Original Paper

Med Princ Pract 2016;25:316–322 Received: August 3, 2015

Accepted: April 14, 2016
DOI: 10.1159/000446184
Published online: May 10, 2016

Nebivolol versus Carvedilol or Metoprolol in

Patients Presenting with Acute Myocardial
Infarction Complicated by Left Ventricular
Dysfunction
Mehmet Ozaydin a Habil Yucel b Sule Kocyigit c Mehmet Koray Adali d
       

Fatih Aksoy e Fatih Kahraman a Bayram Ali Uysal f Dogan Erdogan a

       

Ercan Varol a Abdullah Dogan g
   

a
Department of Cardiology, Suleyman Demirel University, Isparta, b State Hospital, Manisa, c Servergazi State
     

Hospital, Denizli, d State Hospital, Bucak, e State Hospital, Dinar, f State Hospital, Manavgat, and
     

g
Katip Celebi University, Izmir, Turkey
   

Key Words (14.5 vs. 31.5%; p = 0.03). However, event rates were similar
Beta-blockers · Myocardial infarction · Major cardiac events between the patients treated with carvedilol and those
treated with the metoprolol (20.3 vs. 31.5%, p > 0.05) and
between the patients treated with nebivolol and carvedilol
Abstract (14.5 vs. 20.3%, p > 0.05). Conclusion: The patients treated
Objective: The aim of this study was to evaluate the efficacy with nebivolol experienced 12-month cardiovascular events
of nebivolol, carvedilol or metoprolol succinate on the out- at a lower rate than those treated with metoprolol suc-
come of patients presenting with acute myocardial infarc- cinate. However, event rates were similar between the
tion (AMI) complicated by left ventricular dysfunction. Sub- carvedilol and the metoprolol succinate groups and be-
jects and Methods: Patients (n = 172, aged 28–87 years) tween the nebivolol and the carvedilol groups.
with AMI and left ventricular ejection fraction ≤0.45 were © 2016 S. Karger AG, Basel
randomized to the nebivolol (n = 55), carvedilol (n = 60) and
metoprolol succinate (n = 57) groups. Baseline demograph-
ic and clinical characteristics and composite event rates of Introduction
nonfatal MI, cardiovascular mortality, hospitalization due to
unstable angina pectoris or heart failure, stroke or revascu- Beta-blockers (BBs) decrease mortality and morbidity
larization during the 12-month follow-up were compared and improve left ventricular (LV) function in chronic
among the groups using the χ2 test, t test or log-rank test as heart failure [1–3]. They also decrease ischemic events
appropriate. Results: Baseline demographic and clinical and mortality after acute myocardial infarction (AMI)
characteristics were similar in the three groups. The com- with greater beneficial effects in those who develop LV
posite end point during follow-up was lower in the patients dysfunction and/or heart failure [1, 4]. Four BBs have
treated with nebivolol than those treated with metoprolol been shown to be effective in heart failure: metoprolol,

© 2016 S. Karger AG, Basel Dr. Mehmet Ozaydin

1011–7571/16/0254–0316$39.50/0 Suleyman Demirel University, Tip Fakultesi Hastanesi
Kardiyoloji AD, Cunur
E-Mail karger@karger.com This is an Open Access article licensed under the terms of the
TR–32200 Isparta (Turkey)
www.karger.com/mpp Creative Commons Attribution-NonCommercial 3.0 Un-
E-Mail mehmetozaydin @ hotmail.com
ported license (CC BY-NC) (www.karger.com/OA-license),
applicable to the online version of the article only. Distribu-
tion permitted for non-commercial purposes only.
 Assessed for eligibility
(n = 728)

Died (n = 2)
Not meeting inclusion criteria (n = 552)
Refused to participate (n = 2)

Randomized (n = 172)

Allocated to metoprolol Allocated to carvedilol Allocated to nebivolol

(n = 57) (n = 60) (n = 55)

In-hospital withdrawal (n = 3) In-hospital withdrawal (n = 1) In-hospital withdrawal (n = 0)

In-hospital death (n = 0) In-hospital death (n = 0) In-hospital death (n = 0)
Lost to follow-up (n = 0) Lost to follow-up (n = 0) Lost to follow-up (n = 0)

