terms of assessment of outcomes.
14.5% lost to follow up, no description of withdrawals or dropouts No information reported.
Unclear risk
Kallio 1979 Methods Participants RCT in 2 Finnish centres; F/U 3 years. N= 375 (EX n=188; CON n=187) Gender: 80.3% male Mean age: EX=54.4 years; CON=54.1 years Diagnosis; acute myocardial infarction. Ethnicity: NR Inclusion: AMI based on WHO criteria Exercise group (Intervention group) consisted of anti-smoking and dietary advice, and discussions on psychosocial problems as well as a physical exercise programme, tailored to the individuals working capacity determined in a bicycle ergometer test Control group: usual care Total mortality; Cardiovascular mortality (F/U 3 years)
Interventions
Authors judgement
41
Kallio 1979
(Continued)
Low risk
1% lost to follow up.
Unclear risk
Kovoor 2006 Methods Participants RCT in Australia (2 centres); F/U 6 months N=142 (EX n=70; CON n=72) Mean age: EX=56.2; CON=55.8 years Male: EX=89% vs CON=86% Diagnosis: had an AMI Ethnicity: NR Inclusion: AMI; <75 years of age; no angina; <2mm ST-segment depression with exercise and if they attained >7-METS workload; left ventricular ejection fraction >40% or no inducible ventricular tachycardia Exercise (conventional treatment group): 5 week rehabilitation program consisted of exercise, education, and counseling sessions that were held 2 to 4 times per week, including work at 6 weeks after AMI Control group (ERNA - early return to normal activities group): work at 2 weeks after AMI without a formal rehab program Total mortality; fatal/non-fatal mortality; CABG; PTCA; HRQL Assessment at 6 weeks and at 6 months
Interventions
Outcomes
Notes Risk of bias Bias Authors judgement Support for judgement randomisation schedules were generated by an independent investigator Comment: no description of randomisation methods. ...opaque sealed envelopes. These envelopes were opened by the nurse coordinator only at randomization of a patient GHPS..analysed in a blinded fashion by an independent nuclear medicine specialist Comment: Unclear in terms of other relevant outcomes.
Low risk
42
Kovoor 2006
(Continued)
High risk
20.4% lost to follow-up, no description of withdrawals or dropouts No information reported.
Unclear risk
La Rovere 2002 Methods Participants Parallel RCT; single-centre f/u 10 yrs N=95 (EX: n=49; CON: n=46) Age: EX: 51 years; CON: 52 years 100% males Diagnosis: surviving rst uncomplicated MI Ethnicity: NR Inclusion: post MI patients admitted at Centro Medico di Montescano in 1984 and 1985 Exclusion: atrial brillation or abnormal sinus node function, insuline-dependent diabetes, exercise-induced myocardial ischemia, and arterial BP > 160/90 EX : Duration: 4-week endurance training; session duration: 30 minutes, 5 times a week; mode: callisthenics and stationary bicycle ergometry. All patients attended sessions, held by cardiologist and psychologist, dealing with secondary prevention of cardiovascular disease and stressing dietary changes and smoking cessation UC: no training Cardiac mortality; nonfatal MI; CABG at 3 to 4 month intervals from the time of entry into the study for the rst 3 years and contacted periodically by telephone thereafter
Interventions
Outcomes
Notes Risk of bias Bias Authors judgement Support for judgement randomized
Unclear risk
43
Leizorovicz 1991 Methods Participants RCT in 4 participating hospitals in France F/U 2 years N=182 (EX n=61; CON n=60) n=60 for counselling group 100% male Mean age: EX = 51, CON = 49 yrs. Diagnosis: MI Ethnicity: NR Inclusion: admitted to participating CCUs with suspected MI; under 65 years old with typical MI, no major irreversible complication or disability Exclusion: contraindication to exercise testing i.e., recent stroke, disability of lower limbs, uncontrolled heart failure, severe rhythm disturbances, SBP> 180 mmHg, severe angina pectoris, or abnormalities triggered by baseline exercise test Exercise group (rehab programme): Duration: 6 week; Frequency 3x/week; Session duration and mode: 25min cycloergometer Intensity: 80% of maximal heart rate. Also included walking, gymnastic and respiratory physiotherapy, relaxation, recommendations on control of cardiovascular risk factors; recommendations to continue regular physical training at the end of the 6 week programme Control: usual care Non fatal MI, angina, surgery, smoking Only 14% of all MI patients admitted to the participating hospitals were randomised to the trial. Exclusion of women and patients >65 accounted for 60% of exclusions
Interventions
Outcomes
Notes
No losses to follow up.
Unclear risk
44
Lewin 1992 Methods Participants Interventions F/U 1 year 126 men & 50 women, mean age 55.8 yrs, post MI. Heart manual: home based facilitated programme with manual and tapes, 3 stage exercise plan - home, walking and life long, graded according to patients ability. Control had placebo facilitators time. F/U 1 year HRQL: HAD; GHQ Study terminated (due to expiry of funding) before all pts reached 6 or 12-month stage. Anxiety scores showed signicant treatment effect @ 6 weeks and 1 year, depression @ 6 weeks. Pre hospital discharge 52% of all pts had HAD scores indicating clinically signicant anxiety or depression (8+). C were signicantly more anxious and depressed at all follow ups
Outcomes Notes
Risk of bias Bias Authors judgement Support for judgement allocated to the experimental or control group by use of a written pre-determined randomisation protocol Methods not described. Not described. The medical secretary who held the list was blind to the purpose of the study and to the patients taking part, and the cardiologist and nursing staff were blind to which study group the patients were in Unclear in terms of assessment of outcomes. 17% lost to follow up, no description of withdrawals or dropouts
Unclear risk
High risk
Unclear risk
Manchanda 2000 Methods Participants Single-centre RCT in India; f/u 1 yr N=42 (EX n=21; CON n=21) 100% male Mean age: EX = 51 years; CON=52 years Diagnosis: chronic stable angina and angiographically proven CAD Ethnicity: NR Inclusion: chronic stable angina and angiographically proven CAD
45
Manchanda 2000
(Continued)
Exclusion: recent (within last six months) MI or unstable angina Interventions Exercise group: program consisting of yoga at home for average of 90 min daily, control of risk factors, diet control and moderate aerobic exercise Control: usual care = managed by conventional methods i.e. risk factor control and American Heart Association step I diet total mortality; CABG; PTCA Assessments are baseline and 1 yr.
Outcomes
Notes Risk of bias Bias Authors judgement Support for judgement randomized
Not reported. Two independent observers who were blinded to group allocation analysed all arteriograms Blinding of other outcome assessments were not mentioned. All patients accounted for.
Low risk
Unclear risk
Marchionni 2003 Methods Participants Single-centre RCT in Italy; f/u 14 mos N= 270 (EX n=90; Home n=90; CON n=90) Gender: 67.8% males Mean age: 69 years Diagnosis: post-MI Ethnicity: NR Inclusion: >56 years; referred to unit for functional evaluation 4 to 6 weeks after MI Exclusion: severe cognitive impairment or physical disability, left ventricular EF <35%, contraindications to vigorous physical exercise, eligibility for myocardial revascularization because of low-effort myocardial ischemia, refusal, or living too far from the unit
46
Marchionni 2003
(Continued)
Interventions
EX: Hospital-CR: program consisted of 40 exercise sessions: 24 sessions (3/wk) of endurance training on cycle ergometer (5-min warm-up, 20-min training at constant workload, 5-min cool down, 5-min post-exercise monitoring) plus 16 (2/wk) 1-hr sessions of stretching and exibility exercises Home-CR: 4-8 supervised instruction sessions in CR unit, where taught how to perform training at home; then patients received exercise prescription similar to Hosp-CR group CON: no CR, attended single structured session on CV risk factor management with no exercise prescription and were referred back to their family physicians mortality, MI, CABG, PTCA, HRQL at month 2, 8 and 14 costs over study duration
Outcomes
Notes Risk of bias Bias Authors judgement Support for judgement Not reported.
38 (14.1%) dropped out; clinical event data for these patients not reported per treatment group No information reported.
Unclear risk
Miller 1984 Methods Participants Randomised 3 weeks post MI 198 men < 70 yrs with MI. Mean age 52 +/-9. Patients divided into 5 interventions; 1a-extended home 1b-brief home 2a-extended group 2b-brief group 3-ETT but no further training 4-no ETT or training.
47
Interventions
Miller 1984
(Continued)
Home; detailed instructions + HR monitors. If free of ETT induced angina @3 weeks pts used stationary bikes for 30 mins/day, 5 days/week. If had ETT induced angina @ 3 weeks, brisk walking programme for 100 mins/week. 2x weekly telemetry to base from HR monitors. Brief intervention trained for 8 weeks, extended intervention for 23 weeks. Group intervention trained in a group with clinical supervision for 8 or 23 weeks for 3 x 1 hour /week with 100 mins/week at training rate All pts in 1a & b, 2 a & b and 3 received counselling from a physician (30-45 mins ) and nurse (30-45 mins). F/U 23 weeks. Outcomes Notes CHD mortality, non fatal MI and revascularisation Low rate of cardiac events reects identication of low risk population. Group 3 were unexpectedly active, th authors concluding that ETT + good explanation may enhance physical activity in the early stages
Unclear risk
Oldridge 1991 Methods Stratied by status (work type and employed or not) and randomised at time of MI. All participants were depressed and/or anxious (Beck Depression Inventory <5, < 43 on Spielberger State Anxiety Inventory, or <42 on Spielberger Trait Anxiety Inventory.) 177 men & 24 women with MI. Mean age I =52.9+/- 9.5 yrs, C = 52.7 +/- 9.5 yrs. ET for participant & spouse. 50 minutes 2 x weekly for 8 weeks at 65% of HRmax during ETT. Plus cognitive behavioural group intervention of 8 sessions of 1.5 hours + relaxation.
48
Participants
Interventions
Oldridge 1991
(Continued)
CPR training offered to spouse. F/U 1 year. Outcomes Mortality health-related quality of life: QOLMI time trade-off. Both groups improved over 12 months, with the biggest changes occurring in the rst 8 weeks
Notes
Risk of bias Bias Authors judgement Support for judgement randomized
For the primary outcome -HRQL- 9% lost to follow up, no description of withdrawals or dropouts No information reported.
Unclear risk
Ornish 1990 Methods Participants Prospective RCT in US (patients recruited from 2 sites) F/U 5 years N= 48 (EX n=28; CON n=20) Gender: NR for all 48 patients Mean age: EX = 56.1 +/- 7.5; CON=59.8 +/- 9.1 years Diagnosis: moderate to severe CAD (MI, PTCA, CABG, angina) Ethnicity: NR Inclusion: 35-75 years, male or female; residence in the greater San Francisco area; no other life-threatening illnesses; no MI during the preceding 6 weeks, no history of receiving streptokinase or alteplase; not currently receiving lipid-lowering drugs; 1, 2, 3 vessel coronary artery disease (dened as any measurable coronary atherosclerosis in a non-dilated or non-bypass grafting; permission granted by patients cardiologist and primary care physician Exercise intervention: exercise (typically walking) for a minimum of 3 hours per week and 30 min per session; target training heart rate of 50-80%. Co-interventions: stress management, low fat vegetarian diet, group psychosocial support . 1 year duration Control group: usual care.
