Вы находитесь на странице: 1из 5

Meta-Analysis of Carvedilol Versus Beta 1 Selective Beta-Blockers

(Atenolol, Bisoprolol, Metoprolol, and Nebivolol)


James J. DiNicolantonio, PharmDa,*, Carl J. Lavie, MDb,c, Hassan Fares, MDb, Arthur R. Menezes, MDb,
and James H. OKeefe, MDd

Because carvedilol is a unique vasodilating b blocker (BB) exerting antioxidant activity and
pleiotropic effects, it was theorized that it may confer more potent benecial effects on
cardiovascular mortality and morbidity in acute myocardial infarction (AMI) and heart
failure (HF) settings. A systematic review and meta-analysis was performed of randomized,
controlled, direct-comparison trials that included adults receiving atenolol, bisoprolol,
metoprolol, nebivolol, or carvedilol to evaluate the effects of carvedilol compared to other
BBs on mortality, cardiovascular events, and hospital readmissions in the setting of AMI or
systolic HF. Compared to b1-selective BBs used in HF (8 trials, n [ 4,563), carvedilol
signicantly reduced all-cause mortality (risk ratio 0.85, 95% condence interval 0.78 to
0.93, p [ 0.0006). In 3 trials of patients with AMI (n [ 644), carvedilol signicantly
reduced all-cause mortality by 45% (xed-effects model: risk ratio 0.55, 95% condence
interval 0.32 to 0.94, p [ 0.03, random-effects model: risk ratio 0.56, 95% condence
interval 0.26 to 1.12, p = 0.10), with no reduction in non-fatal MI (risk ratio 0.61, 95%
condence interval 0.31 to 1.22, p [ 0.16). In conclusion, carvedilol, as compared against
atenolol, bisoprolol, metoprolol and nebivolol in randomized direct comparison trials,
signicantly reduced all-cause mortality in systolic HF patients. Additionally, carvedilol
signicantly reduced all-cause mortality compared with b1-selective BBs in AMI patients
using the xed-effects model but not using the random-effects model. 2013 Elsevier Inc.
All rights reserved. (Am J Cardiol 2013;111:765e769)

Although guidelines for the treatment of patients with systematic reviews of intervention studies was performed.4
acute coronary syndromes, acute myocardial infarctions Studies were identied through searches of the following
(AMIs), and heart failure (HF) recommend the use of sources: Ovid MEDLINE (1977 to 2012), PubMed (1978 to
b blockers (BBs) as rst-line therapy, they do not speci- 2011), and Embase (1977 to 2012). To identify further
cally recommend 1 BB over another.1,2 However, carvedilol potentially relevant studies missed by the electronic data-
has been shown to signicantly reduce all-cause mortality base search, reference lists from identied trials and review
and cardiovascular (CV) events (nonfatal and fatal stroke reports were manually screened. Searches were restricted to
and myocardial infarction [MI]) compared to metoprolol in
patients with HF (in the Carvedilol or Metoprolol European
Trial [COMET]).3 Thus, we sought to compare carvedilol
against the most frequently prescribed b1-selective BBs
(atenolol, metoprolol, and bisoprolol) and the most recently
approved b1-selective BB (nebivolol) in patients with AMI
or systolic HF.

Methods
A systematic review of the available published research
according to the Preferred Reporting Items for Systematic
Reviews and Meta-Analyses guidelines for the conduct of

a
Wegmans Pharmacy, Ithaca, New York; bJohn Ochsner Heart and
Vascular Institute, Ochsner Clinical School, The University of Queensland
School of Medicine, New Orleans, Louisiana; cPennington Biomedical
Research Center, Baton Rouge, Louisiana; and dMid America Heart Insti-
tute at Saint Lukes Hospital, University of MissourieKansas City, Kansas
City, Missouri. Manuscript received November 2, 2012; revised manuscript
received and accepted November 12, 2012.
See page 768 for disclosure information.
*Corresponding author: Tel: 607-277-5750; fax: 607-277-5890.
E-mail address: jjdinicol@gmail.com (J.J. DiNicolantonio). Figure 1. Process for selecting included trials.