Analyzed (n = 54) Analyzed (n = 59) Analyzed (n = 55)

Fig. 1. Flow diagram of the inclusion of pa-
tients in the study.

carvedilol, bisoprolol and nebivolol. Metoprolol, biso- Subjects and Methods

prolol and nebivolol are β1-selective BBs. However,
carvedilol has β1 and β2 receptor and α1 receptor blocker This was a single-center, randomized, active-controlled and
and Μ2 receptor upregulation properties. Nebivolol has end point-blinded study. Patients with a diagnosis of AMI based
on clinical, electrocardiographic and cardiac biomarker criteria
nitric oxide-releasing and vasodilatory properties and in- [12] and an echocardiographic LV ejection fraction ≤0.45 were
hibits endothelial proliferation [5–7]. included. Transthoracic echocardiography was performed in each
A comparison of different BBs in patients with LV dys- patient before the randomization, and the echocardiographic LV
function and/or heart failure showed divergent results. ejection fraction was determined by the Simpson method [13]. A
Carvedilol showed better results on clinical end points as total of 728 patients presenting with ST elevation or non-ST eleva-
tion MI between March 2009 and March 2012 were screened. The
compared with metoprolol in patients with chronic heart inclusion criteria were patients >18 years old presenting with AMI
failure [2], but they showed similar effects on the outcomes and an ejection fraction ≤0.45. Exclusion criteria were patients
in patients with AMI complicated by LV systolic dysfunc- with an ejection fraction >0.45, Killip class IV heart failure, un-
tion [7]. A comparison of metoprolol and nebivolol showed stable angina pectoris, prior MI, previous BB or α-blocker use,
that metoprolol deteriorated LV systolic function in pa- baseline heart rate <60 bpm, second- or third-degree atrioventric-
ular block, systolic blood pressure <90 mm Hg, severe chronic ob-
tients with systolic dysfunction but not nebivolol [8]. How- structive pulmonary disease and symptomatic peripheral arterial
ever, carvedilol and nebivolol showed similar efficacy, in- disease. Based on these criteria, 552 patients were excluded: 352
cluding clinical end points in patients with systolic dys- due to ejection fraction >0.45, 133 because of previous use of BBs,
function and hypertension [9] or chronic heart failure [10]. 22 with a heart rate <60, 12 with systolic blood pressure <90 mm
In a meta-analysis [11], carvedilol was shown to reduce Hg, 4 with second- or third-degree atrioventricular block, 6 with
Killip class IV heart failure, 15 due to unstable angina pectoris, 2
all-cause mortality as compared with β1-selective BBs in- with severe chronic obstructive pulmonary disease, 4 because of
cluding metoprolol and nebivolol in randomized direct prior heart failure and 2 with previous MI. In addition, 2 patients
comparison trials in patients with heart failure. No head- died before randomization and 2 refused to participate. Therefore,
to-head comparison of nebivolol, carvedilol and metopro- 172 patients (aged 28–87 years) were included in this study (fig. 1;
lol has been conducted in ischemic LV dysfunction. There- table 1). Of the eligible patients, 57 were randomized to metopro-
lol succinate, 60 to carvedilol and 55 to nebivolol. Selection for
fore, the aim of this study was to compare nebivolol with these groups was conducted using numbers in sealed envelopes.
carvedilol or metoprolol succinate in patients presenting Three patients in the metoprolol succinate group (bronchospasm,
with AMI and an LV ejection fraction ≤0.45. n = 1; atrioventricular block, n = 2) and 1 patient in the carvedilol

Myocardial Infarction and Major Cardiac Med Princ Pract 2016;25:316–322 317
Events DOI: 10.1159/000446184
Table 1. Baseline characteristics

Characteristics Metoprolol succinate Carvedilol Nebivolol p

(n = 57) (n = 60) (n = 55)

