[The use of beta blockers in heart failure: clinical studies]

Abstract

Although inhibitors of angiotensin-converting enzyme (ACE) have improved the treatment of chronic heart failure (CHF), mortality related to this disorder remains unacceptably high. Results from studies started more than 25 years ago in Sweden suggested that long-term therapy with beta-blockers could improve hemodynamics and increase survival in patients with CHF; this hypothesis is confirmed by the results of six double-blind, randomized, placebo-controlled trials (MDC, CIBIS, ANZ, US Carvedilol Study, CIBIS II and MERIT-HF) who enrolled about 9000 patients with CHF. In these trials beta-blockers (metoprolol, bisoprolol or carvedilol) where added to the stable usual treatment of each patient (ACE-inhibitors, diuretics, digoxin). Baseline characteristics of patients enrolled into the beta-blocker or placebo arm were similar in all these studies. Specifically the mean patient's age was < 60 years, with a mean left ventricular ejection fraction of 25-26%, 30% of enrolled patients were in NYHA functional class II and 60% in NYHA functional class III, CHF was due to ischemic heart disease in about 60% of patients. The average follow-up for all the trials was 14.5 +/- 5.6 months. On the whole in patients on beta-blocker treatment there is a 33.3% reduction in total mortality rate, a 34.2% reduction in cardiac death rate, a 37.7% reduction in sudden death rate, and a 41.7% reduction in worsening heart failure mortality rate. Moreover, in beta-blocker patients there is a 31.7% reduction in all-cause readmissions to hospital and a 26% reduction in the combined end point (total mortality and hospital readmission). Beta-blockers improved ventricular function but there was no significant improvement in functional capacity. In conclusion, the results of the six trials considered indicate that there is convincing evidence supporting a favorable effect of beta-blockade on the risk of death and readmission to hospital in patients with dilated cardiomyopathy with systolic dysfunction, aged < 70 years, in NYHA functional class II-III. The effects of these drugs in CHF patients a) with normal left ventricular ejection fraction, b) aged > 65-70 years, c) in NYHA functional class IV, and d) with comorbilities such as obstructive lung disease, diabetes, peripheral arterial diseases, require additional study.