Thrombosis Research 130 (2012) 390–395

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Thrombosis Research
journal homepage: www.elsevier.com/locate/thromres

Regular Article

Clinical outcome of stable outpatients with coronary, cerebrovascular or peripheral

artery disease, and atrial fibrillation
Eduardo Aguilar a, Ana María García-Díaz b, Juan Francisco Sánchez Muñoz-Torrero c,
Lorenzo Ramón Álvarez d, Mar Piedecausa e, Gemma Arnedo f, Manuel Monreal g,⁎
and the FRENA Investigators 1
a
Department of Internal Medicine, Hospital de Alcañiz, Alcañiz, Teruel, Spain
b
Primary Healthcare, ABS Gaudi, Barcelona, Spain
c
Department of Internal Medicine, Hospital San Pedro de Alcántara, Cáceres, Spain
d
Department of Vascular Surgery, Hospital de Terrassa, Terrasa, Barcelona, Spain
e
Department of Internal Medicine, Hospital General Universitario de Elche, Elche, Alicante, Spain
f
Department of Vascular Surgery, Hospital Universitari Germans Trias i Pujol, Badalona, Barcelona, Spain
g
Department of Internal Medicine, Hospital Universitari Germans Trias i Pujol, Badalona, Barcelona, Spain

a r t i c l e i n f o a b s t r a c t

Article history: Background: The influence of atrial fibrillation (AF) on outcome in patients with symptomatic atherosclerotic
Received 14 March 2012 disease has not been thoroughly studied.
Received in revised form 7 May 2012 Methods: FRENA is an ongoing registry of stable outpatients with coronary (CAD), cerebrovascular (CVD), or
Accepted 11 May 2012 peripheral (PAD) artery disease. With the aim to guide therapy, we assessed the incidence of subsequent
Available online 31 May 2012
myocardial infarction (MI), ischemic stroke or major bleeding in patients with AF, according to initial presen-
tation.
Keywords:
Atrial fibrillation
Results: As of June 2011, 3848 patients were recruited: 1436 had CAD, 1104 CVD, and 1308 had PAD. Of these,
Ayocardial infarction 470 (12%) had AF: 151 patients with CAD, 157 with CVD, and 162 with PAD. Over a mean follow-up of 16 ±
Atroke 13 months, 19 patients with AF developed acute MI, 22 ischemic stroke and 7 bled. Among AF patients with
Bleeding CAD, the incidence of subsequent MI (5.00 events per 100 patient-years; 95% CI: 2.54-8.91) was non-
Antiplatelets significantly higher than that of stroke (1.48; 95% CI: 0.38-4.04) or major bleeding (1.47; 95% CI: 0.37-
Anticoagulants 4.01). Among those with CVD, the incidence of stroke (5.61; 95% CI: 2.95-9.75) exceeded that of MI (no
events) or major bleeding (0.51; 95% CI: 1.24-6.36). Among those with PAD, the incidence of MI (4.41; 95%
CI: 2.15-8.10) and stroke (3.93; 95% CI: 1.82-7.46) were similar.
Conclusions: CAD patients with AF are at a higher risk of subsequent MI than of stroke. Among those with
CVD, the risk of stroke far exceeds that of MI. Those with PAD have a high and similar risk for both events.
© 2012 Elsevier Ltd. All rights reserved.

Introduction anticoagulants has been paralleled by an increased incidence of bleed-

ing complications [9–11].
Patients with symptomatic atherosclerotic disease are at high risk of Current estimates of the occurrence of subsequent ischemic
subsequent ischemic events, including acute myocardial infarction (MI) events and bleeding complications in patients with symptomatic ath-
and stroke [1–3]. In these patients, antiplatelet therapy results in a erosclerotic disease and AF are not frequently available. Thus, in clin-
significant reduction in all-cause mortality, vascular mortality, and ical practice a substantial proportion of patients with atherosclerotic
non-fatal AMI and stroke [4]. Systemic anticoagulation is not indicated, disease and AF may receive suboptimal therapy [12,13]. A better
but it may be considered in selected patients, including those with atrial understanding of the pattern of recurrence of further vascular events
fibrillation (AF) [5,6], since anticoagulant therapy is highly effective in and of bleeding might be helpful for better targeting existing treat-
preventing stroke in AF patients [7,8]. However, the reduced risk of ments in these high-risk patients [14].
ischemic events associated with the combination of antiplatelets and The FRENA (Factores de Riesgo y ENfermedad Arterial) Registry was
initiated in March 2003 to prospectively record the current clinical
management and outcome of stable outpatients with atherosclerotic
⁎ Corresponding author at: Servicio de Medicina Interna, Hospital Universitari disease in Spanish hospitals. It is an ongoing, multicenter, observational
Germans Trias i Pujol, 08916 Badalona (Barcelona), Spain. Tel.: + 34 669675313; fax:
+ 34 934978843.
registry of consecutive patients designed to gather and analyze data on
E-mail address: mmonreal.germanstrias@gencat.cat (M. Monreal). treatment patterns and outcomes in patients with symptomatic
1
A full list of FRENA investigators is given in the appendix. ischemic disease of the heart, brain, and/or major peripheral arteries.