Age, years 59 ± 13 59 ± 12 61 ± 11 0.98

Male gender 48 (84.2) 47 (78.3) 50 (90.9) 0.18
Smoking 33 (57.9) 38 (63.3) 28 (50.9) 0.29
Hypertension 21 (36.8) 16 (26.7) 17 (30.9) 0.48
Diabetes mellitus 9 (15.8) 11 (18.3) 8 (14.5) 0.91
Non-ST elevation MI 2 (3.5) 2 (3.3) 5 (9.1) 0.80
ST elevation MI 55 (96.5) 58 (96.7) 52 (90.9) 0.72
Anterior 44 (77.2) 47 (78.3) 36 (65.4) 0.50
Nonanterior 11 (19.3) 11 (18.3) 14 (25.5) 0.30
Killip class
Class I 43 (75.4) 44 (73.3) 41 (74.5) 0.80
Class II 11 (19.3) 12 (20) 10 (18.2)
Class III 3 (5.3) 4 (6.7) 4 (7.3)
Creatinine, mg/dl 1.1 ± 0.4 1.07 ± 0.3 1.03 ± 0.1 0.50
Total cholesterol, mg/dl 178 ± 36 161 ± 34 173 ± 36 0.62
Triglyceride, mg/dl 123 ± 52 123 ± 48 127 ± 70 0.97
HDL cholesterol, mg/dl 41 ± 9 41 ± 6 41 ± 9 0.97
LDL cholesterol, mg/dl 108 ± 42 95 ± 27 111 ± 24 0.37
Ejection fraction, % 35 (20 – 45) 35 (25 – 45) 35 (30 – 45) 0.54
Baseline systolic BP, mm Hg 130 (90 – 150) 120 (80 – 200) 135 (90 – 180) 0.26
Baseline diastolic BP, mm Hg 80 (60 – 100) 75 (50 – 120) 80 (55 – 100) 0.28
Baseline heart rate, beats/min 75 (61 – 110) 80 (60 – 120) 76 (60 – 120) 0.43
Peak CK-MB 100 (41 – 520) 111 (26 – 573) 143 (45 – 380) 0.30
Medications before hospitalization
ACEI and/or ARB 8 (14) 7 (11.7) 7 (12.7) 0.92
Acetyl salicylic acid 4 (7) 6 (10) 4 (7.3) 0.84
Statins 6 (10.5) 7 (11.7) 5 (9.1) 0.95
Oral antidiabetics 5 (8.8) 5 (8.3) 2 (3.6) 0.46
Insulin 2 (3.5) 1 (1.7) 1 (1.8) 0.75
Thiazide diuretics 3 (5.3) 2 (3.3) 1 (1.8) 0.58
Medications started during hospitalization
ACEI and/or ARB 56 (98.2) 58 (96.7) 54 (98.2) 0.80
Spironolactone 26 (45.6) 30 (50) 22 (40) 0.45
Statin 54 (94.8) 55 (82) 50 (90.9) 0.58
Acetyl salicylic acid 51 (89.5) 56 (93.3) 52 (94.5) 0.54
Clopidogrel 54 (93.1) 61 (100) 54 (98.2) 0.90
Recanalization in ST segment elevation MI 0.48
Thrombolytic 22 (40.1) 23 (39.7) 21 (38.1)
Streptokinase 8 (14.5) 10 (17.2) 9 (16.4)
t-PA 14 (25.6) 13 (22.5) 13 (23.6)
Primary PCI 21 (38.1) 21 (36.2) 19 (34.5)
No recanalization 12 (21.8) 14 (24.1) 11 (20) 0.68
Rescue PCI 7 (12.2) 8 (13.3) 6 (10.9) 0.74
Treatment during index event 0.76
Medical treatment 14 (24.2) 15 (24.6) 13 (23.6)
PCI 31 (53.4) 35 (57.4) 35 (63.6)
CABG 13 (22.4) 11 (18) 7 (12.7)
Implantable cardioverter defibrillator implantation
(for primary prevention) 2 (3.5) 3 (5.0) 2 (3.6) 0.90

Data are presented as the mean ± SD, median (range) or n (%).

HDL = High-density lipoprotein; LDL = low-density lipoprotein; CK-MB = creatine kinase myocardial band; BP = blood pressure;
ACEI = angiotensin-converting enzyme inhibitor; ARB = angiotensin receptor blocker: t-PA = tissue plasminogen activators; CABG =
coronary artery bypass surgery.

