How to begin treatment in chronic heart failure? Results of CIBISIII

Aims To compare the effect of initial monotherapy with either bisoprolot or enalapril, followed by their combination, on mortality and hospitalization in patients with mild-to-moderate CHF. Methods and results One thousand and ten patients with mild-to-moderate CHF and left ventricular ejection fraction <= 35%, without ACE-inhibitor, beta-blocker, or angiotensin-receptor-blocker therapy were randomized to open-label monotherapy with either bisoprolot (target dose 10 mg od, n = 505) or enalapril (target dose 10 mg bid, n = 505) for 6 months, followed by their combination for 6-24 months. The combined primary endpoint was all-cause mortality or hospitalization; bisoprolol-first was considered non-inferior to enalapril-first if the upper limit of the 95% Cl for the absolute between-group difference was below +5%, corresponding to HR 1.17. In the intention-to-treat population, the primary endpoint occurred in 178 patients allocated bisoprotol-first vs. 186 allocated enalapril-first: absolute difference, -1.6%; 95% Cl, -7.6 to +4.4%; HR, 0.94; 95% Cl, 0.77-1.16. Thus, non-inferiority was demonstrated in the intention-to-treat population. In the per-protocol population, the primary endpoint occurred in 163 patients in the bisoprolol-first group vs. 165 in the enalapril-first group: absolute difference, -0.7%; 95% Cl, -6.6 to +5.1%; HR, 0.97; 95% Cl, 0.78-1.21. With bisoprolol-first, 65 patients died vs. 73 with enalapril-first (HR, 0.88; 95% Cl, 0.63-1.22; between-group difference P = 0.44), and 151 vs. 157 patients were hospitalized (HR, 0.95; 95% Cl, 0.76-1.19; between-group difference P = 0.66). Post hoc analysis of data from the first year indicated that a bisoprolol-first strategy reduced mortality by 31%, compared with an enalapril-first strategy (HR, 0.69; 95% CI, 0.46-1.02; between-group difference P = 0.065). Conclusion Initiating treatment with bisoprolot is as effective and well-tolerated as initiating treatment with enalapril. Post hoc analysis suggests that starting treatment with enalapril may reduce the risk of death, especially in the first year of treatment.