What is the clinical evidence from this study?

Study design: RCT. Population: congestive heart failure (n=2647). Intervention: Bisoprolol vs. Placebo. Primary outcome: all-cause mortality (RH 0.66, 95% CI 0.48-0.92).

March 1, 2003Open Access

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

Key Result

Bisoprolol significantly reduced all-cause mortality compared to placebo in patients with congestive heart failure at all tolerated dose levels, including low doses (RH 0.66; 95% CI 0.48-0.92).

Study Design

Type

RCT (n=2,647)

Structured PICO

Does bisoprolol reduce mortality in patients with congestive heart failure at all tolerated dose levels compared to placebo?

Population

2,647 patients with congestive heart failure enrolled in the CIBIS II trial, classified by their last tolerated dose of bisoprolol or placebo.

Intervention

Bisoprolol at low dose (1.25, 2.5 or 3.75 mg/day), moderate dose (5 or 7.5 mg/day), or high dose (10 mg/day)

Comparator

Placebo at corresponding dose levels

Outcome

All-cause mortalityhard clinical

Bisoprolol reduces mortality in patients with congestive heart failure at all tolerated dose levels, suggesting that maintaining therapy at a tolerated dose is beneficial even if the target dose cannot be reached.

Main Result

Hazard Ratio: 0.66 (95% CI 0.48–0.92)

Abstract

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.