318 Med Princ Pract 2016;25:316–322 Ozaydin/Yucel/Kocyigit/Adali/Aksoy/

DOI: 10.1159/000446184 Kahraman/Uysal/Erdogan/Varol/Dogan
Table 2. Follow-up findings

Characteristics Metoprolol Carvedilol Nebivolol p1 p2 p3 p4

succinate overall neb vs. met neb vs. car car vs. met

Tolerability
n 57 60 55
BB withdrawal 3 (5.3) 1 (1.7) 0
The reason for withdrawal
Bronchospasm 1 (1.8) 0 0
Second-/third-degree
atrioventricular block 2 (3.5) 1 (1.7) 0
12-month follow-up
n 54 59 55
Primary composite end pointa 17 (31.5) 12 (20.3) 8 (14.5) 0.03 0.03 0.46 0.20
Mortality 1 (1.9) 1 (1.7) 2 (3.6) 0.78
Nonfatal MI 2 (3.7) 3 (5.1) 1 (1.8) 0.60
Hospitalizationb 12 (22.2) 8 (13.6) 7 (12.7) 0.32
Revascularization 2 (3.7) 0 1 (1.8) 0.33
Stroke 2 (3.5) 0 1 (1.8) 0.33

met = Metoprolol; car = carvedilol; neb = nebivolol.

a Cardiovascular mortality, hospitalization due to unstable angina pectoris or heart failure, revascularization, nonfatal MI or stroke.
b Hospitalization due to unstable angina pectoris or heart failure.

group (atrioventricular block, n = 1) were withdrawn from therapy synchronization therapy was heart failure and QRS duration >120
(table 2). Therefore, 12-month follow-up was available for 168 pa- ms with a left bundle branch block pattern. However, as this crite-
tients (nebivolol, n = 55; carvedilol, n = 59; metoprolol succinate, rion was not met, this therapy was not required in any patient. The
n = 54). study complies with the Declaration of Helsinki of 1975, as revised
The BBs were started within the first 3 days after the onset of in 1983. The Institutional Review Board approved the study and
symptoms. Metoprolol, carvedilol and nebivolol were started at written informed consent was obtained from all of the subjects.
doses of 25 mg once daily, 3.125 mg twice daily and 1.25 mg once The primary end point was the composite of nonfatal MI, cardio-
daily, respectively. The dose was titrated up to a tolerable dose. In vascular mortality, hospitalization due to unstable angina pectoris
cases where the lowest dose was not tolerated, the study drug was or heart failure, stroke and revascularization during the 12 months
stopped. Blood pressure and heart rate were checked every day of follow-up. Patients were seen every week for the first month and
and, depending on the patient’s hemodynamic status, the meto- at 3-month intervals thereafter for the assessment of end points
prolol dose was increased gradually to 50, 100 and 200 mg once and tolerability of the study drugs.
daily, carvedilol was increased to 6.25, 12.5 and 25 mg twice daily,
and nebivolol was increased to 2.5, 5 and 10 mg once daily. It was Statistical Analysis
intended that the target dose would be reached within 1 month The Kolmogorov-Smirnov test was used for the distribution of
(200 mg once daily, 25 mg twice daily and 10 mg once daily for numeric variables and factors with a normal distribution are ex-
metoprolol, carvedilol and nebivolol, respectively). The patients pressed as the mean ± SD and were compared with analysis of vari-
were treated according to the most recent guidelines [14, 15]. Re- ance (ANOVA), which was used to compare age, creatinine levels
canalization with either primary percutaneous coronary interven- and lipid parameters. Variables without a normal distribution
tion (PCI) or thrombolytic treatment was performed in patients were expressed as the median (range) and were compared using
with ST elevation MI presenting within 12 h from the onset of the the Kruskal-Wallis test for systolic and diastolic blood pressures,
symptoms. Patients were taken to rescue PCI if no recanalization heart rate, peak creatine kinase myocardial band, and ejection frac-
occurred at 1 h of thrombolytic treatment. If there was no contra- tion. Categorical variables are expressed as numbers and percent-
indication, all patients received angiotensin-converting enzyme ages. Continuous variables were compared using one-way ANO-
inhibitor or angiotensin receptor blocker, acetyl salicylic acid, VA or the Kruskal-Wallis test, and categorical variables were com-
clopidogrel, statins and low-molecular-weight heparin. All the pa- pared using χ2 or Fisher’s exact test as appropriate. Post hoc
tients without contraindications underwent coronary angiogra- analyses were performed using the Scheffé correction test for con-
phy (Schimatzu, Kyoto, Japan) by a femoral arterial approach trolling type 1 error if the overall test was significant. Post hoc
within 24 h of the presentation. An implantable cardioverter defi- analyses were not performed if the overall test did not reach a sig-
brillator was implanted for primary prevention in patients with an nificant difference. The Kaplan-Meier method with the log-rank
ejection fraction <30% and NYHA functional class II or III symp- test was used to compare the probability of freedom from com-
toms occurring ≥40 days post-MI. The indication for cardiac re- bined composite end points. Composite end point event rates were

