CLINICAL STUDY
Dose of metoprolol CR/XL and clinical outcomes in patients with heart failure
Analysis of the experience in metoprolol CR/XL randomized intervention trial in chronic heart failure (MERIT-HF)
John Wikstrand, MD, PhD*,*,1,
Å. ke Hjalmarson, MD, PhD ,
Finn Waagstein, MD, PhD,
B. jörn Fagerberg, MD, PhD*,
Sidney Goldstein, MD ,
John Kjekshus, MD, PhD ,
Hans Wedel, PhD|| MERIT-HF Study Group
* Wallenberg Laboratory for Cardiovascular Research, Sahlgrenska University Hospital, Göteborg, Sweden
Department of Cardiology, Sahlgrenska University Hospital, Göteborg, Sweden
Henry Ford Heart and Vascular Institute, Henry Ford Hospital, Detroit, Michigan, USA
Section of Cardiology, Rikshospitalet, Oslo, Norway
|| Nordic School of Public Health, Göteborg, Sweden
Manuscript received December 28, 2001;
revised manuscript received April 8, 2002,
accepted April 30, 2002.
* Reprint requests and correspondence: Dr. John Wikstrand, Wallenberg Laboratory, Sahlgrenska University Hospital, SE 413 45 Göteborg, Sweden.
john.wikstrand{at}wlab.gu.se
OBJECTIVES: We performed a post-hoc subgroup analysis in the Metoprolol CR/XL Randomized Intervention Trial in Chronic Heart Failure (MERIT-HF) with the aim of reporting on the heart rate (HR) response during the titration phase and clinical outcomes from the three-month follow-up visit to end of study in two dosage subgroups: one that had reached more than 100 mg of metoprolol CR/XL once daily (high-dose group; n = 1,202; mean 192 mg) and one that had reached 100 mg or less (low-dose group; n = 412; mean 76 mg).
BACKGROUND: Clinicians have questioned whether patients need to reach the target beta-blocker dose to receive benefit.
METHODS: Outcome (Cox-adjusted) was compared with all placebo patients with dose available at the three-month visit (n = 1,845).
RESULTS: Data indicated somewhat higher risk in the low-dose group compared with the high-dose group. Heart rate was reduced to a similar degree in the two dose groups, indicating higher sensitivity for beta-blockade in the low-dose group. The reduction in total mortality with metoprolol CR/XL compared with placebo was similar: 38% (95% confidence interval [CI], 16 to 55) in high-dose group (p = 0.0022) and also 38% (95% CI, 11 to 57) in the low-dose group (p = 0.010).
CONCLUSIONS: Risk reduction was similar in the high- and low-dose subgroups, which, at least partly, may be the result of similar beta-blockade as judged from the HR response. The results support the idea of an individualized dose-titration regimen, which is guided by patient tolerability and the HR response. Further research is needed to shed light on why some patients respond with a marked HR reduction and reduced mortality risk on a relatively small dose of a beta-blocker.
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Abbreviations and Acronyms
| | CI | | confidence interval | | CIBIS II | | Cardiac Insufficiency Bisoprolol Study | | COPERNICUS | | Carvedilol Prospective Randomized Cumulative Survival study | | CR/XL | | controlled-release/extended-release | | HF | | heart failure | | HR | | heart rate | | MERIT-HF | | Metoprolol CR/XL Randomized Intervention Trial in Chronic Heart Failure | | NYHA | | New York Heart Association |
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