49
Interventions
Ornish 1990
(Continued)
Outcomes
CHD mortality, non-fatal MI, revascularisation, Assessment at baseline and after 1 year and 5 year I had 91% reduction in reported frequency of angina after 1 year and 72% after 5, C had 186% increase in reported frequency of angina after 1 year and 36% decrease after 5. I had 7.9% relative improvement in coronary artery diameter at 5 years, C had 27.7% relative worsening at 5 years
Notes
Risk of bias Bias Authors judgement Support for judgement randomly assigned
Not reported. ...investigators carrying out all medical tests remained unaware of both patient group assignment and the order of the tests. Different people provided the lifestyle intervention, carried out the tests, analysed the results, and carried out statistical analyses. Coronary arteriograms were analysed without knowledge of sequence or of group assignment. 45/93 (48%) of randomised patients did not participate, no description of withdrawals or dropouts No information reported.
Blinding (performance bias and detection Low risk bias) All outcomes
Incomplete outcome data (attrition bias) All outcomes
High risk
Unclear risk
Schuler 1992 Methods Participants randomised after routine angiography for angina. 66% study population had previous MI. All participants spent one week as inpatient on a metabolic ward receiving instruction on exercise and diet 113 men with CAD, aged 35 - 68 yrs (mean 53.5) 2 further weeks as IP, then daily exercise at home on cycle (30 mins at 75% HR max) + 2 group training sessions of 60 mins/week. Informative session held 5 times/year for participants and spouses. F/U yearly for 6 years.
50
Participants Interventions
Schuler 1992
(Continued)
Outcomes Notes
Total and CHD mortality, non fatal MI, revascularisation, Exercise adherence in the rst year was 68% (39-92%, over the next 5 years 33% (389%). Pts with regression of coronary atheroma attended exercise sessions signicantly more often (54+/- 24%) than patients with no change (20+/- 24%) or progression 31+/- 20%)
Random sequence generation (selection Unclear risk bias) Allocation concealment (selection bias) Low risk
sealed envelopes Unclear in terms of assessment of outcomes.
Unclear risk
Seki 2003 Methods Participants Single centre RCT in Japan; F/U 6 months. N= 38 (EX n=20; CON n=18) 100% male Mean age: 70 years Ethnicity: Japanese patients Diagnosis: Chronic CAD Inclusion: referred at least 6 months after a major coronary event, including acute MI, coronary artery bypass grafting or percutaneous balloon angioplasty for acute coronary syndrome Exercise: Duration 6 months; Frequency: weekly; Session duration and mode: 20-30min upright aerobic and dynamic exercise (walking, bicycling, jogging etc) and light isometric exercise (hand weights) and 20 min cool-down stretching and callisthenics. Intensity: prescribed individually at the anaerobic threshold level at baseline. Patients also encouraged to exercise twice a week outside the clinicCo intervention: dietary and educational program Control group: standard care health-related quality of life at 6 months
51
Interventions
Outcomes
Seki 2003
(Continued)
Notes Risk of bias Bias Authors judgement Support for judgement randomly assigned..by envelope method
randomly assigned..by envelope method Unclear in terms of assessment of outcomes.
All 38 patients accounted for.
Unclear risk
Seki 2008 Methods Participants Single centre RCT in Japan; F/U months N= 39 (EX n=20; CON n=19) 100% male Mean age: 69.5 years Diagnosis: stable CAD Ethnicity: Japanese patients Inclusion: <65 years old with stable CAD Exclusion:ongoing congestive heart failure, liver dysfunction, renal dysfunction, or systemic diseases, including malignancy and collagen disease EX:exercise training Duration 6 months; Frequency: weekly; Session duration and mode: 20-60min upright aerobic and dynamic exercise (walking, bicycling, jogging etc) and light isometric exercise (hand weights) and 15 min cool-down stretching and callisthenics. Intensity: prescribed individually at the anaerobic threshold level as measured by a treadmill exercise test. Patients also encouraged to perform aerobic exercise twice weekly (30 min) at home. Co-intervention: diet therapy, and weekly counselling Control: usual outpatient care Total mortality; non-fatal/fatal mortality. See notes below. No subject in either group showed any worsening of symptoms or had clinical events during this study.
Interventions
Outcomes Notes
Risk of bias
Seki 2008
(Continued)
Bias
Authors judgement
Support for judgement randomly assigned
Blinding (performance bias and detection Unclear risk bias) All outcomes Incomplete outcome data (attrition bias) All outcomes Selective reporting (reporting bias) Unclear risk
Unclear risk
Shaw 1981 Methods Participants treated at one of 5 participating centres. Participants randomised after participating in low level exercise course for 6 weeks 651 men aged 30 - 64 yrs with MI between 8 weeks and 3 years prior to start of study (mean 14 months). Mean age I = 51.5+/- 7.4, C = 52.1 +/- 7.2 ET- 1 hour/day, 3 days/week for 8 weeks. 6 station circuit + gym exercises or swimming and games. F/U 3 years. Long term follow up to 19 years published in 1999, but not used for meta analysis Total & CHD mortality, non fatal MI 90% of ET attended 90% of 24 scheduled sessions post randomisation, only 48% attending > 50% of sessions at 18 months. 30% of control alleged exercising regularly, on own initiative. At 19 years any protective effect form the programme had decreased over time, but an increase with PWC from the beginning to the end of the trial was associates with a consistent reduction in mortality throughout the 19 years of follow up
Participants
Interventions
Outcomes Notes
Risk of bias Bias Authors judgement Support for judgement
53
Shaw 1981
(Continued)
randomized
Unclear risk
Sivarajan 1982 Methods Multicentre study. Random allocation of individuals to two intervention groups (exercise only or exercise plus teaching and counselling) and a control group (usual care) 258 patients (>80% men) aged <71 yrs. Mean age I = 55.6+/- 9.3, 56.3 +/- 8.3, C = 57.1 +/- 7.3. Following acute MI. All patients exercise whilst in hospital. Ex only: Weekly clinic appointments 3 months post discharge for progressive callisthenics and walking. Exercise 2 x daily until RTW and then x 1 daily. Ex + T&C: Same exercise programme + 8 x 1 hour teaching/ counselling sessions with family & friends F/U 6 months. Total mortality; health-related quality of life: Sickness Impact Prole Several reports of the same trial all with various bits of information. Authors conclude that multiple intervention trial of this short duration did not change patients behaviour. MI itself acts as a strong stimulus to alter behaviour with respect to risk factors
Participants
Interventions
Outcomes Notes
Not reported.
54
Sivarajan 1982
(Continued)
Unclear in terms of assessment of outcomes.
Unclear risk
Specchia 1996 Methods Randomised at hospital discharge. All participants went to a rehab centre for 3 weeks for ETT, 24 hour tape. All participants had sessions with cardiologist & psychologist for secondary prevention advice 182 men & 18 women < 65 yrs with MI. Mean age I = 51.5 +/- 7, C = 54.3 +/- 8. 4 weeks supervised cycling for 30 mins 5 days/week + callisthenics @ 75% max work capacity. After discharge to walk for 30 minutes every 2 days. F/U 34 months. CHD mortality, revascularisations Ejection fraction was the only prognostic factor. Among 51 patients with EF <41%, relative risk for the 27 untrained participants was 8. 63 times higher than for 24 trained ones. (p=0.04) If EF > 40%, estimated risk for untrained participant was 1.07 times higher than for trained
Participants
Interventions
Outcomes Notes
Blinding (performance bias and detection Unclear risk bias) All outcomes Incomplete outcome data (attrition bias) All outcomes Low risk
55
Specchia 1996
(Continued)
Unclear risk
Stern 1983 Methods Randomized by blocks of 6 into one of three groups: exercise, group counselling & control. Eligibility - work capacity <7 METs (men), <6 METs (women), Taylor Manifest Anxiety Scale raw score of 19+ and/or Zung self rating Depression Scale raw score of 40+ 91 men & 15 women aged 30-60 yrs with MI between 6 weeks and 1 year prior to entry to study 3 x 1 hour sessions/week over 12 week period for 36 sessions. All exercises dynamic against resistance, exercising upper limb and lower limb alternately for 4 minutes with 2 mins rest in between. Target HR 85% of HRmax at ETT. F/U 1 year. Mortality, non fatal MII Minimal differences between groups at one year.
Participants
Interventions
Authors judgement
Support for judgement Not reported.
Unclear risk
Sthle 1999 Methods Participants Single-centre RCT in Sweden; f/u 1 y 109 patients ?65 years (80% males) admitted to hospital because of acute coronary event (dened as either acute MI, n=64; or episode of unstable angina, n=45) EX: n=56 (mean age = 71 y, range 64-84; 41 men) UC : n=53 (mean age = 68 y, 65-83; 40 men)
56
Sthle 1999
(Continued)
Interventions
EX : 50 min aerobic outpatient group-training programme (including warm-up and cool-down) 3 times a week for 3 mos. Complete programme was supervised by specialized physiotherapist and supported by music which guided intensity of performance during session). Training followed by 10 min of music-supported relaxation. After 3 mos, patients had possibility of participating in programme once a week for another 3 mos UC: encouraged to re-start usual/prior physical activity as soon as they felt t total mortality, CABG, PTCA, health-related quality of life; Karolinska Questionnaire at 12-months
Outcomes
Notes Risk of bias Bias Authors judgement Support for judgement Not reported.
Clinical event data for 8 (7%) who withdrew before 3 months were not accounted for at 1 yr No information reported.
Unclear risk
Toobert 2000 Methods Participants Randomised controlled trial with follow-up of 24 months. 28 postmenopausal women with coronary heart disease, dened as atherosclerosis, MI, percutaneous transluminal coronary angioplasty, and/or coronary bypass graft surgery. Mean age: 64 years Randomised to PrimeTime program (very low-fat vegetarian diet, stress-management training, exercise, group support, and smoking cessation) or to usual care n=17 for PrimeTime program and n=11 for usual care health-related quality of life: SF-36 at 24 months
Interventions
Outcomes Notes
57
Toobert 2000
(Continued)
Not reported Unclear in terms of assessment of outcomes.
3/28 (10.7%) patients lost to follow-up, no description of withdrawals or dropouts No information reported.
Unclear risk
Vecchio 1981 Methods Participants Interventions Randomised after ETT, 30 days after MI. 50 patients aged 40 to 60 yrs with MI (mean 50.1). 6 weeks physical training programme. F/U 1 year. CV mortality Trained patients showed a better mid term prognosis than controls, but this could not be explained by the physical training procedure
Outcomes Notes
24% lost to follow up, no description of withdrawals or dropouts