0002-9149/13/$ - see front matter 2013 Elsevier Inc. All rights reserved. www.ajconline.org
http://dx.doi.org/10.1016/j.amjcard.2012.11.031

Downloaded from ClinicalKey.com at Amarillo VAMC Health Care System November 20, 2016.
For personal use only. No other uses without permission. Copyright 2016. Elsevier Inc. All rights reserved.
766 The American Journal of Cardiology (www.ajconline.org)

Figure 2. Forest plot of relative risk for all-cause mortality in patients with HF.

the English language and were updated using automated heterogeneity, and I2 >50% denotes substantial heteroge-
weekly e-mail alerts until August 2012. Full details of the neity.7 Two-tailed p values <0.05 were considered statisti-
search strategies and excluded trials are available as cally signicant for all analyses. Cochrane Review Manager
appendices by request. version 5 software was used for all analyses. A sensitivity
Studies were selected for inclusion on the basis of the analysis was conducted to account for different BBs in the
following criteria: (1) study design: randomized controlled direct-comparison trials against carvedilol.
trials, (2) type of participants: adults (aged 18 years), (3)
intervention: carvedilol, (4) comparator: atenolol, bisopro-
Results
lol, metoprolol, or nebivolol, and (5) outcomes: all-cause
mortality, CV events (fatal and nonfatal strokes, fatal and The search of the published research yielded 1,105 titles, of
nonfatal MI), and HF or CV-related hospital readmissions. which 40 were reviewed in full text on the basis of the
We excluded studies that did not report mortality or inclusion criteria (Figure 1). Of these, 11 studies were deemed
morbidity outcomes. The titles and abstracts of studies eligible for inclusion (Figure 1).3,8e17 Tables containing the
identied by the search strategy were independently characteristics of the included studies are available by request.
screened by 2 reviewers (J.J.D. and H.F.), and clearly All trials were randomized direct comparison trials
irrelevant studies were discarded. against carvedilol in patients with either HF or AMI. All
The following data elements were extracted from each background medications and baseline characteristics were
study: the number of patients per arm, the nature of the statistically similar between the comparison groups in each
intervention, patient inclusion criteria, cause of HF, type of trial, except for 3 trials: Mrdovic et al8 had signicantly
AMI index event (i.e. percentage noneST-segment eleva- more patients with hyperlipidemia at baseline in the carve-
tion MI, percentage ST-segment elevation MI, percentage dilol group and older, more Killip class IV HF patients in
unstable angina), and baseline and follow-up blood pres- the metoprolol group; Jonsson et al9 had signicantly more
sure, ejection fraction, and heart rate (supplemental tables atenolol patients being female and receiving intravenous
are available by request). The following outcomes were also diuretics during treatment; and Marazzi et al10 had signi-
extracted from each trial: all-cause mortality, CV events cantly more baseline coronary artery disease or idiopathic
(nonfatal and fatal stroke, nonfatal and fatal MI), and HF or dilated cardiomyopathy patients and higher baseline heart
CV-related hospital readmissions. Quality assessment was rates in the carvedilol group but higher baseline systolic
judged according to the following criteria: concealment of blood pressures and lower ejection fractions in the nebivolol
treatment allocation; similarity of the 2 groups at baseline group. Trials enrolled a median of 150 patients (interquartile
regarding prognostic factors and medication use; blinding of range 67 to 3.029) with a median follow-up period of
outcome assessors, care providers, and patients; complete- 12 months (interquartile range 0.5 to 58).
ness of follow-up; and intention-to-treat analysis (supple- Four studies scored well on the methodologic quality
mental tables are available by request). Overall study quality indicators (supplemental tables with details are available by
was quantied using the Jadad score.5 The data extraction request). Concealed allocation and blinding of 1 outcome
and quality assessment was undertaken using a standardized assessment were stated in 3 and 5 of 11 trials, respectively.
pro forma by 2 reviewers (H.F. and A.R.M.). Eight trials (n 4,563) reported on all-cause mortality in
We express outcome results for each study as risk ratios patients with systolic HF. There was a signicant decrease
(RRs) with 95% condence intervals (CIs). Summary esti- in mortality for carvedilol compared to b1-selective BBs
mates were computed using a DerSimonian and Laird xed (RR 0.85, 95% CI 0.78 to 0.93, p 0.0006, I2 0%;
and random-effects and xed-effects meta-analysis model. Figure 2). The number needed to treat over the course of the
We report pooled results as RRs and numbers needed to trials was 22 (95% CI 14 to 52).
treat. Statistical heterogeneity across trials was estimated Three trials (n 644) reported on all-cause mortality in
using the I2 statistic,6 where I2 <30% denotes low hetero- patients with AMI. There was a signicant 45% reduction in
geneity, I2 30% to 50% represents moderate all-cause mortality in patients on carvedilol vs. b1-selective