Myocardial Infarction and Major Cardiac Med Princ Pract 2016;25:316–322 319
Events DOI: 10.1159/000446184
 carvedilol and metoprolol succinate groups, and between
1.0 the nebivolol and the carvedilol groups during the
Nebivolol 12-month follow-up period (both log-rank p > 0.05;
0.8 Carvedilol fig.  2). The mean daily doses reached for metoprolol,
Metoprolol carvedilol and nebivolol were 57 ± 27 mg once a day,
Event-free survival (%)

0.6
10 ± 3 mg twice a day and 5.5 ± 2 mg once a day, respec-
tively.
0.4 log-rank
p = 0.03 (metoprolol vs. nebivolol)
p = 0.19 (metoprolol vs. carvedilol) Discussion
p = 0.40 (carvedilol vs. nebivolol)
0.2
In this study, patients with AMI and LV ejection frac-
0 tion ≤45% treated with nebivolol experienced 12-month
0 100 200 300 400 cardiovascular events at a lower rate than those treated
Follow-up (days) with metoprolol. However, event rates were similar be-
tween the carvedilol and the metoprolol groups and be-
tween the nebivolol and the carvedilol groups. It was
Fig. 2. Freedom from primary composite end points during the
12-month follow-up period. shown in a previous study [8] that metoprolol but not
nebivolol decreased cardiac output and increased system-
ic vascular resistance and pulmonary capillary wedge
pressure in patients with systolic dysfunction. Similarly,
assumed to be 30% in the metoprolol group, 15% in the carvedilol nebivolol but not metoprolol inhibited cardiac NADPH
group and 7% in the nebivolol group [7–10, 16–19], and were com-
pared among the metoprolol, carvedilol and nebivolol groups. oxidase activation and improved LV dysfunction, and
Given the fact that patients with coronary artery disease presenting nebivolol had a significantly more pronounced inhibitory
with AMI were included in this study, we hypothesized that effect than metoprolol on cardiomyocyte hypertrophy af-
nebivolol would have the lowest event rates because it has nitric ter MI [20]. Nebivolol was also found to be superior to
oxide-releasing and antiatherosclerotic properties. With this hy- atenolol in improving diastolic functions and the maxi-
pothesis, 47 patients in each group were required to detect signifi-
cance with an alpha level of 0.05, and a power of 0.80. Analysis was mal exercise duration of patients with ischemic LV dys-
performed on the intention-to-treat rule. A p value <0.05 was con- function [21]. However, in patients with nonischemic
sidered significant. SPSS 15 (SPSS Inc., Chicago, Ill., USA) was heart failure, both nebivolol and carvedilol improved LV
used for the analysis. diastolic functions and also performed similarly on fol-
low-up [22]. On the other hand, a recent study showed
that lung diffusion and exercise performance were higher
Results with nebivolol than carvedilol, but carvedilol allowed bet-
ter ventilation efficiency than nebivolol during exercise
Baseline findings were similar among the groups (all p [23]. Although previous studies indicated the superiority
values >0.05; table 1). The composite end point of nonfa- of nebivolol over metoprolol, the present study is the first
tal MI, cardiovascular mortality, hospitalization due to that shows lower long-term event rates with nebivolol
unstable angina pectoris or heart failure, stroke or revas- than metoprolol in patients with AMI complicated by LV
cularization during the 12-month follow-up period was dysfunction. However, nebivolol and carvedilol, which
lower in the nebivolol group (n = 8, 14.5%) than the meto- had not been compared in this study population previ-
prolol succinate group (n = 17, 31.5%; p = 0.03). How- ously, had similar event rates in the present study. Nebivo-
ever, event rates were similar between the carvedilol and lol plays an important role in patients with reduced endo-
the metoprolol succinate groups and between the nebivo- thelial dysfunction, especially for those who have AMI, as
lol and the carvedilol groups (n = 12, 20.3%, vs. n = 17, it has nitric oxide-induced vasodilatory properties and
31.5%; n = 8, 14.5%, vs. n = 12, 20.3%, respectively; both may offer antiatherosclerotic activity by its inhibitory ef-
p > 0.05). The Kaplan-Meier survival analysis showed fects on oxidative stress and vascular smooth muscle pro-
that freedom from composite end points was higher in liferation [24]. By its vasodilatory effects, nebivolol de-
the nebivolol group than in the metoprolol succinate creases peripheral vascular resistance and increases stroke
group (log-rank p = 0.03), but was similar between the volume, which is very beneficial in heart failure [5].