58
Vecchio 1981
(Continued)
Unclear risk
Vermeulen 1983 Methods Participants Randomised 4-6 weeks post MI after ETT. 98 men aged 40- 55 yrs with MI. Mean age I = 49.4 +/- 3.7, C = 49.1 +/- 4.5. Rehabilitation programme. F/U 5 years Mortality, non fatal MI, Authors conclude that cardiac rehab benets patients after MI due to direct effect on myocardial perfusion and to lowering of cholesterol levels
Interventions
Outcomes Notes
Unclear risk
VHSG 2003 Methods Participants RCT of 2 years duration 197 patients admitted to hospital for acute MI, unstable angina pectoris or after coronary artery bypass grafting. 82.2% male. Mean age: 55 years n=98 for intervention group and n=99 for usual care group. EX: lifestyles intervention program (low fat diet, regular exercise, smoking cessation, psychosocial support and education, delivered by nurses on the rationale for pharmacological and lifestyle measures)
59
Interventions
VHSG 2003
(Continued)
Usual care Outcomes Notes Risk of bias Bias Authors judgement Support for judgement randomised Total mortality
Random sequence generation (selection Unclear risk bias) Allocation concealment (selection bias) Low risk
[Randomization] was performed with pre-prepared sealed opaque envelopes containing details on group allocation. The patients opened the envelopes themselves so that their allocation to IP or UC was revealed to them without the prior knowledge of the study investigators Unclear in terms of assessment of outcomes.
17.8 % lost to follow up, no description of withdrawals or dropouts No information reported.
Unclear risk
WHO 1983 Methods 24 centre, pan European study conducted between 1973 and 1978. Randomised on discharge from hospital. 12 centres accepted for meta analysis 160 Men < 65 yrs with rst or consecutive MI. Mean age for all participants I = 52.3, C = 53.5. Comprehensive programme dependent on local provision. Physical training was not compulsory but was strongly recommended. F/U 3 years Local training for 6 weeks Total mortality, CVD, CHD & sudden death. Fatal & non fatal re-infarction. Methodological problems with the execution of the study allowed only death and reinfarction to be successfully used as endpoints
Participants
Interventions
Outcomes
Notes
60
WHO 1983
(Continued)
Risk of bias Bias Authors judgement Support for judgement Individually randomised, but method unclear. Not reported. Unclear in terms of assessment of outcomes.
No description of withdrawals or dropouts. Varied greatly from site to site No information reported.
Unclear risk
Wilhelmsen 1975 Methods Randomised on discharge. All patients received information on increasing physical activity during convalescence 280 men & 35 women < 55 yrs with MI. Mean age 50.6. Training programme 3 months after MI, 3 x half hour sessions per week based in hospital, at home or in workplace. F/U 5 years Mortality, re-infarction. 1 year post MI, 39% of those who started training were training at the hospital. A further 21% trained at home or at work
Participants
Interventions
Outcomes Notes
Risk of bias Bias Authors judgement Support for judgement By the use of a random number table the patients were allocated... Not reported. The exercise test 1 yr after the MI followed the same protocol but was conducted by another physician, who did not know if the
61
Wilhelmsen 1975
(Continued)
patients belonged to the experimental or the control group. Incomplete outcome data (attrition bias) All outcomes Selective reporting (reporting bias) Low risk No losses to follow up for clinical events.
Unclear risk
Yu 2003 Methods Participants Unblinded, single-centre RCT in China; f/u 2 y 112 obese patients with CHD who had either recent AMI (n=72) or had undergone elective PCI (n=40) within 6 wks EX: n=72 (mean age = 62.3 y; 59 men, 13 women) UC : n=40 (mean age = 61.2 y; 30 men, 10 women) EX : Phase 1 was impatient ambulatory program that lasted 7-14 d; phase 2 was 16session, twice weekly, outpatient exercise and education program lasting for 8 weeks, each session included 1 hr of education class followed by 2 hrs of exercise training, 1st hour of training was conducted by physiotherapist; phase 3 was community-based home exercise program for another 6 mos; phase 4 was long-term follow-up program until end of 2 years which stressed importance of regular exercise and risk factor modication UC: attended 2-hr talk that explained CHD, importance of risk factor modication, and potential benets of physical activity, but without undergoing outpatient exercise training program health-related quality of life: 3F-36 at 8 & 24 months
Interventions
Authors judgement
Support for judgement Not reported.
Not reported. Unclear in terms of assessment of other outcomes.
Unclear risk
62
Yu 2004 Methods Participants Single-center, unblinded, single-centre RCT in China; f/u 2 y 269 patients (76% men; mean age 64 y) with recent AMI (n=193) or after elective percutaneous coronary intervention (n=76) EX: n=181 (mean age, 64 SD 11 y; 138 males, 43 females) UC: n=88 (mean age, 64 SD 11 y; 66 males, 22 females) EX : Phase 1 was impatient ambulatory program that lasted 7-14 d; phase 2 was 16session, twice weekly, outpatient exercise and education program lasting for 8 weeks, each session included 1 hr of education class followed by 2 hrs of exercise training, 1st hour of training was conducted by physiotherapist; phase 3 was community-based home exercise program for another 6 mos; phase 4 was long-term follow-up program until end of 2 years which stressed importance of regular exercise and risk factor modication UC: attended 2-hr talk that explained CHD, importance of risk factor modication, and potential benets of physical activity, but without undergoing outpatient exercise training program Total mortality
Interventions
Authors judgement
Not reported. The QOL assessments were performed on all patients in all 4 phases by a trained social worker who was unaware of the randomization Unclear in terms of assessment of other outcomes. 24 % lost to follow up, no description of withdrawals or dropouts No information reported.
High risk
Unclear risk
63
Zwisler 2008 Methods Participants Pragmatic, open-label, single-centre RCT in Denmark; f/u 1 y 446 patients having IHD (MI or angina pectoris in accordance with European guidelines) EX: n=227 (mean age 67 y) UC: n=219 (mean age 67 y) EX : 6-week intensive rehabilitation program including patient education, 12 exercise training sessions, dietary counseling, smoking cessation, psychosocial support, risk factor management and clinical assessment UC: attended 2-hr talk that explained CHD, importance of risk factor modication, and potential benets of physical activity, but without undergoing outpatient exercise training program Total mortality, MI, CABG, PTCA, health-related quality of life: SF-36 at 1-yr follow up
Interventions
Outcomes
Notes Risk of bias Bias Authors judgement Support for judgement The Copenhagen Trial Unit computer generated the allocation sequence and provided central secretary-staffed telephone randomization The essential patient data were registered, and the result of the randomization as delivered to the research nurse, who informed the CCR team and the patient about the allocation The interventions were open to the patients and investigators. Investigator-independent outcome data from registries were chosen to ensure blinded outcome assessment. The scientic team and CCR team collected secondary outcome measures blinded to intervention at baseline and without blinding at 12 months All IHD patients accounted for.
Random sequence generation (selection Low risk bias)
Low risk
Low risk
Unclear risk
EX: exercise based cardiac rehabilitation

