Bisoprolol dose-response relationship in patients with congestive heart failure: a subgroup analysis in the cardiac insufficiency bisoprolol study (CIBIS II)

Aims Whether all patients with congestive heart failure (CHF) need to reach the target dose of beta-biocker to obtain a benefit in terms of survival remains uncertain. Methods and results We classified by tertile the 2647 patients enrolled in CIBIS 11 according to the last tolerated dose: low dose (LD: 1.25, 2.5 or 3.75 mg/day, n=434), moderate dose (MD: 5 or 7.5 mg/day, n=328) and high dose (HD: 10 mg/day, n=565) of bisoprolol or placebo (LD=234, MD=278 and HD=808). In both groups, patients tolerating only low doses were significantly older with more severe New York Heart Association (NYHA) functional class and higher frequency of co-morbidities. Treatment withdrawal was associated with a significant increase of mortality in the bisoprolol group (relative hazard (RH)=2.13, 95% confidence interval (CI)=1.43-3.17, p=0.0002). After adjustment, all-cause mortality was significantly reduced in the bisoprolot group compared to placebo regardless of the dose level considered: LD (RH=0.66, 95% CI=0.48-0.92), MD (RH=0.33, 95% CI=0.21-0.51) or HD (RH=0.59, 95% CI=0.40-0.89). Conclusions Bisoprolol reduces mortality in CHF patients at all tolerated dose levels and its withdrawal increases the risk of mortality. Efforts should be made to maintain bisoprolot therapy based on the individual patient's tolerability. (C) 2003 The European Society of Cardiology. Published by Elsevier Science Ltd. All rights reserved.