320 Med Princ Pract 2016;25:316–322 Ozaydin/Yucel/Kocyigit/Adali/Aksoy/

DOI: 10.1159/000446184 Kahraman/Uysal/Erdogan/Varol/Dogan
Carvedilol has been found to have better results than oth- tings showed that the benefits of BBs are mainly due to a
er BBs in animal models of MI [25] and in decreasing class effect with no superiority of any BB over the others
cardiovascular event rates and increasing ejection frac- [29]. Moreover, beneficial effects of BBs could mainly be
tion in patients with heart failure [26]. Similarly, a recent related to the degree of the heart rate reduction achieved,
meta-analysis [11] indicated that carvedilol reduced all- which is more successfully achieved with the use of β1-
cause mortality as compared with atenolol, bisoprolol, selective BBs such as nebivolol or metoprolol [16]. In ad-
metoprolol and nebivolol in randomized direct compari- dition, β1-receptor stimulation increases myocyte apop-
son heart failure trials. On the other hand, carvedilol and tosis, but β2-receptor stimulation has an opposite effect
nebivolol showed no superiority over one another, in- on apoptosis [30]. All of these mechanisms could explain
cluding clinical end points in patients with systolic dys- why carvedilol was not superior to nebivolol or metopro-
function and hypertension [9, 10]. In AMI patients with lol in AMI patients. In addition, both the COMET and
an LV ejection fraction <0.45, carvedilol and metoprolol CAPRICORN studies, which showed a superiority of
showed similar long-term clinical end points, but the carvedilol over metoprolol or placebo, included patients
safety profile and quality of life were better with carvedilol with clinical heart failure, which was not a required inclu-
[7]. In addition, carvedilol and metoprolol exhibited sim- sion criterion in the present study or in other studies in-
ilar short-term clinical end points, reperfusion arrhyth- cluding AMI patients [7, 16, 17]. We speculate that
mias, cardiac and neurohumoral markers and LV ejec- carvedilol may not be as beneficial in AMI patients as it is
tion fraction in patients undergoing primary PCI [16]. in those with chronic heart failure. The limitation of this
The long-term clinical end point rates of AMI patients study was a highly selected cohort group without any con-
with a mean ejection fraction of 0.55 were also not statis- trols due to ethical considerations.
tically different between the carvedilol and atenolol
groups [17]. The present study is in line with previous
studies that show similar event rates with nebivolol and Conclusion
carvedilol. Carvedilol has antioxidant, anti-inflammato-
ry, antiarrhythmic, vasodilatory and β1, β2 and α1-receptor The nebivolol group experienced 12-month cardio-
blocker properties [11, 18, 19]. Its β2 receptor blocker and vascular events at a lower rate than the metoprolol suc-
antioxidant effects are critical as β2 receptors [6] and oxi- cinate group. The difference in event rates was mainly
dative stress [27] are increased in heart failure. Previous due to greater rehospitalization in the metoprolol group.
experimental and clinical heart failure studies indicated However, event rates were similar between the carvedilol
the superiority of carvedilol over other BBs and its effec- and the metoprolol groups and between the nebivolol and
tiveness in heart failure with preserved LV ejection frac- the carvedilol groups. Withdrawal rates were statistically
tion [28]. However, direct comparison studies in the AMI similar among the three groups. If confirmed by a larger
settings and a new meta-analysis in the heart failure set- study, this would be a clinically important finding.