Downloaded from ClinicalKey.com at Amarillo VAMC Health Care System November 20, 2016.
For personal use only. No other uses without permission. Copyright 2016. Elsevier Inc. All rights reserved.
Review/Carvedilol Versus b1 b Blockers 767

Figure 3. Forest plot of relative risk for all-cause mortality in patients with AMIs.

Figure 4. Forest plot of relative risk for nonfatal MI in patients with AMIs.

Figure 5. Forest plot of relative risk for HF readmissions in patients with HF.

BBs by using a xed-effects model (RR 0.55, 95% CI 0.32 to Four HF trials compared metoprolol tartrate to carvedilol
0.94, p 0.03, Figure 3) but not by random-effects model (RR (n 3,376). Compared to metoprolol, carvedilol caused
0.56, 95% CI 0.26 to 1.12, p 0.10), I2 10%. The number a signicant reduction in all-cause mortality (RR 0.86, 95% CI
needed to treat over the course of the trials was 21 (95% CI 11 0.78 to 0.94, p 0.001, I2 0%). In the AMI setting, 2 direct-
to 227). comparison trials (n 390) indicated no signicant reduction
Three trials (n 644) reported on nonfatal MI. For in all-cause mortality with carvedilol compared to metoprolol
patients taking carvedilol compared to b1-selective BBs, tartrate (RR 0.95, 95% CI 0.13 to 7.13, I2 53%). However,
there was no reduction in nonfatal MI (RR 0.61, 95% CI the study by Mrdovic et al,8 carrying approximately 86% of
0.31 to 1.22, p 0.16, I2 0%; Figure 4). the weight for AMI mortality end points, indicated that car-
Two trials (n 3,099) reported on HF readmissions. vedilol was associated with a signicant 47% reduction in
Compared to b1-selective BBs, there was no signicant all-cause mortality (RR 0.53, 95% CI 0.29 to 0.94, p 0.02).
benet on reducing HF readmissions with carvedilol Two HF trials compared nebivolol to carvedilol (n
(RR 0.98, 95% CI 0.93 to 1.03, p 0.45) I2 0%; (Figure 5). 230). Compared to nebivolol, carvedilol was not associated
Only 1 trial (n 232) compared atenolol to carvedilol in with a reduction in all-cause mortality (RR 0.80, 95% CI
patients with AMI.9 Compared to atenolol, carvedilol did 0.22 to 2.91, p 0.73, I2 0%).10,17
not reduce all-cause mortality, although the small sample
size may have rendered this nonsignicant (RR 0.39, 95%
Discussion
CI 0.08 to 1.95, p 0.25).
Two trials in patients with HF (n 957) were performed In this systematic review of 11 randomized controlled
with bisoprolol versus carvedilol. Compared to bisoprolol, trials in 5,207 patients, we found that carvedilol signicantly
carvedilol did not reduce all-cause mortality (RR 0.54, 95% reduced all-cause mortality in patients with HF. Addition-
CI 0.22 to 1.34, p 0.19, I2 0%).11,12 ally, in patients with AMI, carvedilol signicantly reduced

