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Carvedilol superior to metoprolol for preventing death from CHF

J Fam Pract. 2003 November;52(11):828-848
By
Beth A. Damitz, MD
Richard W. Lord, Jr, MD
Linda N. Meurer, MD, MPH
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  • BACKGROUND: Strong evidence supports the addition of a beta-blocker for reducing mortality and hospitalization rates in patients with heart failure, and some studies suggest that the nonselective beta-blocker carvedilol has a greater effect on cardiovascular indices than beta-1 selective beta blockers.
  • POPULATION STUDIED: The investigators enrolled 3029 patients with symptomatic mild to severe chronic heart failure from 341 centers in 15 European countries. Eligible patients had documented left ventricular ejection fraction of 35% or less and at least 1 cardiovascular admission during the previous 2 years. All were on stable heart failure treatment with ACE inhibitors for at least 4 weeks unless contraindicated, and on treatment with diuretics for at least 2 weeks.
  • STUDY DESIGN AND VALIDITY: Using a double-blind randomized design, the researchers randomly assigned 1511 patients with symptomatic chronic heart failure to treatment with carvedilol and 1518 to metoprolol. During an initial titration phase, the dose of each beta-blocker was increased to a target dose of carvedilol 25 mg twice daily or metopro-lol 50 mg twice daily. Investigators at each site were given numbered treatment kits and were told to start with the lowest-numbered kit so that allocation was concealed. Patients were then assessed every 4 months for an average of 58 months. Data were analyzed on an intention-to-treat basis. Patients who were lost to follow-up (5) or who withdrew their consent (28) were included up to the last known date of consensual contact.
  • OUTCOMES MEASURED: The primary endpoints were all-cause mortality and the composite endpoint of all-cause mortality or all-cause admission.
  • RESULTS: At the end of the study, 34% of the patients on carvedilol died, compared with 40% of those on metoprolol. Adjusting for potential confounders, 15 patients would have to be treated with carvedilol instead of metoprolol for almost 5 years to prevent 1 death (number needed to treat=14.7; 95% confidence interval, 9.6–35.7). Combined mortality and hospitalization rates were not statistically significantly different between the 2 groups.
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PRACTICE RECOMMENDATIONS

Among white patients with symptomatic systolic dysfunction on stable treatment with diuretics and angiotensin-converting enzyme (ACE) inhibitors, the addition of the nonselective beta-blocker carvedilol extends survival by 17% per year compared with metoprolol. This benefit translates into a number needed to treat (NNT) of 17 for 5 years. This extrapolates to an added 1.4 years of life.

It is unclear whether this benefit holds true for nonwhite patients. Carvedilol should be considered over metoprolol for treating patients with congestive heart failure to improve survival.

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