References
1 The MERIT-HF Study Group: Effect of meto- 4 The CAPRICORN Investigators: Effect of 7 Mrdovic IB, Savic LZ, Perunicic JP, et al: Ran-
prolol CR/XL in chronic heart failure: Meto- carvedilol on outcome after myocardial in- domized active controlled study comparing
prolol CR/XL Randomised Intervention Trial farction in patients with left-ventricular dys- effects of treatment with carvedilol versus
in Congestive Heart Failure (MERIT-HF). function: the CAPRICORN randomized trial. metoprolol in patients with left ventricular
Lancet 1999;353:2001–2007. Lancet 2001;357:1385–1390. dysfunction after acute myocardial infarc-
2 Poole-Wilson PA, Swedberg K, Cleland JG, et 5 DiNicolantonio JJ, Fares H, Niazi AK, et al: tion. Am Heart J 2007;154:116–122.
al: Comparison of carvedilol and metoprolol β-Blockers in hypertension, diabetes, heart 8 Triposkiadis F, Giamouzis G, Kelepeshis G, et
on clinical outcomes in patients with chronic failure and acute myocardial infarction: a re- al: Acute hemodynamic effects of moderate
heart failure in the Carvedilol or Metoprolol view of the literature. Open Heart 2015; doses of nebivolol versus metoprolol in pa-
European Trial (COMET): randomised con- 2:e000230. tients with systolic heart failure. Int J Clin
trolled trial. Lancet 2003;362:7–13. 6 Ripley TL, Saseen JJ: β-Blockers: a review of Pharmacol Ther 2007;45:71–77.
3 The SENIORS Investigators: Randomized tri- their pharmacological and physiological di- 9 Marazzi G, Volterrani M, Caminiti G, et al:
al to determine the effect of nebivolol on mor- versity in hypertension. Ann Pharmacother Comparative long term effects of nebivolol
tality and cardiovascular hospital admission 2014:48;723–733. and carvedilol in hypertensive heart failure
in elderly patients with heart failure. Eur patients. J Card Fail 2011;17:703–709.
Heart J 2005;26:215–225.