Downloaded from ClinicalKey.com at Amarillo VAMC Health Care System November 20, 2016.
For personal use only. No other uses without permission. Copyright 2016. Elsevier Inc. All rights reserved.
768 The American Journal of Cardiology (www.ajconline.org)

all-cause mortality by xed-effects model (but not by Furthermore, b1-selective BBs upregulate b1 receptor
random-effects model) but did not reduce nonfatal MI density and increase b1 receptor sensitivity to adrenergic
compared to other commonly prescribed BBs, although stimulation; this has not been seen with carvedilol.22
carvedilol did demonstrate trends for reducing this end Missing doses of b1-selective BBs has been associated with
point. The preferential reduction in mortality with carvedilol a signicant increase in death (due to sudden cardiac death
in HF, however, was not associated with a signicant and HF), which may be caused by rebound tachycardia,
reduction in HF hospital readmission compared to the other leading to deterioration in patients with HF.27
BBs, suggesting a discordant relative effect of these agents In summary, improvements in ejection fraction, symp-
on mortality versus overall cardiac compensation. tomatic functional class, stroke volume, stroke work, cardiac
The potential mechanisms responsible for the observed output, insulin sensitivity, and adrenergic activity with car-
benecial impact of carvedilol compared to other BBs may in vedilol, along with a potential increase in the risk for death
part be established through carvedilols pleiotropic effects with b1-selective BBs if strict compliance is not followed,
(antioxidant and vasodilating), which are not shared by the all may contribute to the overall morbidity and mortality
commonly prescribed b1-selective BBs (i.e., atenolol, meto- benets noted with carvedilol compared to b1-selective BBs.
prolol, and bisoprolol). Compared to metoprolol, carvedilol has These ndings suggest that carvedilol reduces all-cause
been shown in 2 randomized, direct-comparison trials to mortality compared to b1-selective BBs in systolic HF patients
signicantly reduce atrial brillation after coronary artery and in patients with AMIs. Although current guidelines for the
bypass graft surgery.18,19 Moreover, in the Carvedilol Post treatment of patients with HF and acute coronary syndromes
Infarction Survival Control in Left Ventricular Dysfunction or AMIs do not recommend 1 BB over another,1,2 substantial
(CAPRICORN) trial, carvedilol caused a 76% reduction in evidence, discussed previously, appears to favor carvedilol in
arrhythmias (ventricular tachycardia, brillation, or utter; the settings of ischemic heart disease, particularly systolic HF.
p <0.0001), a 52% reduction in supraventricular arrhythmias Although a large, randomized, multicenter trial is required to
(p 0.0015), and a 26% reduction in sudden cardiac death (p conrm the results of this meta-analysis in patients with AMI,
0.098) compared to placebo.20 Thus, carvedilol appears to have COMET has conrmed carvedilols efcacy over metoprolol
signicant antiarrhythmic effects, which may not be as prom- in patients with systolic HF.3 Thus, clearly for patients with
inent in b1-selective BBs. This would potentially lead to better systolic HF, carvedilol should be considered the BB of rst
reductions in sudden cardiac death and all-cause mortality in choice. Atenolol has not been shown to improve long-term
patients with AMIs and those with HF. In fact, sudden cardiac CV prognosis after AMI, nor has it been shown to be effective
