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CLINICAL RESEARCH: HEART FAILURE

Carvedilol Protects Better Against Vascular Events Than Metoprolol in Heart Failure

Results From COMET

Willem J. Remme, MD, PhD, FACC, FAHA, FESC^_*,_*, Christian Torp-Pedersen, MD, FESC, FACC, John G.F. Cleland, MD, FRCP, FESC, FACC, Philip A. Poole-Wilson, MD, FRCP, FESC, FACC, Marco Metra, MD^||, Michel Komajda, MD, PhD, FESC^¶, Karl Swedberg, MD, PhD, FESC, FACC^#, Andrea Di Lenarda, MD, FESC^_**, Phillip Spark, BSc (Hons), Armin Scherhag, MD, Christine Moullet, MD and Mary Ann Lukas, MD

^_* Sticares Cardiovascular Research Institute, Rhoon, the Netherlands
Bispebjerg University Hospital, Copenhagen, Denmark
University of Hull, Kingston-upon-Hull, United Kingdom
National Heart and Lung Institute, Imperial College, London, United Kingdom
^|| Department of Cardiology, University of Brescia, Brescia, Italy
^¶ Pitié Salpetrière Hospital, Paris, France
^# Sahlgrenska University Hospital, Gothenburg, Sweden
^_** Ospedale di Cattinara, University of Trieste, Trieste, Italy
Nottingham Clinical Research Group, Nottingham, United Kingdom
F. Hoffmann-La Roche, Basel, Switzerland
GlaxoSmithKline, Philadelphia, Pennsylvania

Manuscript received August 17, 2006; revised manuscript received October 26, 2006, accepted October 30, 2006.

^_* Reprint requests and correspondence: Dr. Willem J. Remme, Sticares Cardiovascular Research Foundation, P.O. Box 882, 3160 AB Rhoon, the Netherlands. (Email: w.j.remme{at}sticares.org).

OBJECTIVES: We explored whether vascular protection by carvedilol could contribute to its superior effects in the treatment of heart failure (HF) compared with metoprolol tartrate in the COMET (Carvedilol Or Metoprolol European Trial) study.

BACKGROUND: Full adrenergic blockade by carvedilol and additional (e.g., antioxidative) properties may lead to vascular protection relative to beta-1 blockade alone, and contribute to its efficacy in HF treatment.

METHODS: Three thousand twenty-nine patients with HF due to ischemic (51%) or idiopathic cardiomyopathy (44%) were randomized double-blind to carvedilol (n = 1,511) or metoprolol (n = 1,518) and followed for 58 months. Vascular end points were cardiovascular death, stroke, stroke death, myocardial infarction (MI), and unstable angina.

RESULTS: The effect of carvedilol on cardiovascular death improved consistently in subgroups with prespecified baseline variables. Myocardial infarctions were reported in 69 carvedilol and 94 metoprolol patients (hazard ratio [HR] 0.71, 95% confidence interval [CI] 0.52 to 0.97, p = 0.03). Cardiovascular death or nonfatal MI combined were reduced by 19% in carvedilol (HR 0.81, 95% CI 0.72 to 0.92, p = 0.0009 vs. metoprolol). Unstable angina was reported as an adverse event in 56 carvedilol and in 77 metoprolol patients (HR 0.71, 95% CI 0.501 to 0.998, p = 0.049). A stroke occurred in 65 carvedilol and 80 metoprolol patients (HR 0.79, 95% CI 0.57 to 1.10). Stroke or MI combined occurred in 130 carvedilol and 168 metoprolol patients (HR 0.75, 95% CI 0.60 to 0.95, p = 0.015), and fatal MI or fatal stroke occurred in 34 carvedilol and in 72 metoprolol patients (HR 0.46, 95% CI 0.31 to 0.69, p = 0.0002). Death after a nonfatal MI or stroke occurred in 61 of 124 carvedilol and in 106 of 160 metoprolol patients (HR 0.66, 95% CI 0.48 to 0.90, p = 0.0086).

CONCLUSIONS: Carvedilol improves vascular outcomes better than metoprolol. These results suggest a ubiquitous protective effect of carvedilol against major vascular events.

Abbreviations and Acronyms   ACE = angiotensin-converting enzyme   CI = confidence interval   HF = heart failure   HR = hazard ratio   LVEF = left ventricular ejection fraction   MI = myocardial infarction   NYHA = New York Heart Association

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