The Cardiac Insufficiency Bisoprolol Study II (CIBIS-II): a randomised trial

Beta-blocker therapy had benefits for survival in stable heart-failure patients and should not be extrapolated to patients with severe class IV symptoms and recent instability because safety and efficacy has not been established in these patients.

Abstract

SummaryBackground In patients with heart failure, β-blockade has improved morbidity and left-ventricular function, but the impact on survival is uncertain. We investigated the efficacy of bisoprolol, a β, selective adrenoceptor blocker in decreasing all-cause mortality in chronic heart failure. Methods In a multicentre double-blind randomised placebo-controlled trial in Europe, we enrolled 2647 symptomatic patients in New York Heart Association class III or IV, with left-ventricular ejection fraction of 35% or less receiving standard therapy with diuretics and inhibitors of angiotensin-converting enzyme. We randomly assigned patients bisoprolol 1·25 mg (n=1327) or placebo (n=1320) daily, the drug being progressively increased to a maximum of 10 mg per day. Patients were followed up for a mean of 1·3 years. Analysis was by intention to treat. Findings CIBIS-II was stopped early, after the second interim analysis, because bisoprolol showed a significant mortality benefit. All-cause mortality was significantly lower with bisoprolol than on placebo (156 [11·8%] vs 228 [17·3%] deaths with a hazard ratio of 0·66 (95% CI 0·54–0·81, pvs 83 [6·3%] deaths), with a hazard ratio of 0·56 (0·39–0·80, p=0·0011). Treatment effects were independent of the severity or cause of heart failure. Interpretation β-blocker therapy had benefits for survival in stable heart-failure patients. Results should not, however, be extrapolated to patients with severe class IV symptoms and recent instability because safety and efficacy has not been established in these patients.