0049-3848/$ – see front matter © 2012 Elsevier Ltd. All rights reserved.
doi:10.1016/j.thromres.2012.05.016
 E. Aguilar et al. / Thrombosis Research 130 (2012) 390–395 391

Data from this registry have been used to study the influence of body and blood pressure on standard conditions, after 5 minutes of rest. An
weight, alcohol consumption, renal function, glucose control, or use of electrocardiogram was also recorded. After the initial visit, patients
some drugs on outcome [14–18]. The aim of the current study was to as- were followed-up at 4-month intervals for at least 12 months. At
sess the incidence of subsequent ischemic events (i.e., MI or ischemic these visits, any change in medical history and data from physical ex-
stroke) and major bleeding complications in patients with coronary amination were recorded, with special attention to risk factors; labora-
(CAD), cerebrovascular (CVD) or peripheral (PAD) artery disease and tory tests; the type, dose, and duration of treatment received, and
AF. clinical outcome. If AF was suspected on physical examination (on the
basis of irregular pulse, irregular jugular venous pulsations, or varia-
Patients and Methods tions in the intensity of the first heart sound), an electrocardiogram
was performed. Physicians were allowed to use any and all appropriate
Inclusion Criteria medications, as dictated by their usual clinical practice patterns.

Participating hospitals in the FRENA registry prospectively enrolled Data Collection

