[Clinical trials of beta-blockers in heart failure: history, overview and future prospects]

Although beta-blockers have been classically contraindicated in heart failure patients, their administration at progressively increasing doses provides long-term benefit in such patients with altered left ventricular function, and prevents the direct and indirect deleterious cardiac effects of catecholamines. By improving left ventricular function and preventing severe arrhythmias, beta-blockade improves survival, reduces the occurrence of sudden death and hospital admissions for worsening heart failure. The degree of benefit is dose dependent, although few prospective data confirm this fact. Among tested compounds, bisoprolol, metoprolol and carvedilol have produced similar improvements in survival with a 34% reduction in mortality in large-scale clinical trials. Bucindolol, however, did not significantly improve survival in the BEST trial. Different hypotheses may explain such results. In terms of therapeutic strategy, beta-blocker treatment must be initiated in stabilised patients already receiving diuretics and an angiotensin-converting enzyme inhibitor. Ongoing studies are evaluating the potential benefit of starting treatment first with beta-blockers in order to better prevent sudden death, particularly as this most often occurs in the early stages of the disease.