β-Adrenergic blocking agents in heart failure: Benefits of vasodilating and nonvasodilating agents according to patients' characteristics: A meta- analysis of clinical trials

Background: In patients with heart failure, β-adrenergic blocking agents reduce overall and cardiovascular mortality. This meta-analysis aimed at clarifying their effect on sudden death, the magnitude of their benefit according to the cause of heart failure, and whether there is any difference between vasodilating and nonvasodilating agents. Methods: Randomized, clinical trials were included if they evaluated a β-adrenergic blocking agent without intrinsic sympathomimetic activity, included a control group receiving placebo or standard treatment, evaluated mortality on an intention- to-treat basis, and lasted at least 8 weeks. Results: Twenty-one trials with 5849 patients (3130 receiving β-blockers) were included. Median length of treatment was 6 months. Most patients had mild or moderate heart failure and were treated with angiotensin-converting enzyme inhibitors, diuretics, and digitalis. The β-blockers significantly reduced overall mortality, cardiovascular mortality, and mortality due to pump failure and sudden death by 34% to 39%. The decrease in overall mortality in patients with ischemic heart disease (IHD) (30%) was no different from that among patients with non- IHD (26%) (P = .08). The reduction in overall mortality was greater with vasodilating than with nonvasodilating agents (45% vs 27%; P = .007), particularly in patients without IHD (62%), compared with those with IHD (22%; P = .03). Conclusions: In patients with heart failure, β-blockers reduce total and cardiovascular mortality at the expense of a decrease in mortality due to pump failure and sudden death. The magnitude of the benefit is similar in patients with IHD and in those with non-IHD. Vasodilating β- blockers have a greater effect on overall mortality than nonvasodilating agents, particularly in patients with non-IHD.