consecutive outpatients with symptomatic artery disease with at least
one recent (b3 months prior to enrollment) episode of coronary artery The attending physicians ensured that eligible patients were con-
disease (CAD), cerebrovascular (CVD), or peripheral artery disease secutively enrolled. Data were recorded on to a computer-based case
(PAD), either intermittent claudication with an ankle-brachial index report form at each participating hospital and submitted to a central-
b0.9, or previous vascular intervention or limb amputation for PAD). ized coordinating centre through a secure website. Patient identities
The Fontaine classification was used for categorization of PAD [19]. All remain confidential because they were identified by a unique number
patients provided oral consent to their participation in the registry, assigned by the study coordinating centre, which was responsible for
according to the requirements of the ethics committee within each all data management. Data quality was regularly monitored and doc-
hospital. umented electronically to detect inconsistencies or errors, which are
resolved by the local coordinators. Data quality was also monitored
Study Design by periodic visits to participating hospitals, by contract research orga-
nizations that compared the medical records with the data in the
At baseline, data on demographics, risk factors, co-morbidities, web. A data audit was performed at periodic intervals.
and drug therapy were collected. Patients were considered to have
AF if they had confirmed AF at enrollment or had had at least two ep- Statistical Analysis
isodes of intermittent AF in the previous year. The primary outcome
was the incidence of subsequent MI, ischemic stroke, or major bleed- Categorical variables were compared using the chi-square test
ing. MI was defined as a transient increase of creatine-kinase-MB or (two-sided). Incidence rates were calculated as cumulative incidence
troponin in patients with ischemic symptoms and/or typical electro- (events/100 patient-years) and compared using the rate ratio [23].
cardiogram signs (development of pathologic Q-waves or ST- We used Kaplan-Meier plot to estimate with the risk to develop sub-
segment elevation or depression). Ischemic stroke was diagnosed if sequent ischemic events in patients with AF. Statistical analyses were
the patient had an appropriate clinical event not resolving completely conducted with SPSS for Windows Release 17.0 (SPSS, Inc).
within 24 hours, and had a brain CT or MRI that showed a compatible
low-density lesion. Bleeding complications were classified as ‘major’ Results
if they were overt and required a transfusion of 2 units of blood or
more, or if they were retroperitoneal, spinal or intracranial, or when As of June 2011, 3848 patients were recruited in FRENA: 1436
they were fatal. A patient was classified as having diabetes when had CAD (myocardial infarction 1075, angina 361), 1104 had CVD
there was a clinical history of diabetes or when they were taking in- (ischemic stroke 944, transient ischemic attack 160), and 1308 had
sulin or oral antidiabetic agents. Patients were classified as having hy- PAD (Fontaine stage II 1043, stage III 121, stage IV 144). Of these,
pertension when there was a clinical history of hypertension or when 470 patients (12%) had AF (151 patients with CAD, 157 with CVD,
they were taking antihypertensive medications. Creatinine clearance and 162 with PAD). Patients with AF were 9 years older, more likely
was calculated according to the Cockcroft and Gault formula [20]. female, and more likely had chronic lung disease, heart failure,
diabetes or hypertension than those with sinus rhythm (Table 1).
Risk Stratification Scores During follow-up, patients with AF had higher mean systolic blood
pressure levels, heart rate, and lower LDL-cholesterol and creatinine
We evaluated the CHA2DS2VASC and the HAS-BLED scores in all clearance levels. They more likely received digoxin, diuretics, angiotensin-
patients. The CHA2DS2VASC score is expressed as a point based scor- II antagonists, calcium antagonists or anticoagulants, and less likely re-
ing system from 0 to 9, whereby 0 = low risk, 1 = intermediate, and ceived beta-blockers, antiplatelets or statins. One in every 4 patients
≥2 is high risk [21]. International guidelines recommend that all pa- with AF received amiodarone, one in every 3 received antiplatelets (aspi-
tients assessed as high risk and most patients at moderate risk with rin, clopidogrel, or both), one in every 3 anticoagulants, and one in every 3
this score are offered oral anticoagulants, unless it is contraindicated received both antiplatelets and anticoagulants. Among patients with
or not tolerated [6]. The HAS-BLED score is also expressed as a point sinus rhythm, 90% received antiplatelets, 2.8% anticoagulants, and 4.6%
based scoring system from 0 to 9, whereby 0-2 = low risk, and ≥3 received both antiplatelets and anticoagulants.
is measurable risk [22].
Outcome in Patients With or Without AF
Follow-up
Over a mean follow-up of 16 ± 13 months (range, 2–45 months),
A detailed history was performed on all patients at study entry (less 108 patients subsequently suffered MI, 104 ischemic stroke, 27 had a
than 3 months after an acute ischemic episode). Co-morbid conditions major bleeding event (in the gastrointestinal tract 14, brain 7, other
were characterized, including a history of CAD, CVD or PAD, diabetes, 6), and 205 died. Nineteen patients with subsequent MI (18%), 18
hypertension, hyperlipidemia, chronic lung disease, chronic heart fail- with stroke (17%), and 7 with major bleeding (26%) died within
ure, cancer, smoking status and alcohol consumption. Then, physical ex- 15 days of the events. Patients with AF had a significantly higher inci-
amination was performed comprising body weight, height, heart rate dence of subsequent stroke, major bleeding and death, and a non-
392 E. Aguilar et al. / Thrombosis Research 130 (2012) 390–395

