The Safety of Amiodarone in Patients With Heart Failure

Torp-Pedersen, Christian; Metra, Marco; Spark, Philip; Lukas, Mary Ann; Moullet, Christine; Scherhag, Armin; Komajda, Michel; Cleland, John G.F.; Remme, Willem; Di Lenarda, Andrea; Swedberg, Karl; Poole-Wilson, Philip A.; for the COMET Investigators,

doi:10.1016/j.cardfail.2007.02.009

« Previous Next »Journal of Cardiac Failure
Volume 13, Issue 5 , Pages 340-345, June 2007

The Safety of Amiodarone in Patients With Heart Failure

Christian Torp-Pedersen, MD
- From the Department of Cardiology, Bispebjerg University Hospital, Copenhagen, Denmark
- Reprint requests: Prof. Christian Torp-Pedersen, Department of Cardiology, Bispebjerg University Hospital, 2400 Copenhagen NV, Denmark.
Marco Metra, MD
- Cattedra di Cardiologia, Università di Brescia, Italy
Philip Spark, PhD
- Nottingham Clinical Research Group (NCRG), Nottingham, UK
Mary Ann Lukas, MD
- GlaxoSmikthKline, Philadelphia, Pennsylvania
Christine Moullet, MD
- F. Hoffmann-La Roche, Basel, Switzerland
Armin Scherhag, MD
- I Medical Clinic, University Hospital Mannheim, University of Heidelberg, Germany and F. Hoffmann-La Roche, Basel, Switzerland
Michel Komajda, MD
- La Pitié-Salpétriêre Hospital, Paris, France
John G.F. Cleland, MD
- Department of Cardiology, University of Hull, Kingston upon Hull, UK
Willem Remme, MD
- Sticares Cardiovascular Research Foundation, Rhoon, Netherlands
Andrea Di Lenarda, MD
- Department of Cardiology, Ospedale di Cattinara, Trieste, Italy
Karl Swedberg, MD
- Department of Medicine, Sahlgrenska University Hospital/Östra, Göteborg, Sweden
Philip A. Poole-Wilson, MD
- National Heart and Lung Institute, Imperial College London, UK
- The COMET investigators are listed in a previous publication: Poole-Wilson PA, Swedberg K, Cleland JG, et al. Comparison of carvedilol and metoprolol on clinical outcomes in patients with chronic heart failure in the Carvedilol Or Metoprolol European Trial (COMET): randomized controlled trial. Lancet 2003;362:7–13.
for the COMET Investigators

Received 26 October 2006; received in revised form 23 February 2007; accepted 28 February 2007.

Copenhagen, Denmark; Brescia, Italy; Nottingham, United Kingdom; Basel, Switzerland; Heidelberg, Germany; Paris, France; Kingston upon Hull, United Kingdom; Rhoon, Netherlands; Göteborg, Sweden; London, United Kingdom

Abstract

Background

Uncertainty persists about the safety and efficacy of amiodarone for the management of heart failure.

Methods and Results

We randomized 3029 patients with chronic heart failure to receive carvedilol or metoprolol and followed patients for a median of 58 months. One hundred fifty-five of 1466 patients in New York Heart Association (NYHA) Class II and 209 of 1563 in Class III or IV received amiodarone at baseline. Persistence with amiodarone treatment was high and 66% received amiodarone after 4 years. During follow-up, 38.7% and 58.9% of patients receiving amiodarone in NYHA Classes II and III + IV died versus 26.2% and 43.3% not receiving amiodarone (P < .001). This difference was maintained in multivariable analysis (hazard ratio [HR] 1.5, 95% confidence interval [CI] 1.2–1.7, P < .001). The difference was explained by an increased risk of death due to circulatory failure (HR 2.4, CI 1.9–3.1, P < .001) in patients receiving amiodarone. Sudden death was not different (HR 1.07, CI 0.8–1.4, P = .7). The increased risk was similar across NYHA classes with HR of 1.60 (CI 1.2–2.1, P < .001) in NYHA Class II versus 1.58 (CI 1.3–1.9, P < .001) in Classes III + IV.