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European Heart Journal Advance Access published online on July 21, 2005
European Heart Journal, doi:10.1093/eurheartj/ehi386
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European Heart Journal © The European Society of Cardiology 2005; all rights reserved
Received August 25, 2004
Revised May 16, 2005
Accepted June 2, 2005

Clinical research

Influence of heart rate, blood pressure, and beta-blocker dose on outcome and the differences in outcome between carvedilol and metoprolol tartrate in patients with chronic heart failure: results from the COMET trial

Marco Metra 1*, Christian Torp-Pedersen 2, Karl Swedberg 3, John G.F. Cleland 4, Andrea Di Lenarda 5, Michel Komajda 6, Willem J. Remme 7, Beatrix Lutiger 8, Armin Scherhag 9, Mary Ann Lukas 10, Andrew Charlesworth 11, Philip A. Poole-Wilson 12, and for the COMET investigators

1 Cattedra di Cardiologia, Università di Brescia, c/o Spedali Civili, P.zza Spedali Civili, 25100 Brescia, Italy
2 Department of Cardiology, Bispebjerg University Hospital, Copenhagen, Denmark
3 Department of Medicine, Sahlgrenska University Hospital/Östra, Göteborg, Sweden
4 Department of Cardiology, University of Hull, Kingston upon Hull, UK
5 Department of Cardiology, Ospedale di Cattinara, Trieste, Italy
6 Department of Cardiology, La Pitié-Salpétrière Hospital, Paris, France
7 Sticares Cardiovascular Research Foundation, Rhoon, The Netherlands
8 F. Hoffmann La Roche, Basel, Switzerland
9 F. Hoffmann La Roche, Basel, Switzerland; I Medical Clinic, University Hospital Mannheim, University of Heidelberg, Germany
10 GlaxoSmithKline Philadelphia, PA, USA
11 Nottingham Clinical Research Group, Nottingham, UK
12 National Heart and Lung Institute, Imperial College London, UK

* To whom correspondence should be addressed.
Marco Metra, E-mail: metramarco{at}libero.it


  Abstract

Aims We studied the influence of heart rate (HR), systolic blood pressure (SBP), and beta-blocker dose on outcome in the 2599 out of 3029 patients in Carvedilol Or Metoprolol European Trial (COMET) who were alive and on study drug at 4 months after randomization (time of first visit on maintenance therapy).

Methods and results By multivariable analysis, baseline HR, baseline SBP, and their change after 4 months were not independently related to subsequent outcome. In a multivariable analysis including clinical variables, HR above and SBP below the median value achieved at 4 months predicted subsequent increased mortality [relative risk (RR) for HR > 68 b.p.m. 1.333; 95% confidence intervals (CI) 1.152-1.542; P < 0.0001 and RR for SBP > 120 mmHg 0.78; 95% CI 0.671-0.907; P < 0.0013]. Achieving target beta-blocker dose was associated with a better outcome (RR 0.779; 95% CI 0.662-0.916; P < 0.0025). The superiority of carvedilol as compared to metoprolol tartrate was maintained in a multivariable model (RR 0.767; 95% CI 0.663-0.887; P = 0.0004) and there was no interaction with HR, SBP, or beta-blocker dose.

Conclusion Beta-blocker dose, HR, and SBP achieved during beta-blocker therapy have independent prognostic value in heart failure. None of these factors influenced the beneficial effects of carvedilol when compared with metoprolol tartrate at the pre-defined target doses used in COMET.

Keywords: Heart failure; Trials; Beta-blockers.
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