UC: usual care MI: Myocardial infarction CHD: Coronary heart disease SBP: Systolic blood pressure DBP: Diastolic blood pressure HDL: High density lipoprotein LDL: Low density lipoprotein QoL: Quality of life V02max: Maximum oxygen uptake CV: Cardiovascular PWC: physical work capacity. ET: exercise training RTW: return to work
Characteristics of excluded studies [ordered by study ID]
Study Agren 1989 Aronov 2006 Ballantyne 1982 Belardinelli 2007
Reason for exclusion Improper method of randomisation (based on date of birth). No useful outcome data reported. No useful outcome data reported. Abstract only with incomplete reporting of study characteristics and outcome data. Full trial report not published Only a small subset of randomised patients responded via questionnaire. Incomplete outcome data Not a randomised study. Participants divided alternately after admission Control group was not randomised, but selected on geographical basis Method of randomisation was inadequate; of a study population of 265 across 5 centres only one centre randomised their patients, leaving a control group of 50 and an intervention group of 215 No useful outcome data reported. No useful outcome data reported. Duration of follow-up not reported All patients (treatment and control) participated in 3-6 week cardiac rehabilitation programme (including supervised exercise sessions) prior to randomization. Control group was not usual care No useful outcome data reported. No useful outcome data reported.
Bettencourt 2005 Bjrntorp 1972 Blumenthal 1997 Br 1992
Carlsson 1997 Gao 2007 Giannuzzi 2008
Gielen 2003 Heldal 2000
65
(Continued)
Higgins 2001 Jiang 2007 Kentala 1972
No useful outcome data reported. No useful outcome data reported. Quote: On admission the patients were divided up according to their year of birth into a control group and a training group... Not a randomised study. No useful outcome data reported. Follow-up <6 months. Follow-up too short (3-4 weeks) and no useful outcome data reported Not a randomised study. No useful outcome data reported. No useful outcome data reported. Not a randomised study. Assigned to treatment group according to geographic location No useful outcome data reported. No useful outcome data reported. No useful outcome data reported. No useful outcome data reported. No useful outcome data reported. No useful outcome data reported.
Krachler 1997 Li 2004 Liao 2003 Mezey 2008 Peschel 2007 Piestrzeniewicz 2004 Roviaro 1984 Schumacher 2006 Stenlund 2005 Takeyama 2000 Tokmakidis 2003 Wosornu 1996 Zheng 2008
Characteristics of studies awaiting assessment [ordered by study ID]

