Effect on Survival and Hospitalization of Initiating Treatment for Chronic Heart Failure With Bisoprolol Followed by Enalapril, as Compared With the Opposite Sequence: Results of the Randomized Cardiac Insufficiency Bisoprolol Study (CIBIS) III

R. Willenheimer
2005 Circulation  
on behalf of the CIBIS III Investigators Background-In patients with chronic heart failure (CHF), a ␤-blocker is generally added to a regimen containing an angiotensin-converting-enzyme (ACE) inhibitor. It is unknown whether ␤-blockade as initial therapy may be as useful. Methods and Results-We randomized 1010 patients with mild to moderate CHF and left ventricular ejection fraction Յ35%, who were not receiving ACE inhibitor, ␤-blocker, or angiotensin receptor blocker therapy, to open-label
more » ... , to open-label monotherapy with either bisoprolol (target dose 10 mg QD; nϭ505) or enalapril (target dose 10 mg BID; nϭ505) for 6 months, followed by their combination for 6 to 24 months. The 2 strategies were blindly compared with regard to the combined primary end point of all-cause mortality or hospitalization and with regard to each of these end point components individually. Bisoprolol-first treatment was noninferior to enalapril-first treatment if the upper limit of the 95% confidence interval (CI) for the absolute between-group difference was Ͻ5%, corresponding to a hazard ratio (HR) of 1.17. In the intention-to-treat sample, the primary end point occurred in 178 patients allocated to bisoprolol-first treatment versus 186 allocated to enalapril-first treatment (absolute difference Ϫ1.6%, 95% CI Ϫ7.6 to 4.4%, HR 0.94; 95% CI 0.77 to 1.16). In the per-protocol sample, 163 patients allocated to bisoprolol-first treatment had a primary end point, versus 165 allocated to enalapril-first treatment (absolute difference Ϫ0.7%, 95% CI Ϫ6.6 to 5.1%, HR 0.97; 95% CI 0.78 to 1.21). With bisoprolol-first treatment, 65 patients died, versus 73 with enalapril-first treatment (HR 0.88; 95% CI 0.63 to 1.22), and 151 versus 157 patients were hospitalized (HR 0.95; 95% CI 0.76 to 1.19). Conclusion-Although noninferiority of bisoprolol-first versus enalapril-first treatment was not proven in the per-protocol analysis, our results indicate that it may be as safe and efficacious to initiate treatment for CHF with bisoprolol as with enalapril. (Circulation. 2005;112:2426-2435.)
doi:10.1161/circulationaha.105.582320 pmid:16143696 fatcat:b4xdbfgdv5hpplpb3p2vlfg3le