Table 1 Table 2
Clinical characteristics of the patients. Incidence of subsequent events per 100 patient-years (and 95% confidence intervals) in
3,848 patients, according to initial presentation and the presence or absence of atrial
Atrial fibrillation Sinus rhythm p value fibrillation.
Patients, N 470 3378
Atrial Sinus Rate ratio p
Clinical characteristics,
fibrillation rhythm (95% CI) value
Mean age (years ± SD) 74 ± 9 65 ± 12 b 0.001
Gender (males) 280 (60%) 2577 (76%) b 0.001 All patients, N 470 3378
Body mass index (mean ± SD) 29 ± 5 28 ± 6 0.073 Follow-up (years) 609.7 4549.6
Underlying diseases, Myocardial 3.17 1.98 1.60 (0.95-2.58) 0.062
Cancer 27 (5.7%) 191 (5.7%) 0.937 infarction (1.96-4.85) (1.60-2.43)
Chronic lung disease 102 (22%) 458 (14%) b 0.001 Ischemic stroke 3.68 1.82 2.02 (1.24-3.20) 0.003
Chronic heart failure 122 (26%) 180 (5.3%) b 0.001 (2.37-5.49) (1.46-2.25)
Diabetes 210 (45%) 1290 (38%) 0.006 Major bleeding 1.49 0.40 3.75 (1.61-8.28) b 0.001
Hypertension 380 (81%) 2274 (67%) b 0.001 (0.73-2.73) (0.24-0.61)
Current smokers 35 (7.4%) 760 (23%) b 0.001 Overall death 7.38 3.52 2.10 (1.50-2.91) b 0.001
Clinical presentation, (5.45-9.79) (3.00-4.09)
Coronary artery disease 151 (32%) 1285 (38%) 0.013 CAD patients, N 151 1285
Cerebrovascular disease 157 (33%) 947 (28%) 0.016 Follow-up (years) 205.5 1726.1
Peripheral artery disease 162 (35%) 1146 (34%) 0.816 Myocardial 5.00 3.13 1.60 (0.77-3.05) 0.171
Physical examination, infarction (2.54-8.91) (2.37-4.06)
Mean SBP levels (mm Hg) 137 ± 16 136 ± 20 0.258 Ischemic stroke 1.48 0.64 2.32 (0.52-7.85) 0.183
Mean DBP levels (mm Hg) 74 ± 9 75 ± 9 0.178 (0.38-4.04) (0.34-1.11)
Mean heart rate (bpm) 75 ± 11 72 ± 11 b 0.001 Major bleeding 1.47 0.17 8.49 (1.46-49.42) 0.002
Mean laboratory levels, (0.37-4.01) (0.04-0.47)
Creatinine clearance (mL/min) 56 ± 26 73 ± 32 b 0.001 Overall death 8.27 2.72 3.05 (1.71-5.24) b 0.001
Total cholesterol (mg/dL) 175 ± 37 179 ± 36 0.065 (4.98-13.0) (2.02-3.59)
LDL-cholesterol (mg/dL) 103 ± 30 106 ± 31 0.034 CVD patients, N 157 947
Drugs, Follow-up (years) 196.1 1266.6
Amiodarone 119 (25%) 0 b 0.001 Myocardial 0 0.72 0.00 (0.00-2.53) 0.236
Digoxin 121 (26%) 19 (0.6%) b 0.001 infarction (0.35-1.32)
Diuretics 293 (62%) 1165 (35%) b 0.001 Ischemic 5.61 3.96 1.45 (0.72-2.73) 0.259
Beta-blockers 165 (35%) 1367 (41%) 0.026 stroke (2.95-9.75) (2.96-5.19)
ACE-inhibitors 203 (43%) 1513 (45%) 0.514 Major bleeding 0.51 0.32 1.61 (0.07-12.84) 0.666
Angiotensin-II antagonists 179 (38%) 992 (29%) b 0.001 (0.26-2.53) (0.10-0.76)
Calcium antagonists 160 (34%) 861 (26%) b 0.001 Overall death 3.06 4.03 0.76 (0.30-1.68) 0.523
Antiplatelets alone 169 (36%) 3026 (90%) b 0.001 (1.24-6.36) (3.03-5.25)
Anticoagulants alone 160 (34%) 95 (2.8%) b 0.001 PAD patients, N 162 1146
Antiplatelets and anticoagulants 141 (30%) 155 (4.6%) b 0.001 Follow-up (years) 208.1 1556.8
Statins 319 (68%) 2728 (81%) b 0.001 Myocardial 4.41 1.76 ( 0.25 (0.01-0.52) 0.013
Insulin 79 (17%) 463 (14%) 0.070 infarction (2.15-8.10) 1.18-2.52)
Oral antidiabetics 148 (32%) 923 (27%) 0.059 Ischemic stroke 3.93 1.43 0.28 (0.12-0.61) 0.010
(1.82-7.46) (0.92-2.13)
Abbreviations: SD, standard deviation; SBP, systolic blood pressure; DBP, diastolic
Major bleeding 2.43 0.71 0.34 (0.11-0.98) 0.015
blood pressure; ACE, angiotensin-converting enzyme.
(0.89-5.40) (0.37-1.23)
Overall death 10.6 3.98 0.27 (0.16-0.43) b 0.001
(6.79-15.7) (3.08-5.07)