Son 2008 Methods Participants Interventions Unclear if randomized study. Subjects consisted of 58 CAD patients who underwent PCI (experimental group: 30, control group: 28) The experimental group participated in an integrated symptom management program for 6 months which was composed of tailored education, stress management, exercise, diet, deep breathing, music therapy, periodical telephone monitoring and a daily log The control group received usual care.
66
Son 2008
(Continued)
Outcomes Notes
Recurrent cardiac events, self care activity, quality of life Article in Korean. Unable to nd translator to answer following questions to determine study inclusion: Was this study randomized? How do the authors dene recurrent cardiac events? Any other pre-specied outcomes measured reported? What scale did the authors use to assess self care activity and quality of life
Characteristics of ongoing studies [ordered by study ID]

Blumenthal 2007 Trial name or title The Understanding Prognostic Benets of Exercise and Antidepressant Therapy for Persons with Depression and Heart Disease (UPBEAT) Study 5-year, single-site randomised clinical trial sponsored by the National Heart, Lung, and Blood Institute 200 clinically depressed patients (with scores of Beck Depression Inventory 9) with stable CHD, including a previous (>60 days) myocardial infarction, revascularisation procedure, such as a PTCA or CABG, or a cardiac catheterization demonstrating signicant coronary artery stenosis 4 months of treatment with supervised aerobic exercise, sertraline, or placebo Depressive symptoms, heart rate variability, baroreex control, vascular function (i.e., ow-mediated dilation) , measures of inammation and platelet aggregation Not reported. Blume003@mc.duke.edu This study is not powered to assess treatment group differences in CHD morbidity and mortality.
Methods Participants
Interventions Outcomes
Starting date Contact information Notes
Pater 2000 Trial name or title Methods Akershus Comprehensive Cardiac Rehabilitation Trial (the CORE Study) Randomized, controlled, parallel-group design, single centre trial, driven by the Medical Department of the Akershus Central Hospital in Oslo, Norway 500 patients, men and women, aged 40-85 years, who have sustained at least one of the following: myocardial infarction, acute coronary syndrome, percutaneous transluminal coronary angioplasty and coronary artery bypass grafting
Participants
67
Pater 2000
(Continued)
Interventions
Intervention: 8 weeks of supervised, structured physical training of three periods of 20 min per week, targeting a heart rate of 60-70% of the individuals maximum; home-based physical exercise training with the same basic schedule as in the supervised period; quantication of patients compliance with the exercise programme by the use of wristwatches, information stored in the watch memory being retrieved once a month during the 3-year follow-up period; and life-style modication with an emphasis on the cessation of smoking and on healthy nutrition and weight control Control: Conventional care. Primary: Quality of life. Secondary: total mortality, cardiovascular mortality, morbidity and recurrence rates of coronary events throughout a 3-year follow-up period Originally states as April 2000 with follow up complete by April 2004. No sign of publication to date. Contacted author with no reply drcornelpater@aol.com Study design described at http://cvm.controlled-trials.com/content/1/3/177
Outcomes
Starting date
Contact information Notes
68
DATA AND ANALYSES
Comparison 1. Exercise-based rehabilitation versus usual care
Outcome or subgroup title 1 Total mortality 1.1 Follow-up of 6 to 12 months 1.2 Follow-up longer than 12 months 2 Cardiovascular mortality 2.1 Follow-up of 6 to 12 months 2.2 Follow-up longer than 12 months 3 Fatal and/or nonfatal MI 3.1 Follow-up of 6 to 12 months 3.2 Follow-up longer than 12 months 4 CABG 4.1 Follow-up of 6 to 12 months 4.2 Follow-up longer than 12 months 5 PTCA 5.1 Follow-up of 6 to 12 months 5.2 Follow-up longer than 12 months 6 Hospital Admissions 6.1 Follow-up of 6 to 12 months 6.2 Follow-up longer than 12 months
No. of studies 33 19 16 19 9 12 26 12 16 21 14 9 11 7 6 10 4 7
No. of participants
Statistical method Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI)
Effect size Subtotals only 0.82 [0.67, 1.01] 0.87 [0.75, 0.99] Subtotals only 0.93 [0.71, 1.21] 0.74 [0.63, 0.87] Subtotals only 0.92 [0.70, 1.22] 0.97 [0.82, 1.15] Subtotals only 0.91 [0.67, 1.24] 0.93 [0.68, 1.27] Subtotals only 1.02 [0.69, 1.50] 0.89 [0.66, 1.19] Subtotals only 0.69 [0.51, 0.93] 0.98 [0.87, 1.11]
6000 5790
4130 4757
4216 5682
2312 2189
1328 1322
463 2009
69
Analysis 1.1. Comparison 1 Exercise-based rehabilitation versus usual care, Outcome 1 Total mortality.
Review: Exercise-based cardiac rehabilitation for coronary heart disease
Comparison: 1 Exercise-based rehabilitation versus usual care Outcome: 1 Total mortality
Study or subgroup
Exercise n/N
Usual Care n/N
Risk Ratio M-H,Fixed,95% CI
1 Follow-up of 6 to 12 months Bell 1998 Bertie 1992 Bethell 1990 Carlsson 1998 DeBusk 1994 Engblom 1996 Fletcher 1994 Fridlund 1991 Heller 1993 Holmbck 1994 Kovoor 2006 Manchanda 2000 Oldridge 1991 Schuler 1992 Seki 2008 Sivarajan 1982 Stern 1983 WHO 1983 Wilhelmsen 1975 19/251 0/57 16/113 2/113 12/293 12/119 3/41 9/87 6/213 1/34 0/72 0/21 3/99 2/56 0/20 6/174 0/42 60/1208 19/158 8/102 3/53 12/116 2/112 10/292 13/109 4/47 14/91 3/237 1/35 0/70 0/21 4/102 1/57 0/19 2/84 1/29 76/1096 29/157 0.97 [ 0.44, 2.13 ] 0.13 [ 0.01, 2.52 ] 1.37 [ 0.68, 2.76 ] 0.99 [ 0.14, 6.91 ] 1.20 [ 0.52, 2.72 ] 0.85 [ 0.40, 1.77 ] 0.86 [ 0.20, 3.62 ] 0.67 [ 0.31, 1.47 ] 2.23 [ 0.56, 8.79 ] 1.03 [ 0.07, 15.80 ] 0.0 [ 0.0, 0.0 ] 0.0 [ 0.0, 0.0 ] 0.77 [ 0.18, 3.36 ] 2.04 [ 0.19, 21.82 ] 0.0 [ 0.0, 0.0 ] 1.45 [ 0.30, 7.02 ] 0.23 [ 0.01, 5.52 ] 0.72 [ 0.52, 0.99 ] 0.65 [ 0.38, 1.11 ]
Subtotal (95% CI)
3171
2829
0.82 [ 0.67, 1.01 ]
Total events: 170 (Exercise), 183 (Usual Care) Heterogeneity: Chi2 = 9.87, df = 15 (P = 0.83); I2 =0.0% Test for overall effect: Z = 1.87 (P = 0.061) 2 Follow-up longer than 12 months Andersen 1981 Bengtsson 1983 4/46 10/81 3/42 6/90
0.01 0.1 1 10 100
1.22 [ 0.29, 5.12 ] 1.85 [ 0.70, 4.87 ]
Favours exercise
Favours usual care
(Continued . . . )
70
(. . .
Study or subgroup Exercise n/N Carson 1982 Erdman 1986 Haskell 1994 Kallio 1979 Leizorovicz 1991 Shaw 1981 Sthle 1999 Toobert 2000 Vermeulen 1983 VHSG 2003 WHO 1983 Wilhelmsen 1975 Yu 2004 Zwisler 2008 12/151 4/40 3/145 41/188 0/60 15/323 5/56 1/17 2/47 2/98 169/1208 28/158 4/132 24/227 Usual Care n/N 21/152 0/40 3/155 56/187 4/61 24/328 3/53 0/11 5/51 1/99 169/1096 35/157 4/72 20/219 Risk Ratio M-H,Fixed,95% CI
Continued) Risk Ratio
M-H,Fixed,95% CI 0.58 [ 0.29, 1.13 ] 9.00 [ 0.50, 161.86 ] 1.07 [ 0.22, 5.21 ] 0.73 [ 0.51, 1.03 ] 0.11 [ 0.01, 2.05 ] 0.63 [ 0.34, 1.19 ] 1.58 [ 0.40, 6.28 ] 2.00 [ 0.09, 45.12 ] 0.43 [ 0.09, 2.13 ] 2.02 [ 0.19, 21.92 ] 0.91 [ 0.75, 1.10 ] 0.79 [ 0.51, 1.24 ] 0.55 [ 0.14, 2.12 ] 1.16 [ 0.66, 2.03 ]
Subtotal (95% CI)
2977
2813
0.87 [ 0.75, 0.99 ]
Total events: 324 (Exercise), 354 (Usual Care) Heterogeneity: Chi2 = 14.42, df = 15 (P = 0.49); I2 =0.0% Test for overall effect: Z = 2.04 (P = 0.041)
0.01
0.1
10
100
Favours exercise
Favours usual care
71
Analysis 1.2. Comparison 1 Exercise-based rehabilitation versus usual care, Outcome 2 Cardiovascular mortality.
Comparison: 1 Exercise-based rehabilitation versus usual care Outcome: 2 Cardiovascular mortality
Study or subgroup
Exercise n/N
Usual Care n/N
1 Follow-up of 6 to 12 months Bethell 1990 DeBusk 1994 Haskell 1994 Miller 1984 Ornish 1990 Schuler 1992 Sivarajan 1982 Vecchio 1981 WHO 1983 13/113 11/293 1/145 0/127 2/53 2/56 6/174 0/25 67/1208 12/116 9/292 0/155 2/71 1/40 0/57 2/84 2/25 71/1096 1.11 [ 0.53, 2.33 ] 1.22 [ 0.51, 2.90 ] 3.21 [ 0.13, 78.06 ] 0.11 [ 0.01, 2.31 ] 1.51 [ 0.14, 16.07 ] 5.09 [ 0.25, 103.66 ] 1.45 [ 0.30, 7.02 ] 0.20 [ 0.01, 3.97 ] 0.86 [ 0.62, 1.18 ]
Subtotal (95% CI)
2194
1936
0.93 [ 0.71, 1.21 ]
Total events: 102 (Exercise), 99 (Usual Care) Heterogeneity: Chi2 = 6.00, df = 8 (P = 0.65); I2 =0.0% Test for overall effect: Z = 0.53 (P = 0.59) 2 Follow-up longer than 12 months Belardinelli 2001 Dugmore 1999 Haskell 1994 Hofman-Bang 1999 Kallio 1979 La Rovere 2002 Shaw 1981 Specchia 1996 Toobert 2000 Vermeulen 1983 WHO 1983 Wilhelmsen 1975 0/59 2/62 2/145 1/48 35/188 6/49 14/323 5/125 1/17 2/47 144/1208 23/158 0/59 3/62 3/155 6/45 55/187 12/46 20/328 13/131 0/11 5/51 151/1096 33/157
0.005 0.1 1 10 200
0.0 [ 0.0, 0.0 ] 0.67 [ 0.12, 3.85 ] 0.71 [ 0.12, 4.20 ] 0.16 [ 0.02, 1.25 ] 0.63 [ 0.44, 0.92 ] 0.47 [ 0.19, 1.15 ] 0.71 [ 0.37, 1.38 ] 0.40 [ 0.15, 1.10 ] 2.00 [ 0.09, 45.12 ] 0.43 [ 0.09, 2.13 ] 0.87 [ 0.70, 1.07 ] 0.69 [ 0.43, 1.12 ]
Favours exercise
Favours usual care
(Continued . . . )
72
(. . .
Study or subgroup Exercise n/N Usual Care n/N Risk Ratio M-H,Fixed,95% CI
M-H,Fixed,95% CI
Subtotal (95% CI)
2429
2328
0.74 [ 0.63, 0.87 ]
0.005
0.1
10
200
Favours exercise
Favours usual care
Analysis 1.3. Comparison 1 Exercise-based rehabilitation versus usual care, Outcome 3 Fatal and/or nonfatal MI.
Comparison: 1 Exercise-based rehabilitation versus usual care Outcome: 3 Fatal and/or nonfatal MI
Study or subgroup
Exercise n/N
Usual Care n/N
1 Follow-up of 6 to 12 months Bertie 1992 Bethell 1990 DeBusk 1994 Giallauria 2008 Haskell 1994 Holmbck 1994 Kovoor 2006 Miller 1984 Schuler 1992 Seki 2008 Stern 1983 WHO 1983 0/57 9/113 10/293 1/30 4/145 2/34 3/72 5/127 0/56 0/18 1/42 56/1208 1/53 14/116 20/292 2/31 0/155 0/35 1/70 5/71 3/57 0/16 1/29 44/1096 0.31 [ 0.01, 7.46 ] 0.66 [ 0.30, 1.46 ] 0.50 [ 0.24, 1.05 ] 0.52 [ 0.05, 5.40 ] 9.62 [ 0.52, 177.06 ] 5.14 [ 0.26, 103.35 ] 2.92 [ 0.31, 27.37 ] 0.56 [ 0.17, 1.87 ] 0.15 [ 0.01, 2.75 ] 0.0 [ 0.0, 0.0 ] 0.69 [ 0.04, 10.60 ] 1.15 [ 0.78, 1.70 ]
Subtotal (95% CI)

