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-blocker to obtain a benefit in terms of survival remains uncertain.
Methods and Results: We classified by tertile the 2647 patients enrolled in CIBIS II according to the last tolerated dose: low dose (LD: 1.25, 2.5 or 3.75mg/day, n=434), moderate dose (MD: 5 or 7.5mg/day, n=328) and high dose (HD: 10mg/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 bisoprolol 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 bisoprolol therapy based on the individual patient's tolerability.