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European Heart Journal Advance Access originally published online on July 21, 2005
European Heart Journal 2005 26(21):2259-2268; doi:10.1093/eurheartj/ehi386
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© The European Society of Cardiology 2005. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

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 Metra1,*, Christian Torp-Pedersen2, Karl Swedberg3, John G.F. Cleland4, Andrea Di Lenarda5, Michel Komajda6, Willem J. Remme7, Beatrix Lutiger8, Armin Scherhag8,9, Mary Ann Lukas10, Andrew Charlesworth11, Philip A. Poole-Wilson12 for the COMET investigators{dagger}

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

Received 25 August 2004; revised 16 May 2005; accepted 2 June 2005; online publish-ahead-of-print 21 July 2005.

* Corresponding author: Cattedra di Cardiologia, c/o Spedali Civili, P.zza Spedali Civili, 25100 Brescia, Italy. Tel: +39 30 3995572; fax: +39 30 3700359. E-mail address: metramarco{at}libero.it

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.

Key Words: Heart failure • Trials • Beta-blockers


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