Total events: 91 (Exercise), 91 (Usual Care)
2195
2021
0.92 [ 0.70, 1.22 ]
0.01
0.1
10
100
Favours exercise
Favours usual care
(Continued . . . )
73
(. . .
Study or subgroup Exercise n/N Heterogeneity: Chi2 = 12.30, df = 10 (P = 0.27); I2 =19% Test for overall effect: Z = 0.58 (P = 0.56) 2 Follow-up longer than 12 months Andersen 1981 Belardinelli 2001 Bengtsson 1983 Carson 1982 Dugmore 1999 Erdman 1986 Haskell 1994 Hofman-Bang 1999 Kallio 1979 La Rovere 2002 Leizorovicz 1991 Shaw 1981 Vermeulen 1983 WHO 1983 Wilhelmsen 1975 Zwisler 2008 3/46 1/59 2/81 13/151 7/62 2/40 4/145 0/48 34/188 0/49 4/60 16/323 4/47 122/1208 25/158 15/227 6/42 3/59 4/90 10/152 17/62 1/40 10/155 2/45 21/187 2/46 6/61 19/328 9/51 101/1096 28/157 10/219 Usual Care n/N Risk Ratio M-H,Fixed,95% CI
M-H,Fixed,95% CI
0.46 [ 0.12, 1.71 ] 0.33 [ 0.04, 3.11 ] 0.56 [ 0.10, 2.95 ] 1.31 [ 0.59, 2.89 ] 0.41 [ 0.18, 0.92 ] 2.00 [ 0.19, 21.18 ] 0.43 [ 0.14, 1.33 ] 0.19 [ 0.01, 3.81 ] 1.61 [ 0.97, 2.67 ] 0.19 [ 0.01, 3.81 ] 0.68 [ 0.20, 2.28 ] 0.86 [ 0.45, 1.63 ] 0.48 [ 0.16, 1.46 ] 1.10 [ 0.85, 1.41 ] 0.89 [ 0.54, 1.45 ] 1.45 [ 0.66, 3.15 ]
Subtotal (95% CI)
2892
2790
0.97 [ 0.82, 1.15 ]
Total events: 252 (Exercise), 249 (Usual Care) Heterogeneity: Chi2 = 20.00, df = 15 (P = 0.17); I2 =25% Test for overall effect: Z = 0.35 (P = 0.73)
0.01
0.1
10
100
Favours exercise
Favours usual care
74
Analysis 1.4. Comparison 1 Exercise-based rehabilitation versus usual care, Outcome 4 CABG.
Comparison: 1 Exercise-based rehabilitation versus usual care Outcome: 4 CABG
Study or subgroup
Exercise n/N
Usual Care n/N
Weight
1 Follow-up of 6 to 12 months Bertie 1992 Bck 2008 DeBusk 1994 Engblom 1996 Haskell 1994 Holmbck 1994 Kovoor 2006 Manchanda 2000 Miller 1984 Schuler 1992 Sivarajan 1982 Stern 1983 Sthle 1999 Vecchio 1981 1/57 1/21 42/293 1/119 3/145 0/34 2/72 0/21 9/127 1/56 11/174 1/42 4/56 0/25 0/53 0/16 33/292 1/109 6/155 1/35 6/70 6/21 3/71 1/57 8/84 0/29 6/53 1/25 0.7 % 0.7 % 41.9 % 1.3 % 7.3 % 1.9 % 7.7 % 8.2 % 4.9 % 1.3 % 13.7 % 0.7 % 7.8 % 1.9 % 2.79 [ 0.12, 67.10 ] 2.32 [ 0.10, 53.42 ] 1.27 [ 0.83, 1.94 ] 0.92 [ 0.06, 14.47 ] 0.53 [ 0.14, 2.10 ] 0.34 [ 0.01, 8.13 ] 0.32 [ 0.07, 1.55 ] 0.08 [ 0.00, 1.28 ] 1.68 [ 0.47, 6.00 ] 1.02 [ 0.07, 15.88 ] 0.66 [ 0.28, 1.59 ] 2.09 [ 0.09, 49.65 ] 0.63 [ 0.19, 2.11 ] 0.33 [ 0.01, 7.81 ]
Subtotal (95% CI)
1242
1070
100.0 %
0.91 [ 0.67, 1.24 ]
Total events: 76 (Exercise), 72 (Usual Care) Heterogeneity: Chi2 = 11.12, df = 13 (P = 0.60); I2 =0.0% Test for overall effect: Z = 0.59 (P = 0.55) 2 Follow-up longer than 12 months Belardinelli 2001 Haskell 1994 Hofman-Bang 1999 La Rovere 2002 Leizorovicz 1991 Shaw 1981 Specchia 1996 3/59 6/145 3/48 9/49 2/60 17/323 11/125 5/59 14/155 6/45 6/46 1/61 16/328 7/131
0.01 0.1 1 10 100
6.6 % 17.8 % 8.1 % 8.1 % 1.3 % 20.9 % 9.0 %
0.60 [ 0.15, 2.40 ] 0.46 [ 0.18, 1.16 ] 0.47 [ 0.12, 1.76 ] 1.41 [ 0.54, 3.65 ] 2.03 [ 0.19, 21.84 ] 1.08 [ 0.55, 2.10 ] 1.65 [ 0.66, 4.11 ]
Favours exercise
Favours usual care
(Continued . . . )
75
(. . .
Study or subgroup Exercise n/N Sthle 1999 Zwisler 2008 7/56 13/227 Usual Care n/N 7/53 14/219 Risk Ratio M-H,Fixed,95% CI 9.5 % 18.7 % Weight
M-H,Fixed,95% CI 0.95 [ 0.36, 2.52 ] 0.90 [ 0.43, 1.86 ]
Subtotal (95% CI)
1092
1097
100.0 %
0.93 [ 0.68, 1.27 ]
0.01
0.1
10
100
Favours exercise
Favours usual care
Analysis 1.5. Comparison 1 Exercise-based rehabilitation versus usual care, Outcome 5 PTCA.
Comparison: 1 Exercise-based rehabilitation versus usual care Outcome: 5 PTCA
Study or subgroup
Exercise n/N
Usual Care n/N
Weight
1 Follow-up of 6 to 12 months Bck 2008 DeBusk 1994 Haskell 1994 Kovoor 2006 Manchanda 2000 Schuler 1992 Sthle 1999 1/21 25/293 9/145 5/72 1/21 2/56 4/56 0/16 33/292 3/155 4/70 2/21 3/57 1/53 1.2 % 71.0 % 6.2 % 8.7 % 4.3 % 6.4 % 2.2 % 2.32 [ 0.10, 53.42 ] 0.75 [ 0.46, 1.24 ] 3.21 [ 0.89, 11.61 ] 1.22 [ 0.34, 4.34 ] 0.50 [ 0.05, 5.10 ] 0.68 [ 0.12, 3.91 ] 3.79 [ 0.44, 32.79 ]
Subtotal (95% CI)
664
664
100.0 %
1.02 [ 0.69, 1.50 ]
Total events: 47 (Exercise), 46 (Usual Care) Heterogeneity: Chi2 = 6.79, df = 6 (P = 0.34); I2 =12% Test for overall effect: Z = 0.09 (P = 0.93) 2 Follow-up longer than 12 months Belardinelli 2001 Haskell 1994 4/59 13/145 11/59 17/155
0.01 0.1 1 10 100
13.3 % 19.9 %
0.36 [ 0.12, 1.08 ] 0.82 [ 0.41, 1.62 ]
Favours exercise
Favours usual care
(Continued . . . )
76
(. . .
Study or subgroup Exercise n/N Hofman-Bang 1999 Specchia 1996 Sthle 1999 Zwisler 2008 10/48 1/125 8/56 38/227 Usual Care n/N 11/45 1/131 2/53 40/219 Risk Ratio M-H,Fixed,95% CI 13.8 % 1.2 % 2.5 % 49.3 % Weight
M-H,Fixed,95% CI 0.85 [ 0.40, 1.81 ] 1.05 [ 0.07, 16.57 ] 3.79 [ 0.84, 17.02 ] 0.92 [ 0.61, 1.37 ]
Subtotal (95% CI)
660
662
100.0 %
0.89 [ 0.66, 1.19 ]
0.01
0.1
10
100
Favours exercise
Favours usual care
Analysis 1.6. Comparison 1 Exercise-based rehabilitation versus usual care, Outcome 6 Hospital Admissions.
Comparison: 1 Exercise-based rehabilitation versus usual care Outcome: 6 Hospital Admissions
Study or subgroup
Exercise n/N
Usual Care n/N
Weight
1 Follow-up of 6 to 12 months Engblom 1996 Giallauria 2008 Hofman-Bang 1999 Lewin 1992 26/102 3/30 16/48 9/58 34/91 7/31 14/45 18/58 47.7 % 9.1 % 19.2 % 23.9 % 0.68 [ 0.45, 1.04 ] 0.44 [ 0.13, 1.55 ] 1.07 [ 0.59, 1.93 ] 0.50 [ 0.25, 1.02 ]
Subtotal (95% CI)
238
225
100.0 %
0.69 [ 0.51, 0.93 ]
Total events: 54 (Exercise), 73 (Usual Care) Heterogeneity: Chi2 = 3.39, df = 3 (P = 0.33); I2 =12% Test for overall effect: Z = 2.41 (P = 0.016) 2 Follow-up longer than 12 months Belardinelli 2001 Haskell 1994 11/59 62/145 21/59 72/155
0.01 0.1 1 10 100
6.2 % 20.6 %
0.52 [ 0.28, 0.99 ] 0.92 [ 0.71, 1.19 ]
Favours experimental
Favours control
(Continued . . . )
77
(. . .
Study or subgroup Exercise n/N Hofman-Bang 1999 Shaw 1981 VHSG 2003 Yu 2004 Zwisler 2008 19/48 109/323 11/98 34/132 95/227 Usual Care n/N 4/45 113/328 14/99 16/72 94/219 Risk Ratio M-H,Fixed,95% CI 1.2 % 33.3 % 4.1 % 6.1 % 28.4 % Weight
M-H,Fixed,95% CI 4.45 [ 1.64, 12.09 ] 0.98 [ 0.79, 1.21 ] 0.79 [ 0.38, 1.66 ] 1.16 [ 0.69, 1.95 ] 0.98 [ 0.79, 1.21 ]
Subtotal (95% CI)
1032
977
100.0 %
0.98 [ 0.87, 1.11 ]
0.01
0.1
10
100
Favours experimental
Favours control
ADDITIONAL TABLES
Table 1. Summary of health related quality of life (HRQL) scores at follow-up
Measure of HRQL
Mean (SD) outcome values at follow- P value up Exercise Usual Care
Difference between groups
Bell 1998 Nottingham health prole at 10.5 months follow-up: Energy Pain Emotional reactions Sleep Social isolation Physical mobility Belardinelli 2001 MOS at 6 months follow-up: 17.6 (27.1) 2.8 (8.8) 6.4 (17.0) 7.5 (18.4) 2.3 (10.6) 8.4 (11.1) 18.3 (29.8) 4.82 (11.9) 12.2 (19.9) 20.5 (27.8) 4.0 (13.3) 8.9 (14.5) 0.87** <0.05 <0.001 <0.001 0.37* 0.82** Exercise = Usual care Exercise > Usual care Exercise > Usual care Exercise > Usual care Exercise = Usual care Exercise = Usual care
78
(Continued)
PF RP BP GH VT SF RE MH
78 (19) 75 (13) 4 (9) 68 (14) NR 66 (10) NR 65 (12)
55 (20) 65 (14) 22 (10) 50 (19) NR 69 (12) NR 48 (15)
0.001 0.01 0.001 0.001
Exercise > Usual care Exercise > Usual care Exercise > Usual care Exercise > Usual care
0.14*
Exercise = Usual care
0.01
Exercise > Usual care
MOS at 12 months follow-up: PF RP BP GH VT SF RE MH Engblom 1992 Nottingham health prole at 5 years follow-up: Energy Pain Emotional reactions Sleep Social isolation 18 12 14 24 7 25 18 21 29 9 0.08 0.07 0.27 0.42 0.42 Exercise = Usual care Exercise = Usual care Exercise = Usual care Exercise = Usual care Exercise = Usual care 82 (18) 76 (9) 4 (9) 70 (14) NR 68 (11) NR 70 (14) 54 (20) 58 (14) 32 (12) 50 (18) NR 68 (12) NR 45 (15) 0.001 Exercise > Usual care 1.00* Exercise = Usual care 0.001 0.01 0.001 0.001 Exercise > Usual care Exercise > Usual care Exercise > Usual care Exercise > Usual care
79
(Continued)
Physical mobility Heller 1993
14
0.005
Exercise > Usual care
QLMI at 6 months follow-up: Emotional Physical Social Hofman-Bang 1999 AP-QLQ at 12 months follow-up: Physical activity Somatic symptoms Emotional distress Life satisfaction Oldridge 1991 QLMI at 4 months follow-up: Limitations Emotions 54 103 54 101 NS NS Exercise = Usual care Exercise = Usual care 4.9 NR NR NR 4.3 NR NR NR <0.05 NS NS NS Exercise > Usual care Exercise = Usual care Exercise = Usual care Exercise = Usual care 5.4 (1.1) 5.4 (1.2) 5.9 (1.1) 5.2 (1.2) 5.2 (1.3) 5.8 (1.1) 0.04 0.17* 0.35* Exercise > Usual care Exercise = Usual care Exercise = Usual care
QLMI at 8 months follow-up: Limitations Emotions 54 103 54 103 NS NS Exercise = Usual care Exercise = Usual care
QLMI at 12 months follow-up: Limitations Emotions Stahle 1999 Karolinska Questionnaire at 12 months follow-up: 54 105 55 102 NS NS Exercise = Usual care Exercise = Usual care
80
(Continued)
Chest pain Shortness of breath Dizziness Palpitation Cognitive ability Alertness Quality of sleep Physical ability Daily activity Depression Self perceived health Ladder of Life present Ladder of Life future Fitness Physical ability Toobert 2000
0.6 (1.2) 0.4 (1.1) -0.1 (1.1) -0.1 (1.0) -0.1 (0.6) 0.0 (0.9) 0.0 (0.5) 0.2 (0.7) 0.3 (0.5) 0.1 (0.3) 0.5 (1.3) 1.2 (1.2) 0.8 (2.7) 0.6 (1.4) 0.7 (1.0)
0.4 (1.3) 0.2 (1.0) 0.2 (0.9) 0.1 (0.9) 0.0 (0.7) 0.1 (0.8) 0.1 (0.5) 0.1 (0.4) 0.1 (0.5) 0.1 (0.2) 0.3 (1.0) 0.9 (1.8) 0.4 (2.3) 0.4 (1.0) 0.4 (1.1)
NS NS NS NS NS NS NS NS NS NS NS NS NS NS NS
Exercise = Usual care Exercise = Usual care Exercise = Usual care Exercise = Usual care Exercise = Usual care Exercise = Usual care Exercise = Usual care Exercise = Usual care Exercise = Usual care Exercise = Usual care Exercise = Usual care Exercise = Usual care Exercise = Usual care Exercise = Usual care Exercise = Usual care
SF-36 at 24 months follow-up: PF RP BP GH VT SF RE NR NR NR NR NR NR NR NR NR NR NR NR NR NR NS NS NS <0.05 NS <0.05 NS Exercise = Usual care Exercise = Usual care Exercise = Usual care Exercise > Usual care Exercise = Usual care Exercise > Usual care Exercise = Usual care
81
(Continued)
MH Yu 2003
NR
NR
NS
Exercise = Usual care
SF-36 at 8 months follow-up: PF RP BP GH VT SF RE MH 88 (12) 75 (33) 80 (25) 64 (26) 79 (18) 89 (27) 93 (18) 84 (16) 82 (17) 66 (35) 80 (25) 60 (28) 65 (17) 82 (28) 83 (35) 80 (15) 0.03* 0.18* 1.00* 0.45* 0.0001 0.15 0.05 0.20 Exercise > Usual care Exercise = Usual care Exercise = Usual care Exercise = Usual care Exercise > Usual care Exercise = Usual care Exercise = Usual care Exercise = Usual care
SF-36 at 24 months follow-up: PF RP BP GH VT SF RE MH Zwisler 2008 SF-36 at 12 months follow-up: PCS MCS 45.2 (9.8) 50.6 (10.8) 46.4 (9.8) 48.4 (11.5) 0.39* 0.16* Exercise = Usual care Exercise = Usual care 88 (13) 80 (32) 81 (21) 64 (20) 73 (21) 79 (30) 89 (25) 85 (14) 87 (9) 79 (30) 85 (20) 61 (18) 73 (17) 90 (18) 93 (25) 85 (12) 0.67* 0.87* 0.33* 0.43* 1.00* 0.04* 0.42* 1.00* Exercise = Usual care Exercise = Usual care Exercise = Usual care Exercise = Usual care Exercise = Usual care Exercise > Usual care Exercise = Usual care Exercise = Usual care
82
MOS=Medical Outcomes Study (MOS); Short Form-36 (SF-36); QLMI=Quality of Life After Myocardial Infarction questionnaire; AP-QLQ=Angina Pectoris-Quality of Life questionnaire; PF=physical problems; RP=role limitations because of physical problems; RE=role limitations because of emotional problems; VT=vitality; BP=bodily pain; SF=social functioning; MH=mental health; GH= general health perceptions; PCS=physical component summary; MCS=mental component summary; NR=not reported; NS=not signicant * Calculated by authors of this report based on independent two group t test. ** Adjusted for baseline difference between groups. Exercise = Usual care: no statistically signicant difference (P>0.05) between exercise and usual care groups at follow up Exercise > Usual care: statistically signicant difference (P=<0.05) between exercise and usual care groups at follow up
Table 2. Summary of costs of exercise-based rehabilitation and usual care
Variable Follow-up (months) Year of costs
Kovoor 2006 12 1999 ($AUD)
Marchionni 2003 14 2000 ($USD)
Yu 2004 24 2003 ($USD)
Mean cost of exercise-based rehabilitation (per patient): Exercise Usual Care Mean difference (95% CI) P value Costs considered $394 $0 $394 NR $5246 $0 $5246 NR NR $0 NR NR staff salary, equipment, investigations
assessments, counseling, educa- NR tion
Mean total healthcare costs (per patient): Exercise Usual Care Mean difference (95% CI) P value Additional considered healthcare NR NR NR NS, see below for details $17 272 $12 433 $4839 NR $15 292 $15 707 -$415 NS hospitalisations; revascularisations; private clinic visit; cardiac clinic visits; public noncardiac visits; casualty visits; drugs
costs phone calls (p=0.10); hospi- NR tal admissions (p=0.11); gated heart pool scan (p=0.50); exercise stress test (p=0.72); other diagnostics (p=0.37); visits to general practitioner (p=0.61), specialist doctor (p=0.35), or health-care professional (p=0. 31)
83
NR=not reported
Table 3. Results of univariate meta-regression analysis for total mortality
Explanatory variable
Exp(slope)*
95% Condence interval*
Proportion of variation ex- Interpretation plained 0% No evidence that relative risk is associated with case mix No evidence that relative risk is associated with case mix
Case mix (% MI patients)
RR=0.99
0.99 to 1.00
Dose of exercise (dose RR=1.00 =duration in weeks x number of sessions x number of sessions per week) Type of rehabilitation RR=0.92 (exercise only vs comprehensive rehab) Follow up (months) RR=0.99
1.00 to 1.00
0%
0.66 to 1.28
0%
No evidence that relative risk differs between types of rehabilitation No evidence that relative risk is associated with case mix No evidence that relative risk is associated with publication year
0.98 to 1.01
0%
Publication year (pre 1995 vs post 1995)
RR=0.80
0.54 to 1.20
0%
Table 4. Results of univariate meta-regression analysis for cardiovascular mortality
Exp(slope)*
Proportion of variation ex- Interpretation plained 0% No evidence that relative risk is associated with case mix No evidence that relative risk is associated with case mix
RR=1.01
0.98 to 1.04
1.00 to 1.00
0%
0.57to 1.23
0%
No evidence that relative risk differs between types of rehabilitation No evidence that relative risk is associated with case mix
0.98 to 1.00
0%
84
Table 4. Results of univariate meta-regression analysis for cardiovascular mortality
(Continued)
RR=1.37
0.73 to 2.22
0%
No evidence that relative risk is associated with publication year
Table 5. Results of univariate meta-regression analysis for total MI
Exp(slope)*
Proportion of variation ex- Interpretation plained 3.5% No evidence that relative risk is associated with case mix No evidence that relative risk is associated with case mix
RR=1.00
0.99 to 1.02
Dose of exercise (dose RR=1,00 =duration in weeks x number of sessions x number of sessions per week) Type of rehabilitation RR=0.87 (exercise only vs comprehensive rehab) Follow up (months) RR=0.99
1.00 to 1.00
0%
0.55 to 1.36
0.4%
0.98 to 1.01
6.3%
RR=1.38
0.82 to 2.33
0%
Table 6. Results of univariate meta-regression analysis for CABG
Exp(slope)*
RR=1.01
1.00 to 1.02
Dose of exercise (dose RR=1.00 =duration in weeks x number of sessions x number of sessions per week) Type of rehabilitation RR=1.13 (exercise only vs comprehensive rehab)
1.00 to 1.00
0%
0.67 to 1.93
0%
No evidence that relative risk differs between types of rehabilitation

