Amiodarone Interaction With beta-Blockers

Analysis of the Merged EMIAT (European Myocardial Infarct Amiodarone Trial) and CAMIAT (Canadian Amiodarone Myocardial Infarction Trial) Databases

Boutitie, Florent PhD
Boissel, Jean-Pierre MD
Connolly, Stuart J. FRCPC
Camm, A. John MD
Cairns, John A. MD
Julian, Desmond G. MD
Gent, Michael DSc
Janse, Michiel J. MD
Dorian, Paul MD
Frangin, Gerald MD

The EMIAT and CAMIAT Investigators.
Received August 4, 1998; revision received January 20, 1999; accepted January 20, 1999.
From the Clinical Pharmacology Department, Claude Bernard University, Lyon, France (F.B., J.-P.B.); the Department of Medicine (S.C., J.A.C.) and Clinical Epidemiology and Biostatistics (M.G.), McMaster University, Hamilton, Ontario, Canada; the Department of Medicine, University of Toronto, Ontario, Canada (P.D.); Cardiological Sciences, St George's Hospital Medical School, London, UK (A.J.C.); Netherhall Gardens, London, UK (D.G.J.); the Department of Clinical and Experimental Cardiology, Academic Medical Centre, Amsterdam, Netherlands (M.J.J.); and Sanofi Recherche, Montpellier, France (G.F.).
Correspondence to Prof Jean-Pierre Boissel, Service de Pharmacologie Clinique, EA 643, 162 Avenue Lacassagne, BP 3041, 69394 Lyon Cedex 03, France. E-mail [email protected].

Circulation 99(17):p 2268-2275, May 4, 1999.

Background

Investigations with in vitro and animal models suggest an interaction between amiodarone and beta-blockers. The objective of this work was to explore if an interaction with beta-blocker treatment plays a role in the decrease of cardiac arrhythmic deaths with amiodarone in patients recovered from an acute myocardial infarction.

Methods and Results-A pooled database from 2 similar randomized clinical trials, the European Amiodarone Myocardial Infarction Trial (EMIAT) and the Canadian Amiodarone Myocardial Infarction Trial (CAMIAT), was used. Four groups of post-myocardial infarction patients were defined: beta-blockers and amiodarone used, beta-blockers used alone, amiodarone used alone, and neither used. All analyses were done on an intention-to-treat basis. Unadjusted and adjusted relative risks for all-cause mortality, cardiac death, arrhythmic cardiac death, nonarrhythmic cardiac death, arrhythmic death, or resuscitated cardiac arrest were lower for patients receiving beta-blockers and amiodarone than for those without beta-blockers, with or without amiodarone. The interaction was statistically significant for cardiac death and arrhythmic death or resuscitated cardiac arrest (P=0.05 and 0.03, respectively). Findings were consistent across subgroups.

Conclusions

These findings are based on a post hoc analysis. However, they confirm prior results from in vitro and animal experiments suggesting an interaction between beta-blockers and amiodarone. In practice, not only is the adjunct of amiodarone to beta-blockers not hazardous, but beta-blocker therapy should be continued if possible in patients in whom amiodarone is indicated. (Circulation. 1999;99:2268-2275.)