Review
Meta-Analysis of Carvedilol Versus Beta 1 Selective Beta-Blockers (Atenolol, Bisoprolol, Metoprolol, and Nebivolol)

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Because carvedilol is a unique vasodilating β blocker (BB) exerting antioxidant activity and pleiotropic effects, it was theorized that it may confer more potent beneficial 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 β1-selective BBs used in HF (8 trials, n = 4,563), carvedilol significantly reduced all-cause mortality (risk ratio 0.85, 95% confidence interval 0.78 to 0.93, p = 0.0006). In 3 trials of patients with AMI (n = 644), carvedilol significantly reduced all-cause mortality by 45% (fixed-effects model: risk ratio 0.55, 95% confidence interval 0.32 to 0.94, p = 0.03, random-effects model: risk ratio 0.56, 95% confidence interval 0.26 to 1.12, p = 0.10), with no reduction in non-fatal MI (risk ratio 0.61, 95% confidence 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, significantly reduced all-cause mortality in systolic HF patients. Additionally, carvedilol significantly reduced all-cause mortality compared with β1-selective BBs in AMI patients using the fixed-effects model but not using the random-effects model.

Section snippets

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 systematic reviews of intervention studies was performed.4 Studies were identified through searches of the following sources: Ovid MEDLINE (1977 to 2012), PubMed (1978 to 2011), and Embase (1977 to 2012). To identify further potentially relevant studies missed by the electronic database search, reference lists from identified

Results

The search of the published research yielded 1,105 titles, of which 40 were reviewed in full text on the basis of the inclusion criteria (Figure 1). Of these, 11 studies were deemed eligible for inclusion (Figure 1).3, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17 Tables containing the characteristics of the included studies are available by request.

All trials were randomized direct comparison trials against carvedilol in patients with either HF or AMI. All background medications and baseline

Discussion

In this systematic review of 11 randomized controlled trials in 5,207 patients, we found that carvedilol significantly reduced all-cause mortality in patients with HF. Additionally, in patients with AMI, carvedilol significantly reduced all-cause mortality by fixed-effects model (but not by random-effects model) but did not reduce nonfatal MI compared to other commonly prescribed BBs, although carvedilol did demonstrate trends for reducing this end point. The preferential reduction in mortality

Disclosures

Dr. Lavie has served as a consultant and speaker for GlaxoSmithKline, London, United Kingdom (but not regarding β blockers). Dr. O'Keefe is a speaker for GlaxoSmithKline and Forest Pharmaceuticals, St. Louis, Missouri.

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