85
Table 6. Results of univariate meta-regression analysis for CABG
(Continued)
Follow up (months)
RR=0.99
0.99 to 1.00
0%
No evidence that relative risk is associated with case mix No evidence that relative risk is associated with publication year
RR=0.84
0.50 to 1.42
0%
Table 7. Results of univariate meta-regression analysis for PTCA
Exp(slope)*
RR=0.99
1.00 to 1.01
1.00 to 1.00
0%
0.39 to 2.54
0%
0.99 to 1.02
0%
RR=0.92
0.42 to 2.06
0%
86
APPENDICES Appendix 1. Search strategies
CENTRAL, DARE and HTA 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20. 21. 22. 23. 24. MeSH descriptor Myocardial Ischemia explode all trees (myocard* NEAR isch*mi*) isch*mi* NEAR heart MeSH descriptor Coronary Artery Bypass explode all trees myocard* NEAR infarct* heart NEAR infarct* angina coronary NEAR (disease* OR bypass OR thrombo* OR angioplast*) MeSH descriptor Exercise Therapy explode all trees MeSH descriptor Sports, this term only MeSH descriptor Exertion explode all trees rehabilitat* (physical* NEAR (t* or train* or therap* or activit*)) MeSH descriptor Exercise explode all trees (train*) near (strength* or aerobic* or exercise*) ((exercise* or tness) NEAR/3 (treatment or intervent* or program*)) MeSH descriptor Rehabilitation explode all trees kinesiotherap* MeSH descriptor Physical Education and Training, this term only (#1 OR #2 OR #3 OR #4 OR #5 OR #6 OR #7 OR #8) (#9 OR #10 OR #11 OR #12 OR #13 OR #14 OR #15 OR #16 OR #17 OR #18 OR #19) (#20 AND #21) (#22), from 2001 to 2008 (#22), from 2008 to 2009
MEDLINE 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. exp Myocardial Ischemia/ (myocard* adj5 (ischaemia or ischemia)).tw. (isch?emi* adj5 heart).tw. exp Coronary Artery Bypass/ (myocard* adj5 infarct*).tw. (heart adj5 infarct*).tw. angina.tw. (coronary adj5 (disease* or bypass or thrombo* or angioplast*)).tw. or/1-8 exp Exercise Therapy/ Sports/ Physical Exertion/ rehabilitat*.mp. (physical* adj5 (t* or train* or therap* or activit*)).mp. exp Exercise/ (train* adj5 (strength* or aerobic* or exercise*)).tw. (train* adj5 (strength* or aerobic* or exercise*)).tw. ((exercise* or tness) adj3 (treatment or intervent* or program*)).tw. exp Rehabilitation/
87
20. 21. 22. 23. 24. 25. 26. 27. 28. 29. 30. 31. 32. 33. 34. 35. 36. 37. 38.
kinesiotherap*.tw. Physical Education and Training/ or/10-21 9 and 22 Randomized controlled trial.pt. randomized controlled trial/ (random$ or placebo$).ti,ab,sh. ((singl$ or double$ or triple$ or treble$) and (blind$ or mask$)).tw,sh. controlled clinical trial.pt. (retraction of publication or retracted publication).pt. trial.tw. groups.tw. drug therapy.sh. or/24-32 23 and 33 (200011* or 200012* or 2001* or 2002* or 2003* or 2004* or 2005* or 2006* or 2007* or 2008* or 2009*).ed. 34 and 35 (animals not humans).sh. 36 not 37
EMBASE 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20. 21. 22. 23. 24. 25. 26. 27. 28. 29. 30. 31. exp Coronary Artery Disease/ (MYOCARD* adj5 (ISCHAEMI* or ISCHEMI*)).ti,ab. ((ISCHAEMI* or ISCHEMI*) adj5 HEART).tw. Transluminal Coronary Angioplasty/ (CORONARY adj5 (DISEASE* or BYPASS* or THROMBO* or ANGIOPLAST*)).tw. exp Heart Infarction/ (MYOCARD* adj5 INFARCT*).tw. (HEART adj5 INFARC*).tw. Heart Muscle Revascularization/ exp Angina Pectoris/ ANGINA.tw. Coronary Artery Bypass Graft/ (CABG or PTCA).tw. or/1-13 rehabilitation/ rehabilitation center/ REHABIL*.tw. Sport/ exp kinesiotherapy/ exp exercise/ exp physiotherapy/ (PHYSICAL* adj5 (FIT* or TRAIN* or THERAP* or ACTIVIT*)).tw. (TRAIN* adj5 (STRENGTH* or AEROBIC or EXERCIS*)).tw. ((EXERCISE* or FITNESS) adj5 (TREATMENT or INTERVENT* or PROGRAM* or THERAPY)).tw. (AEROBIC* adj5 EXERCISE*).tw. (KINESIOTHERAPY or PHYSIOTHERAPY).tw. or/15-26 14 and 27 Randomized Controlled Trial/ (RANDOM* or PLACEBO*).tw. ((SINGL* or DOUBLE* or TRIPLE* or TREBLE*) and (BLIND* or MASK*)).tw.
88
32. 33. 34. 35. 36. 37. 38. 39. 40. 41.
Controlled Study/ controlled clinical trial/ or/29-33 28 and 34 (animal* not human*).sh,hw. 35 not 36 (2000* or 2001* or 2002* or 2003* or 2004* or 2005* or 2006* or 2007*).em. 37 and 38 (2008* or 2009*).em. 40 and 37
CINAHL 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20. 21. 22. 23. 24. 25. 26. 27. 28. 29. 30. 31. 32. 33. 34. 35. 36. 37. 38. 39. 40. (((MYOCARD* OR HEART) AND (ISCHAEMI* OR ISCHEMI*))).ti,ab CORONARY.ti,ab (((MYOCARD* OR HEART) AND INFARC*)).ti,ab ANGINA.ti,ab ((HEART AND FAILURE)).ti,ab ((HEART AND DISEAS*)).ti,ab ANGIOPLASTY, TRANSLUMINAL, PERCUTANEOUS CORONARY/ exp MYOCARDIAL ISCHEMIA/ CORONARY DISEASE/ exp MYOCARDIAL DISEASES/ exp MYOCARDIAL REVASCULARIZATION/ exp MYOCARDIAL INFARCTION/ ANGINA-PECTORIS.ti,ab 1 OR 2 OR 3 OR 4 OR 5 OR 6 OR 7 OR 8 OR 9 OR 10 OR 11 OR 12 OR 13 exp REHABILITATION/ exp SPORTS/ exp EXERCISE/ PHYSICAL ACTIVITY/ exp AEROBIC EXERCISES/ exp PHYSICAL FITNESS/ exp PATIENT EDUCATION/ exp THERAPEUTIC EXERCISE/ REHABILITAT*.ti,ab ((PHYSICAL* AND (FIT OR FITNESS OR TRAIN* OR THERAP* OR ACTIVIT*))).ti,ab ((TRAIN*) AND (STRENGTH* OR AEROBIC OR EXERCIS*)).ti,ab (((EXERCISE* OR FITNESS) AND (TREATMENT OR INTERVENT* OR PROGRAM* OR THERAPY))).ti,ab (PATIENT* AND NEAR AND EDUCAT*).ti,ab (((LIFESTYLE OR LIFE-STYLE) AND (INTERVENT* OR PROGRAM* OR TREATMENT*))).ti,ab 15 OR 16 OR 17 OR 18 OR 19 OR 20 OR 21 OR 22 OR 23 OR 24 OR 25 OR 26 OR 27 OR 28 14 AND 29 30 [Limit to: Publication Year 2001-2007] 30 [Limit to: Publication Year 2008-2009] exp CLINICAL TRIALS/ OR CLINICAL TRIAL REGISTRY/ ((RANDOM* OR PLACEBO*)).ti,ab ((SINGL* OR DOUBLE* OR TRIPLE* OR TREBLE*) AND (BLIND* OR MASK*)).ti,ab (CONTROLLED ADJ CLINICAL ADJ TRIALS).ti,ab 31 [Limit to: (Publication Type Clinical Trial) and Publication Year 2001-2007] [Limit to: (Publication Type Clinical Trial) and Publication Year 2008-2009] 33 OR 34 OR 35 OR 36 31 AND 39 [Limit to: Publication Year 2001-2007]
89
41. 32 AND 39 [Limit to: Publication Year 2008-2009] Science Citation Index Expanded (SCI-EXPANDED) 1. 2. 3. 4. 5. 6. 7. ((myocard*) SAME (isch?emia or infarct* or revasculari?*)) ((coronary* or heart*) SAME (by?pass or disease*)) ((heart) SAME (infarct* or isch?emia or failure or attack)) (angina or cardiac* or PTCA or CABG) #1 or #2 or #3 or #4 (rehab* or educat*) #5 AND #6
WHATS NEW
Last assessed as up-to-date: 13 June 2010.
Date 4 July 2011
Event Amended
Description Author (Neil Oldridge) details updated
HISTORY
Protocol rst published: Issue 3, 1999 Review rst published: Issue 4, 2000
Date 7 June 2011
Event New search has been performed
Description The searches were updated and re-run in December 2009, identifying an additional 17 studies for inclusion. Fourty-seven trials in total have been included The inclusion criteria have been revised for this update. Five out of the 35 formerly included studies (in the review) have therefore been excluded The conclusions have changed based on the analysis of 47 included studies and have focused more on the impact of exercise-based cardiac rehabilitation on clinical events and HRQL outcomes Substantive amendment
7 June 2011
New citation required and conclusions have changed
1 November 2000
New citation required and conclusions have changed
90
CONTRIBUTIONS OF AUTHORS
All authors were involved in the conception and design of the update review. Tiffany Moxham developed the search strategy. BSH and JMHC performed study selection, data extraction and risk of bias assessment. BSH and RST wrote the rst draft of the update review, and all co-authors contributed to review and editing all additional drafts of the report. All authors approved the nal manuscript.
DECLARATIONS OF INTEREST
RST, JJ, SE, KR, NO, DT were authors of the original Cochrane review. RST has been a co-investigator on a number of trials of cardiac rehabilitation.
SOURCES OF SUPPORT Internal sources