death was signicantly reduced with carvedilol compared to for improving outcomes in patients with HF.28 Additionally,
metoprolol in the COMET trial (218 vs 262, hazard ratio 0.81, when used for hypertension, atenolol does not protect against
95% CI 0.68 to 0.97, p 0.02).21 Moreover, in a meta-analysis heart disease or reduce mortality despite lowering elevated
of >2,000 patients with HF (encompassing 19 randomized blood pressure.29 The fact that atenolol continues to be 1 of
trials), carvedilol signicantly increased left ventricular most widely prescribed BBs (presumably because of habit) is
systolic function more so than metoprolol.22 In the setting of indefensible from a scientic perspective.
HF, the b2 receptors in the heart are upregulated,23 and thus the Several important potential study limitations should
use of a b1-selective BB may not adequately protect the be considered. First, not all of the trials included in our
myocardium from excessive adrenergic tone. Carvedilol is meta-analysis were double blind (n 3), with 4 of the 11
a potent BB that blocks b1, b2, and a receptors in the heart and included trials being rated as moderate or good in quality
thereby confers comprehensive adrenergic blockade, which (i.e., Jadad score 3 of 5). Second, most trials included
may be especially advantageous for patients with HF or AMI. relatively small numbers of patients, with the exception
Carvedilol lowers blood pressure mainly through vasodi- of COMET (n 3,029), which contributed approximately
lation, whereas b1-selective BBs do so by a reduction in 94% of mortality events in the HF trials. In particular,
cardiac output (an untoward effect in patients with HF).24 our meta-analysis may have been underpowered in patients
Improved versus reduced cardiac output may allow carvedilol with AMIs to differentiate the relative benets of carvedilol
to improve insulin sensitivity, whereas atenolol and meto- compared to the other b1-selective BBs. Nevertheless,
prolol worsen insulin sensitivity.24 In the COMET study, even in the patients with AMIs (n 644), signicance in
carvedilol, compared to metoprolol, reduced the risk for favor of carvedilol therapy was present. Moreover, all hard
new diabetes development over the 5-year study by 22% outcomes showed minimal heterogeneity among trials,
(p 0.048)3. In contrast to metoprolol and atenolol, carvedilol mortality in HF (I2 0%), mortality in AMI (I2 10%)
has a neutral or favorable effect on levels of triglycerides and and nonfatal MI (I2 0%). Finally, as in most such meta-
high-density lipoprotein cholesterol.25 Additionally, in the analyses, comparing several therapeutic agents, various
Glycemic Effects in Diabetes Mellitus: Carvedilol-Metoprolol dosages of the individual agents were used, which is also
Comparison in Hypertensives (GEMINI) randomized trial, typically present in clinical situations, and generally, these
40% fewer patients progressed to microalbuminuria in the different BBs provided similar reductions in rest heart rate,
carvedilol arm than in the metoprolol arm.25 which generally indicates potential clinical efcacy.
Moreover, carvedilol has been shown to reduce cardiac
adrenergic activity, improve New York Heart Association
Disclosures
functional class, improve stroke work, and improve stroke
volume compared to atenolol and metoprolol.22,24 Addi- Dr. Lavie has served as a consultant and speaker for
tionally carvedilol exerts favorable effects on cardiac output GlaxoSmithKline, London, United Kingdom (but not
compared to the other standard nonvasodilating BBs.26 regarding b blockers). Dr. OKeefe is a speaker for

