CLINICAL STUDY
Metoprolol controlled release/extended release in patients with severe heart failure
Analysis of the experience in the MERIT-HF study
Sidney Goldstein, MD*,
Björn Fagerberg, MD, PhD ,
Åke Hjalmarson, MD, PhD ,
John Kjekshus, MD, PhD ,
Finn Waagstein, MD, PhD,
Hans Wedel, PhD||,
John Wikstrand, MD, PhD for the MERIT-HF Study Group1
* Henry Ford Heart and Vascular Institute, Henry Ford Hospital, Detroit, Michigan, USA
Wallenberg Laboratory for Cardiovascular Research, Sahlgrenska University Hospital, Göteborg, Sweden
Department of Cardiology, Sahlgrenska University Hospital, Göteborg, Sweden
Section of Cardiology, Rikshospitalet, Oslo, Norway
|| Nordic School of Public Health, Göteborg, Sweden
Manuscript received February 5, 2001;
revised manuscript received June 11, 2001,
accepted June 28, 2001.
Reprint requests and correspondence: Dr. Sidney Goldstein, Division of Cardiovascular Medicine, Henry Ford Hospital, 2799 West Grand Boulevard, Detroit, Michigan 48202-2689
SGOLDST1{at}HFHS.ORG
OBJECTIVES
This study analyzed the effect of the beta1-selective beta-blocker metoprolol succinate controlled release/extended release (CR/XL) once daily on mortality, hospitalizations and tolerability in patients with severe heart failure.
BACKGROUND
There continues to be resistance to the incorporation of beta-blockers into clinical care, largely due to concerns about their benefit in patients with more severe heart failure.
METHODS
A subgroup of patients from Metoprolol CR/XL Randomized Intervention Trial in chronic Heart Failure (MERIT-HF) in New York Heart Association (NYHA) functional class III/IV with left ventricular ejection fraction <0.25 were identified (n = 795). The analysis was by intention-to-treat.
RESULTS
The mean ejection fraction at baseline was 0.19, and the yearly placebo mortality during follow-up was 19.1%. Treatment with metoprolol CR/XL compared to placebo resulted in significant reductions in all predefined mortality end points including: total mortality, 45 versus 72 deaths (risk reduction 39%; 95% confidence interval 11% to 58%; p = 0.0086); sudden death, 22 vs. 39 deaths (45% [7% to 67%]; p = 0.024); and death due to worsening heart failure, 13 vs. 28 deaths (55% [13% to 77%]; p = 0.015). Metoprolol CR/XL also reduced the number of hospitalizations for worsening heart failure by 45% compared with placebo (p < 0.0001). The NYHA functional class improved in the metoprolol CR/XL group compared with placebo (p = 0.0031). Metoprolol CR/XL was well tolerated, with 31% fewer patients withdrawn from study medicine (all causes) compared with placebo (p = 0.027).
CONCLUSIONS
This subgroup analysis of the MERIT-HF study shows that patients with severe heart failure receive a similar mortality benefit and a similar reduction in hospitalizations for worsening heart failure with metoprolol CR/XL treatment as those patients included in the total study.
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Abbreviations and Acronyms
| | ACE | = angiotensin-converting enzyme | | BEST | = Beta-blocker Evaluation of Survival Trial | | CI | = confidence interval | | CIBIS II | = Cardiac Insufficiency Bisoprolol Study II | | COPERNICUS | = Carvedilol Prospective Randomized Cumulative Survival trial | | CR/XL | = controlled release/extended release | | MERIT-HF | = Metoprolol CR/XL Randomized Intervention Trial in chronic Heart Failure | | NYHA | = New York Heart Association |
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