significantly higher incidence of MI than those with sinus rhythm Abbreviations: CAD, coronary artery disease; CVD, cerebrovascular disease; PAD,
(Table 2). Interestingly however, MI was the most common subsequent peripheral artery disease; CI, confidence intervals.
event among patients with CAD (with or without AF), while ischemic
stroke was the most common event among those with CVD (with or antiplatelets concomitantly) was similar in patients scoring ≤2 points
without AF). Among patients with PAD, the two events were similarly (44 of 64, 69%) to those scoring >2 points (257 of 406, 63%).
common. The incidence of subsequent stroke rose from no events in patients
scoring ≤2 points using the CHA2DS2VASC score to 6.87 events per
100 patient-years (95% CI: 3.67-11.5) in those scoring >5 points, but
Outcome in Patients With AF the incidence of subsequent MI did not increase with the CHA2DS2VASC
score. The incidence of major bleeding progressively increased with the
When only considering patients with AF, the incidence of subse- HAS-BLED score, from zero events in patients scoring ≤2 points to 2.59
quent MI (3.17 events per 100 patient-years) was similar to that of (95% CI: 0.82-6.25) in those scoring over 4 points.
stroke (3.68 events), as shown in Table 2. However, CAD patients
more frequently suffered MI (Fig. 1), those with CVD more frequently
had ischemic stroke (Fig. 2), and those with PAD had a high and sim- Discussion
ilar incidence of both MI and stroke (Fig. 3). Among patients with
CAD, the incidence of subsequent stroke was similar to that of Patients with previous vascular events are at high risk of other
major bleeding, while in those with CVD the incidence of subsequent vascular events, though somewhat less than for the same event
stroke was over 10 times higher than that of major bleeding (Table 2). [24–27]. In the current analysis, the incidence of subsequent MI in pa-
Using the CHA2DS2VASC score, 35 patients (7.4%) scored ≤2 points, tients with CAD was up to 5 times higher than that of ischemic stroke
275 (59%) scored 3–5 points, and 160 (34%) scored >5 points (Table 3). (3.13 vs. 0.64 events per 100 patient-years) if they had sinus rhythm,
The proportion of patients receiving anticoagulants (with or without and 3.4 times higher (5.00 vs. 1.48 events) in those with AF. Among
antiplatelets concomitantly) was lower in patients scoring ≤2 points patients with CVD, the incidence of subsequent stroke far exceeded
(16 of 35, 46%) than in those scoring >2 points (285 of 435, 66%). that of MI, both in patients with sinus rhythm (3.96 vs. 0.72 events)
Using the HAS-BLED score, 64 patients (14%) scored ≤2 points, 283 or AF (5.61 vs. no event). Finally, among patients with PAD the inci-
(60%) scored 3–4 points, and 123 (26%) scored >4 points (Table 3). dence of MI and stroke was similar, both in patients with sinus
The proportion of patients receiving anticoagulants (with or without rhythm (1.76 vs. 1.43 events) and in those with AF (4.41 vs. 3.93
 E. Aguilar et al. / Thrombosis Research 130 (2012) 390–395 393

10%

Cumulative Incidence (%)

9% Myocardial infarction
8%
Ischemic stroke
7%
6%
5%
4%
3%
2%
1%
0%

10

12

14

16

18

20

22

24
0

8
Months

0-3 3-6 6-9 9-12 12-15 15-18 18-21 21-24

months months months months months months months months
Patients at risk 146 131 117 97 64 36 26 23
Myocardial infarction
Events 6 2 0 1 0 0 0 0
Patients at risk 146 136 121 99 64 36 26 22
Ischemic stroke
Events 0 1 0 1 0 0 0 0

Fig. 1. Cumulative incidence of subsequent events in patients with coronary artery disease.

16%
Cumulative Incidence (%)

14%
Myocardial infarction
12%
Ischemic stroke
10%

8%

6%

4%

2%

0%
10

12

14

16

18

20

22

24
0

Months

0-3 3-6 6-9 9-12 12-15 15-18 18-21 21-24

months months months months months months months months
Patients at risk 152 141 129 106 66 36 25 21
Myocardial infarction
Events 0 0 0 0 0 0 0 0
Patients at risk 152 138 125 102 63 36 25 21
Ischemic stroke
Events 3 2 1 2 0 0 1 0

Fig. 2. Cumulative incidence of subsequent events in patients with cerebrovascular disease.

events). One in every 7 patients with subsequent events died of the stroke prevention against recurrent MI or stent thrombosis, versus the
recurrent event. Thus, its clinical impact is considerable. harm of bleeding with combination antithrombotic therapy. Unfortu-
Current guidelines recommend the use of aspirin-clopidogrel com- nately, there is a lack of published evidence on what is the optimal man-
bination therapy after acute coronary syndrome and/or percutaneous agement strategy in such AF patients. A recent consensus document
coronary interventions [28,29]. In patients with AF, where there is the suggests the use of dual antiplatelet therapy plus anticoagulation for
requirement for long-term anticoagulation, there is the need to balance at least one month, and then anticoagulation plus single antiplatelet
Cumulative Incidence (%)