Downloaded from ClinicalKey.com at Amarillo VAMC Health Care System November 20, 2016.
For personal use only. No other uses without permission. Copyright 2016. Elsevier Inc. All rights reserved.
Review/Carvedilol Versus b1 b Blockers 769

GlaxoSmithKline and Forest Pharmaceuticals, St. Louis, 13. Metra M, Giubbini R, Nodari S, Boldi E, Modena MG, Dei Cas L.
Missouri. Differential effects of beta-blockers in patients with heart failure:
a prospective, randomized, double-blind comparison of the long-term
effects of metoprolol versus carvedilol. Circulation 2000;102:546e551.
Supplementary Data 14. Kukin ML, Kalman J, Charney RH, Levy DK, Buchholz-Varley C,
Ocampo ON, Eng C. Prospective, randomized comparison of effect of
Supplementary data related with this article can be found, in long-term treatment with metoprolol or carvedilol on symptoms,
the on-line version, at http://dx.doi.org/10.1016/j.amjcard. exercise, ejection fraction, and oxidative stress in heart failure.
2012.11.031 Circulation 1999;99:2645e2651.
15. Piccirillo G, Quaglione R, Nocco M, Naso C, Moise A, Lionetti M, Di
1. Vandvik PO, Lincoff AM, Gore JM, Gutterman DD, Sonnenberg FA, Carlo S, Marigliano V. Effects of long-term beta-blocker (metoprolol
Alonso-Coello P, Akl EA, Lansberg MG, Guyatt GH, Spencer FA. or carvedilol) therapy on QT variability in subjects with chronic heart
Primary and secondary prevention of cardiovascular disease: antith- failure secondary to ischemic cardiomyopathy. Am J Cardiol 2002;90:
rombotic therapy and prevention of thrombosis, 9th ed: American 1113e1117.
College of Chest Physicians Evidence-Based Clinical Practice Guide- 16. Tolg R, Witt M, Schwarz B, Kurz T, Kurowski V, Hartmann F, Geist
lines. Chest 2012;141:e637See668S. V, Richardt G. Comparison of carvedilol and metoprolol in patients
2. Jessup M, Abraham WT, Casey DE, Feldman AM, Francis GS, Ganiats with acute myocardial infarction undergoing primary coronary inter-
TG, Konstam MA, Mancini DM, Rahko PS, Silver MA, Stevenson ventionthe PASSAT study. Clin Res Cardiol 2006;95:31e41.
LW, Yancy CW. 2009 focused update: ACCF/AHA guidelines for the 17. Lombardo RM, Reina C, Abrignani MG, Rizzo PA, Braschi A, De
diagnosis and management of heart failure in adults: a report of the Castro S. Effects of nebivolol versus carvedilol on left ventricular
American College of Cardiology Foundation/American Heart Associ- function in patients with chronic heart failure and reduced left ventric-
ation Task Force on Practice Guidelines: developed in collaboration ular systolic function. Am J Cardiovasc Drugs 2006;6:259e263.
with the International Society for Heart and Lung Transplantation. 18. Acikel S, Bozbas H, Gultekin B, Aydinalp A, Saritas B, Bal U, Yildirir
Circulation 2009;119:1977e2016. A, Muderrisoglu H, Sezgin A, Ozin B. Comparison of the efcacy of
3. Poole-Wilson PA, Swedberg K, Cleland JG, Di Lenarda A, Hanrath P, metoprolol and carvedilol for preventing atrial brillation after coro-
Komajda M, Lubsen J, Lutiger B, Metra M, Remme WJ, Torp-Ped- nary bypass surgery. Int J Cardiol 2008;126:108e113.
ersen C, Scherhag A, Skene A. Comparison of carvedilol and meto- 19. Haghjoo M, Saravi M, Hashemi MJ, Hosseini S, Givtaj N, Ghafar-
prolol on clinical outcomes in patients with chronic heart failure in the inejad MH, Khamoushi AJ, Emkanjoo Z, Fazelifar AF, Alizadeh A,
Carvedilol or Metoprolol European Trial (COMET): randomised Sadr-Ameli MA. Optimal beta-blocker for prevention of atrial bril-
controlled trial. Lancet 2003;362:7e13. lation after on-pump coronary artery bypass graft surgery: carvedilol
4. Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gotzsche PC, Ioannidis versus metoprolol. Heart Rhythm 2007;4:1170e1174.
JP, Clarke M, Devereaux PJ, Kleijnen J, Moher D. The PRISMA 20. Dargie HJ. Effect of carvedilol on outcome after myocardial infarction
statement for reporting systematic reviews and meta-analyses of studies in patients with left-ventricular dysfunction: the CAPRICORN rando-
that evaluate healthcare interventions: explanation and elaboration. mised trial. Lancet 2001;357:1385e1390.
