The current role of beta-blockers in chronic heart failure: with special emphasis on the CIBIS III trial

Beta-blockers (bisoprolol, metoprolol succinate, carvedilol, and to some extent nebivolol), given on top of angiotensin-converting enzyme (ACE) inhibitors, improve survival and reduce morbidity in symptomatic stable chronic heart failure (CHF). Early beta-blockade may help to improve survival and especially prevent sudden death, but the usual practice of starting the ACE inhibitor first may lead to undertreatment with beta-blockers. The Cardiac Insufficiency Bisoprolol (CIBIS) III trial examined the optimum order of initiating CHF treatment in 1010 patients (≥65 years), with stable, mildly, or moderately symptomatic, systolic CHF. Patients were randomized to initial monotherapy with bisoprolol for up to 6 months, followed by the addition of enalapril, or the opposite sequence. Mean follow-up was 1.2 years. The bisoprolol-first and enalapril-first strategies showed similar efficacy for the combined primary endpoint of mortality or all-cause hospitalization, and similar safety. Compared with the enalapril-first strategy, the bisoprolol-first strategy significantly reduced sudden death during the first year on treatment by 46% (P < 0.05). Patients who achieved higher doses of the study drugs (particularly bisoprolol) had substantially and independently lower mortality and hospitalization risks. Thus, CIBIS III supports a free choice between bisoprolol and enalapril as initial therapy for stable, mild-to-moderate, systolic CHF, and suggests that early beta-blockade reduces the risk of sudden death in the first year.