No sources of support supplied
External sources
NIHR, UK Cochrane Collaboration Programme Grant, UK.
DIFFERENCES BETWEEN PROTOCOL AND REVIEW
Changes in this update review

Given its policy focus, in addition to updating the original Cochrane review, this update review: 1. Excluded exercise capacity and cardiac risk factors outcomes and added costs. 2. Limited the inclusion to those studies that assess outcomes at six months or longer.
NOTES
This review was supported by a National Institute for Health Research (NIHR) Cochrane Collaboration Programme Grant (CPGS10).
INDEX TERMS Medical Subject Headings (MeSH)

Exercise Therapy; Coronary Disease [mortality; rehabilitation]; Health Status; Myocardial Infarction [mortality; rehabilitation]; Myocardial Revascularization [statistics & numerical data]; Outcome Assessment (Health Care); Quality of Life; Randomized Controlled Trials as Topic
91
MeSH check words

Female; Humans; Male
92

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Exercise-based cardiac rehabilitation for coronary heart disease (Review)

Exercise-based cardiac rehabilitation for coronary heart disease

Description of the intervention

Description of the condition

How the intervention might work

Why it is important to do this review

Criteria for considering studies for this review

CABG PTCA Restenting Total hospitalisations Cardiovascular hospitalisations Other hospitalisations

Search methods for identication of studies

Data collection and analysis

Figure 1. Study ow diagram

Risk of bias in included studies

Characteristics of included interventions

Summary of main results

AUTHORS CONCLUSIONS Implications for practice

Implications for research

Quality of the evidence

References to studies included in this review

References to studies excluded from this review

References to studies awaiting assessment

References to ongoing studies

References to other published versions of this review

Characteristics of included studies [ordered by study ID]

Not reported. Unclear in terms of assessment of outcomes.

15% lost to follow-up, no description of withdrawals or dropouts No information reported.

Notes Risk of bias Bias Authors judgement Support for judgement

Random sequence generation (selection Low risk bias)

Allocation concealment (selection bias)

Not reported. Unclear in terms of assessment of outcomes.

Selective reporting (reporting bias)

Not reported. Unclear in terms of assessment of outcomes.

24% lost to follow-up, no description of withdrawals or dropouts No information reported.

Not reported. Unclear in terms of assessment of outcomes.

16% lost to follow up, no description of withdrawals or dropouts

Selective reporting (reporting bias)

Outcomes Notes Risk of bias Bias

Support for judgement randomised

Not reported. Unclear in terms of assessment of outcomes.

8.1% lost to follow-up, no description of withdrawals or dropouts No information reported.

Not reported. Unclear in terms of assessment of outcomes.

<20% lost to follow up, no description of withdrawals or dropouts

Selective reporting (reporting bias)

Notes Risk of bias Bias

Support for judgement randomly allocated

Not reported. Unclear in terms of assessment of outcomes.

21% lost to follow up, no description of withdrawals or dropouts No information reported.

Outcomes Notes Risk of bias Bias

Support for judgement randomly allocated

Not reported. Unclear in terms of assessment of outcomes.

Not reported. Not reported.

All patients accounted for.

29 % lost to follow up, no description of withdrawals or dropouts No information reported.

Outcomes Notes Risk of bias Bias

Support for judgement randomized

Support for judgement randomly subdivided

Not reported. Unclear in terms of assessment of outcomes.

32% lost to follow up, no description of withdrawals or dropouts No information reported.

Outcomes Notes Risk of bias Bias

Support for judgement randomized