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European Journal of Heart Failure 2005 7(4):640-649; doi:10.1016/j.ejheart.2004.09.010
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© 2005 European Society of Cardiology

Exchange of β-blockers in heart failure patients. Experiences from the poststudy phase of COMET (the Carvedilol or Metoprolol European Trial)

Andrea Di Lenardaa,*, Willem J. Remmeb, Andrew Charlesworthc, John G.F. Clelandd, Beatrix Lutigere, Marco Metraf, Michel Komajdag, Christian Torp-Pedersenh, Armin Scherhage, Karl Swedbergi, Philip A. Poole-Wilsonj and for the COMET investors

a Department of Cardiology, Ospedale di Cattinara Strada di Fiume 447, 34100 Trieste, Italy
b Sticares Cardiovascular Research Foundation Rhoon, The Netherlands
c Stat Nottingham Clinical Research Group (NCRG) Nottingham, UK
d Department of Cardiology, University of Hull Kingston upon Hull, UK
e F. Hoffmann La Roche Basel, Switzerland
f Cattedra di Cardiologia, Università di Brescia, Italy
g Department of Cardiology, La Pitié-Salpétrière Hospital Paris, France
h Department of Cardiology, Bispebjerg University Hospital Copenhagen, Denmark
i Dept. of Medicine, Sahlgrenska University Hospital/Östra Göteborg, Sweden
j National Heart and Lung Institute, Imperial College London UK

* Corresponding author. Tel.: +39 040 3994866; Fax: +39 040 3994878. E-mail address: dilenar{at}univ.ts.it


  Abstract

Background: The Carvedilol or Metoprolol European Trial (COMET) reported a significant survival benefit for carvedilol, a β1-, β2- and {alpha}1-blocker, vs. metoprolol tartrate, a β1-selective blocker, in patients with mild-to-severe chronic heart failure (CHF). Patients on treatment with metoprolol might benefit from switching to carvedilol.

Aim: To investigate the safety and tolerability of switching β-blockers in CHF.

Methods: At the end of COMET, the Steering Committee recommended that study medication was stopped without unblinding, and patients were commenced on open-label β-blockade at a dose equivalent to half the dose of blinded therapy, with subsequent titration to target or maximum tolerated dose. Patients were followed for 30 days.

Results: 1321 out of 1440 patients were transitioned to open-label treatment (76.8% to carvedilol). Serious adverse and CHF-related events were respectively 9.4% and 4.7% in those switching from carvedilol to metoprolol and 3.1% and 1.5% in patients switching from metoprolol to carvedilol. Patients who switched from carvedilol to metoprolol showed the highest mortality or hospitalisation rate (12.3%) in comparison with those who switched from metoprolol to carvedilol (3.1%, p<0.001) or who stayed on the same drug (carvedilol: 2.5%, p<0.001; metoprolol: 4.2%, p=0.04). Reducing the initial dose of the second β-blocker maximised the safety of this strategy. Event rate was higher in patients with more severe heart failure and in those withdrawing from β-blockade.

Conclusion: Our data show that switching β-blockers is a practical, safe and well-tolerated strategy to optimise treatment of CHF. Patients who switched to carvedilol showed the lowest rate of adverse events. A closer clinical monitoring is recommended during transition in high-risk patients.

Key Words: Heart failure • β-blockers • Carvedilol • Metoprolol • Dosage • Adverse event

Received April 5, 2004; Revised September 9, 2004; Accepted September 20, 2004


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