ArticlesThe Cardiac Insufficiency Bisoprolol Study II (CIBIS-II): a randomised trial*
Introduction
Experimental and clinical trials have shown beneficial effects with β-blockade in heart failure.1, 2, 3 There is reluctance to use β-blockade therapy, however, and unequivocal evidence of benefit from randomised placebo controlled trials is needed to convince the medical community of its safety and efficacy.
Clinical trials in heart failure have tested compounds with different pharmacological profiles.2, 3 Meta-analyses of placebo-controlled trials of β-blockers have suggested an overall effect on mortality of 32%.4, 5, 6 The Cardiac Insufficiency Bisoprolol Study (CIBIS) studied bisoprolol, a highly selective antagonist of β1, adrenoceptors, which are found mainly in the heart and especially in ventricular tissue.7 That trial showed a non-significant trend towards 20% lower mortality in the bisoprolol group and 30% fewer admissions to hospital for worsening heart failure.8 We designed the CIBIS-II trial to test this evidence further, based on the CIBIS trial results.
Section snippets
Methods
The study design and protocol of CIBIS has been published.9 We did a double-blind placebo-controlled randomised trial, analysed by intention to treat.
Results
2647 patients were enrolled into the study and followed up for a mean of 1·3 years. Baseline characteristics were similar in the two groups (table 1).
The trial was stopped early because all-cause mortality was significantly less in the bisoprolol group than in the placebo group (figure 1). In the bisoprolol group, 156 (11·8%) patients died, compared with 228 (17·3%) in the placebo group (p<0·0001). The estimated annual mortality rate was 8·8% in the bisoprolol group and 13·2% in the placebo
Discussion
β-blockade had benefits for all-cause mortality in patients with chronic heart failure. Benefits were also seen for morbidity, assessed by admissions to hospital for all causes, especially for worsening heart failure.
The magnitude of the treatment effect (a 32% lower risk of mortality and admission to hospital for heart failure) is in accordance with findings from meta-analyses of previous randomised placebo-controlled trials.4 Our results were obtained in patients already taking diuretics and
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