Beta-blocker treatment in heart failure

Heart failure treatment has markedly changed during the last few decades, with demonstration of benefit of afterload reduction by vasodilator therapy and introduction of the concept of the deleterious consequences of the neuro-hormonal compensatory stimulation. Blockade of beta-adrenergic receptors, initially contra-indicated in heart failure, provide a marked reduction of mortality and morbidity in combination with diuretics and angiotensin-converting enzyme inhibitors, as demonstrated in many clinical trials. We performed a review of all clinical trials that compare beta-blockers vs. placebo in chronic heart failure. Beta-blockers with different pharmacological profiles have been tested, mainly metoprolol, bisoprolol, bucindolol and carvedilol. With progressive dose increment, tolerance of such treatment was generally good, left ventricular function improved, hospitalisations for heart failure were less frequent and mortality was reduced. The meta-analysis of the 16 randomised trials, with at least one death in each treatment group, provides a 24% relative risk reduction for such hospitalisations (95% CI=19%-29%) and 22% reduction for mortality (95% CI=16%-28%). Heterogeneity of beta-blocker effect for mortality was found and related to the non-significant benefit obtained in the BEST trial with bucindolol. When such a trial is excluded, the effect model analysis shows that relative risk reduction (beta-blocker induced benefit) is constant whatever the severity of the disease. The mechanism of beta-blocker induced benefit remains unclear, but is at least partly related to left ventricular function improvement and prevention of severe ventricular arrhythmias. In conclusion, beta-blocker treatment has become an established therapy for heart failure, in combination with diuretics and ACE inhibitors. Complementary informations will be needed to clarify the mechanism of benefit and to define the best therapeutic strategy according to the individual characteristics of patients with heart failure.