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Circulation. 2001;103:1428-1433

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(Circulation. 2001;103:1428.)
© 2001 American Heart Association, Inc.


Clinical Investigation and Reports

Heart Rate and Cardiac Rhythm Relationships With Bisoprolol Benefit in Chronic Heart Failure in CIBIS II Trial

Philippe Lechat, MD, PhD; Jean-Sébastien Hulot, MD; Sylvie Escolano, MD, PhD; Alain Mallet, PhD; Alain Leizorovicz, MD, PhD; Marie Werhlen-Grandjean, MD; Gilbert Pochmalicki, MD; Henry Dargie, MD; on behalf of the CIBIS II Investigators

From the Pharmacology Department (P.L., J.-S.H.) and INSERM, Biostatistics and Mathematical Modeling Unit (S.E., A.M.), Pitié Salpêtrière Hospital, Paris; Clinical Pharmacology Unit, Lyon Hospitals (A.L.); Merck-Lipha, Clinical Research Department, Suresnes (M.W.-G.); and Hôpital Léon Binet, Provins (G.P.), France; and Clinical Research, University of Glasgow, UK (H.D.).

Correspondence to Prof Philippe Lechat, Service de Pharmacologie, Hôpital Pitié-Salpêtrière, 47 Boulevard de l’hôpital, 75013 Paris, France. E-mail philippe.lechat{at}psl.ap-hop-paris.fr

Background—ß-Blockade–induced benefit in heart failure (HF) could be related to baseline heart rate and treatment-induced heart rate reduction, but no such relationships have been demonstrated.

Methods and Results—In CIBIS II, we studied the relationships between baseline heart rate (BHR), heart rate changes at 2 months (HRC), nature of cardiac rhythm (sinus rhythm or atrial fibrillation), and outcomes (mortality and hospitalization for HF). Multivariate analysis of CIBIS II showed that in addition to ß-blocker treatment, BHR and HRC were both significantly related to survival and hospitalization for worsening HF, the lowest BHR and the greatest HRC being associated with best survival and reduction of hospital admissions. No interaction between the 3 variables was observed, meaning that on one hand, HRC-related improvement in survival was similar at all levels of BHR, and on the other hand, bisoprolol-induced benefit over placebo for survival was observed to a similar extent at any level of both BHR and HRC. Bisoprolol reduced mortality in patients with sinus rhythm (relative risk 0.58, P<0.001) but not in patients with atrial fibrillation (relative risk 1.16, P=NS). A similar result was observed for cardiovascular mortality and hospitalization for HF worsening.

Conclusions—BHR and HRC are significantly related to prognosis in heart failure. ß-Blockade with bisoprolol further improves survival at any level of BHR and HRC and to a similar extent. The benefit of bisoprolol is questionable, however, in patients with atrial fibrillation.


Key Words: heart failure • bisoprolol • receptors, adrenergic, beta • fibrillation • heart rate




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