BMJ 2009;339:b2700. 21. Torp-Pedersen C, Poole-Wilson PA, Swedberg K, Cleland JG, Di
5. Jadad AR, Moore RA, Carroll D, Jenkinson C, Reynolds DJ, Gavaghan Lenarda A, Hanrath P, Komajda M, Lutiger B, Metra M, Remme WJ,
DJ, McQuay HJ. Assessing the quality of reports of randomized clinical Scherhag A, Skene A. Effects of metoprolol and carvedilol on cause-
trials: is blinding necessary? Control Clin Trials 1996;17:1e12. specic mortality and morbidity in patients with chronic heart failure
6. Higgins JP, Thompson SG. Quantifying heterogeneity in a meta- COMET. Am Heart J 2005;149:370e376.
analysis. Stat Med 2002;21:1539e1558. 22. Packer M, Antonopoulos GV, Berlin JA, Chittams J, Konstam MA,
7. Higgins JP, Green S. Cochrane Handbook for Systematic Reviews of Udelson JE. Comparative effects of carvedilol and metoprolol on left
Interventions Version 5.0.0. Hoboken, New Jersey: John Wiley, 2008; ventricular ejection fraction in heart failure: results of a meta-analysis.
633. Am Heart J 2001;141:899e907.
8. Mrdovic IB, Savic LZ, Perunicic JP, Asanin MR, Lasica RM, Jelena 23. Nikolaev VO, Moshkov A, Lyon AR, Miragoli M, Novak P, Paur H,
MM, Matic MD, Vasiljevic ZM, Ostojic MC. Randomized active- Lohse MJ, Korchev YE, Harding SE, Gorelik J. Beta2-adrenergic
controlled study comparing effects of treatment with carvedilol versus receptor redistribution in heart failure changes cAMP compartmenta-
metoprolol in patients with left ventricular dysfunction after acute tion. Science 2010;327:1653e1657.
myocardial infarction. Am Heart J 2007;154:116e122. 24. Martsevich SY, Kutishenko NP, Deev AD, Oganov RG, Shalnova SA.
9. Jonsson G, Abdelnoor M, Muller C, Kjeldsen SE, Os I, Westheim A. Comparison of antihypertensive and metabolic effects of carvedilol and
A comparison of the two beta-blockers carvedilol and atenolol on left metaprolol in hypertensive patients with overweight and obesity.
ventricular ejection fraction and clinical endpoints after myocardial Camellia Trial. J Hyper 2010;28:e560.
infarction. a single-centre, randomized study of 232 patients. Cardi- 25. Bakris GL, Fonseca V, Katholi RE, McGill JB, Messerli FH, Phillips
ology 2005;103:148e155. RA, Raskin P, Wright JT Jr, Oakes R, Lukas MA, Anderson KM, Bell
10. Marazzi G, Volterrani M, Caminiti G, Iaia L, Massaro R, Vitale C, DS. Metabolic effects of carvedilol vs metoprolol in patients with type
Sposato B, Mercuro G, Rosano G. Comparative long term effects of 2 diabetes mellitus and hypertension: a randomized controlled trial.
nebivolol and carvedilol in hypertensive heart failure patients. J Card JAMA 2004;292:2227e2236.
Fail 2011;17:703e709. 26. Gilbert EM, Abraham WT, Olsen S, Hattler B, White M, Mealy P, Lar-
11. Aygul N, Ozdemir K, Duzenli MA, Aygul MU. The comparative rabee P, Bristow MR. Comparative hemodynamic, left ventricular func-
effects of long-term carvedilol versus bisoprolol therapy on QT tional, and antiadrenergic effects of chronic treatment with metoprolol
dispersion in patients with chronic heart failure. Cardiology 2009;112: versus carvedilol in the failing heart. Circulation 1996;94:2817e2825.
168e173. 27. Morimoto S, Shimizu K, Yamada K, Hiramitsu S, Hishida H. Can
12. Dungen HD, Apostolovic S, Inkrot S, Tahirovic E, Topper A, Mehrhof F, beta-blocker therapy be withdrawn from patients with dilated cardio-
Prettin C, Putnikovic B, Neskovic AN, Krotin M, Sakac D, Lainscak M, myopathy? Am Heart J 1999;138:456e459.
Edelmann F, Wachter R, Rau T, Eschenhagen T, Doehner W, Anker SD, 28. Aursnes I, Osnes JB, Tvete IF, Gasemyr J, Natvig B. Does atenolol differ
Waagstein F, Herrmann-Lingen C, Gelbrich G, Dietz R. Titration to from other beta-adrenergic blockers? BMC Clin Pharmacol 2007;7:4.
target dose of bisoprolol vs. carvedilol in elderly patients with heart 29. Carlberg B, Samuelsson O, Lindholm LH. Atenolol in hypertension: is
failure: the CIBIS-ELD trial. Eur J Heart Fail 2011;13:670e680. it a wise choice? Lancet 2004;364:1684e1689.

Downloaded from ClinicalKey.com at Amarillo VAMC Health Care System November 20, 2016.
For personal use only. No other uses without permission. Copyright 2016. Elsevier Inc. All rights reserved.

Вам также может понравиться