Myocardial Infarction and Major Cardiac Med Princ Pract 2016;25:316–322 321
Events DOI: 10.1159/000446184
10 Lombardo RM, Reina C, Abrignani MG, et al: mary coronary intervention – the PASSAT in patients with non-ischemic heart failure.
Effects of nebivolol versus carvedilol on left study. Clin Res Cardiol 2006;95:31–41. Cardiol J 2014;21:76–82.
ventricular function in patients with chronic 17 Jonsson G, Abdelnoor M, Muller C, et al: A 23 Contini M, Apostolo A, Cattadori G: Multi-
heart failure and reduced left ventricular sys- comparison of the two beta-blockers parametric comparison of carvedilol, vs.
tolic function. Am J Cardiovasc Drugs 2006; carvedilol and atenolol on left ventricular nebivolol, vs. bisoprolol in moderate heart
6:259–263. ejection fraction and clinical end-points after failure: the CARNEBI trial. Int J Cardiol 2013;
11 DiNicolantonio JJ, Lavie CJ, Fares H, et al: myocardial infarction: a single-centre, ran- 168:2134–2140.
Meta-analysis of carvedilol versus beta 1 se- domized study of 232 patients. Cardiology 24 Weiss R: Nebivolol: a novel beta-blocker with
lective beta-blockers (atenolol, bisoprolol, 2005;103:148–155. nitric oxide-induced vasodilatation. Vasc
metoprolol, and nebivolol). Am J Cardiol 18 McMurray J, Køber L, Robertson M, et al: An- Health Risk Manag 2006;2:303–308.
2013;111:765–769. tiarrhythmic effect of carvedilol after acute 25 Wei S, Chow LTC, Sanderson JE: Effect of
12 Thygesen K, Alpert JS, White HD, et al: Uni- myocardial infarction: results of the Carvedilol carvedilol in comparison with metoprolol on
versal definition of myocardial infarction. Post-Infarct Survival Control in Left Ventric- myocardial collagen postinfarction. J Am Coll
Circulation 2007;116:2634–2653. ular Dysfunction (CAPRICORN) trial. J Am Cardiol 2000;36:276–281.
13 Grossgasteiger M, Hien MD, Graser B, et al: Coll Cardiol 2005;45:525–530. 26 Packer M, Antonopoulos GV, Berlin JA, et al:
Image quality influences the assessment of left 19 Torp-Pedersen C, Poole-Wilson PA, Swed- Comparative effects of carvedilol and meto-
ventricular function: an intraoperative com- berg K, et al: Effects of metoprolol and prolol on left ventricular ejection fraction in
parison of five 2-dimensional echocardio- carvedilol on cause specific mortality and heart failure: results of a meta-analysis. Am
graphic methods with real-time 3-dimension- morbidity in patients with chronic heart fail- Heart J 2001;141:899–907.
al echocardiography as a reference. J Ultra- ure – COMET. Am Heart J 2005; 149: 370– 27 Karabacak M, Dogan A, Tayyar S, et al: Oxi-
sound Med 2014;33:297–306. 376. dative stress status increase in patients with
14 Steg PG, James SK, Atar D, et al: ESC guide- 20 Sorrentino SA, Doerries C, Manes C, et al: nonischemic heart failure. Med Princ Pract
lines for the management of acute myocardial Nebivolol exerts beneficial effects on endothe- 2014;23:532–537.
infarction in patients presenting with ST-seg- lial function, early endothelial progenitor 28 Yamamoto K, Origasa H, Suzuki Y, et al: Rela-
ment elevation. Eur Heart J 2012; 33: 2569– cells, myocardial neovascularization, and left tion of risk factors with response to carvedilol
2619. ventricular dysfunction early after myocardial in heart failure with preserved ejection frac-
15 Masoudi FA, Bonow RO, Brindis RG, et al: infarction beyond conventional β1-blockade. J tion – a report from the Japanese Diastolic
ACC/AHA 2008 statement on performance Am Coll Cardiol 2011;57:601–611. Heart Failure Study (J-DHF). J Cardiol 2013;
measurement and reperfusion therapy: a re- 21 Rousseau MF, Chapelle F, van Eyll C, et al: 63:424–443.
port of the ACC/AHA Task Force on Perfor- Medium-term effects of beta-blockade on left 29 Chatterjee S, Biondi-Zoccai G, Abbate A:
mance Measures (work group to address the ventricular mechanics: a double-blind, place- Benefits of β blockers in patients with heart
challenges of performance measurement and bo-controlled comparison of nebivolol and failure and reduced ejection fraction: network
reperfusion therapy). J Am Coll Cardiol 2008; atenolol in patients with ischemic left ventric- meta-analysis. BMJ 2013;346:f55.
52:2100–2112. ular dysfunction. J Card Fail 1996;2:15–23. 30 Communal C, Singh K, Sawyer DB, et al: Op-
16 Tölg R, Witt M, Schwarz B, et al: Comparison 22 Dogan A, Karabacak M, Tayyar S, et al: Com- posing effects of 1- and 2-adrenergic recep-
of carvedilol and metoprolol in patients with parison of the effects of carvedilol and nebivo- tors on cardiac myocyte apoptosis. Circula-
acute myocardial infarction undergoing pri- lol on diastolic functions of the left ventricle tion 1999;100:2210–2222.

322 Med Princ Pract 2016;25:316–322 Ozaydin/Yucel/Kocyigit/Adali/Aksoy/

DOI: 10.1159/000446184 Kahraman/Uysal/Erdogan/Varol/Dogan