10%

8%

6%

4% Myocardial infarction

2% Ischemic stroke

0%
10

12

14

16

18

20

22

24
0

Months

0-3 3-6 6-9 9-12 12-15 15-18 18-21 21-24

months months months months months months months months
Patients at risk 159 149 138 121 85 49 36 28
Myocardial infarction
Events 1 1 3 2 2 0 0 0
Patients at risk 159 148 136 117 83 49 38 30
Ischemic stroke
Events 2 1 4 0 1 0 0 0

Fig. 3. Cumulative incidence of subsequent events in patients with peripheral artery disease.
394 E. Aguilar et al. / Thrombosis Research 130 (2012) 390–395

Table 3
Clinical characteristics, antithrombotic therapy and outcome in 470 patients with atrial fibrillation, according to their risk of subsequent ischemic events and for bleeding.

CHA2DS2VASc ≤2 CHA2DS2VASc 3 to 5 points CHA2DS2VASc >5 HAS-BLED ≤ 2 points HAS-BLED 3 to 4 points HAS-BLED >4 points
points points

All patients, N 35 (7.4%) 275 (59%) 160 (34%) 64 (14%) 283 (60%) 123 (26%)
Initial presentation,
CAD 14 (9.3%) 83 (55%) 54 (36%) 21 (13%) 105 (70%) 25 (17%)
CVD 1 (0.6%) 89 (57%) 67 (43%) 7 (4.5%) 75 (48%) 75 (48%)
PAD 20 (12%) 103 (64%) 39 (24%) 36 (22%) 103 (64%) 23 (14%)
Treatment,
Antiplatelets 19 (11%) 92 (54%) 58 (34%) 20 (12%) 100 (59%) 49 (29%)
Anticoagulants 7 (4.4%) 97 (61%) 56 (35%) 30 (19%) 120 (75%) 10 (6.2%)
Both 9 (6.4%) 86 (61%) 46 (33%) 14 (9.9%) 63 (45%) 64 (45%)
Outcome,
Myocardial 4.07 (0.68-13.4) 1.34 (0.49-2.97) 6.77 (3.67-11.5) 4.41 (1.40-10.6) 3.09 (1.63-5.37) 2.60 (0.83-6.28)
infarction
Ischemic stroke 0 2.69 (1.37-4.80) 6.87 (3.72-11.7) 3.25 (0.83-8.85) 3.11 (1.63-5.41) 5.28 (2.45-10.0)
Major bleeding 0 1.34 (0.49-2.98) 2.20 (0.70-5.30) 0 1.40 (0.51-3.10) 2.59 (0.82-6.25)
Overall death 7.82 (2.49-18.9) 4.53 (2.73-7.10) 13.1 (8.59-19.2) 5.37 (1.97-11.9) 7.48 (5.03-10.7) 8.35 (4.65-13.9)

Abbreviations: CAD, coronary artery disease; CVD, cerebrovascular disease; PAD, Peripherals artery disease.

therapy for 12 months in patients at high risk of bleeding [30]. In our ex- Acknowledgements
perience, the most common subsequent event among CAD patients
with AF was MI, and their incidence of stroke was similar to that of We express our gratitude to S & H Medical Science Service for their
major bleeding. The higher risk for MI than for stroke suggests that in quality control, logistic and administrative support. We thank Salvador
patients at high risk for bleeding (26% of the population according to Ortíz, Prof. Universidad Autónoma de Madrid and Statistical Advisor S &
HAS-BLED score), antiplatelet therapy should be preferred over H Medical Science Service for the statistical analysis of the data pres-
anticoagulation. ented in this paper.
Among patients with CVD, the incidence of subsequent stroke far
exceeded that of MI, and anticoagulant therapy should be the first
choice. However, since we do not exactly know how many of these Appendix A
strokes were cardio-embolic, concomitant use of antiplatelets should
be also encouraged in patients at low risk for bleeding. Finally, pa- Members of the FRENA Registry: Aguilar E, Álvarez LR, Arnedo G,
tients with PAD had a high and similar incidence of subsequent MI Coll R, García-Díaz A, Monreal M, Mujal A, Pascual MT, Piedecausa
and stroke, but they also had the highest incidence of bleeding. We M, Sahuquillo JC, Sánchez Muñoz-Torrero JF, Suriñach JM, Toril J,
suggest that these patients might benefit from antiplatelet therapy, Yeste M.
and only those with a low risk for bleeding (56% of the patients,
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