Benefits of β blockers in patients with heart failure and reduced ejection fraction: network meta-analysis OPEN ACCESS

Objective To clarify whether any particular β blocker is superior in patients with heart failure and reduced ejection fraction or whether the benefits of these agents are mainly due to a class effect. Design Systematic review and network meta-analysis of efficacy of different β blockers in heart failure. Data sources CINAHL(1982-2011), Cochrane Collaboration Central Register of Controlled Trials (-2011), Embase (1980-2011), Medline/PubMed (1966-2011), and Web of Science (1965-2011). Study selection Randomized trials comparing β blockers with other β blockers or other treatments. Data extraction The primary endpoint was all cause death at the longest available follow-up, assessed with odds ratios and Bayesian random effect 95% credible intervals, with independent extraction by observers. Results 21 trials were included, focusing on atenolol, bisoprolol, bucindolol, carvedilol, metoprolol, and nebivolol. As expected, in the overall analysis, β blockers provided credible mortality benefits in comparison with placebo or standard treatment after a median of 12 months (odds ratio 0.69, 0.56 to 0.80). However, no obvious differences were found when comparing the different β blockers head to head for the risk of death, sudden cardiac death, death due to pump failure, or drug discontinuation. Accordingly, improvements in left ventricular ejection fraction were also similar irrespective of the individual study drug. Conclusion The benefits of β blockers in patients with heart failure with reduced ejection fraction seem to be mainly due to a class effect, as no statistical evidence from current trials supports the superiority of any single agent over the others. Introduction According to the American Heart Association, heart failure affects nearly 8.26 million Americans and accounts for 32.8% of cardiovascular related deaths. β blockers have been one of the mainstays of treatment because of their ability to reverse the neurohumoral effects of the sympathetic nervous system, with ensuing prognostic and symptomatic benefits, and different societies have thus included them in guidelines for management of heart failure. Specifically, β adrenergic blockers have been shown in randomized trials to prolong survival, prevent arrhythmia, improve symptoms of heart failure and left ventricular ejection fraction, and control ventricular rate, especially in patients with chronic heart failure. However, controversy exists as to the optimal selection of a particular β blocker for management of heart failure, as the available β blockers differ in their selectivity for adrenergic receptors and their effects on the peripheral circulation. In addition, several of the available studies had a small sample size with a short duration of follow-up, thereby limiting their inferential capacity, and publishedmeta-analyses have evaluated the role of β blockers in heart failure with reduced ejection fraction in terms of clinical and echocardiographic endpoints. Moreover, few studies have attempted to answer another crucial and debated question—that is, the tolerability of β blockers in heart failure. More importantly, the question of the superior efficacy of a given β blocker over others in preventing clinically relevant endpoints has never been assessed in the comprehensive setting of a systematic review, as only one trial has directly compared carvedilol and metoprolol tartrate. Correspondence to: S Chatterjee, 40 Roger Williams Green Apt 40 RWG, Providence, RI 02904, USA [email protected] Extra material supplied by the author (see http://www.bmj.com/content/346/bmj.f55?tab=related#webextra) No commercial reuse: See rights and reprints http://www.bmj.com/permissions Subscribe: http://www.bmj.com/subscribe BMJ 2013;346:f55 doi: 10.1136/bmj.f55 (Published 16 January 2013) Page 1 of 10