Effects of controlled-release metoprolol on total mortality, hospitalizations, and well-being in patients with heart failure: the Metoprolol CR/XL Randomized Intervention Trial in congestive heart failure (MERIT-HF). MERIT-HF Study Group.

Abstract

CONTEXT:

Results from recent studies on the effects of beta1-blockade in patients with heart failure demonstrated a 34% reduction in total mortality. However, the effect of beta1-blockade on the frequency of hospitalizations, symptoms, and quality of life in patients with heart failure has not been fully explored.

OBJECTIVE:

To examine the effects of the beta1-blocker controlled-release/extended-release metoprolol succinate (metoprolol CR/XL) on mortality, hospitalization, symptoms, and quality of life in patients with heart failure.

DESIGN:

Randomized, double-blind controlled trial, preceded by a 2-week single-blind placebo run-in period, conducted from February 14, 1997, to October 31, 1998, with a mean follow-up of 1 year.

SETTING:

Three hundred thirteen sites in 14 countries.

PARTICIPANTS:

Patients (n = 3991) with chronic heart failure, New York Heart Association (NYHA) functional class II to IV, and ejection fraction of 0.40 or less who were stabilized with optimum standard therapy.

INTERVENTIONS:

Patients were randomized to metoprolol CR/XL, 25 mg once per day (NYHA class II), or 12.5 mg once per day (NYHA class III or IV), titrated for 6 to 8 weeks up to a target dosage of 200 mg once per day (n = 1990); or matching placebo (n = 2001).

MAIN OUTCOME MEASURES:

Total mortality or any hospitalization (time to first event), number of hospitalizations for worsening heart failure, and change in NYHA class, by intervention group; quality of life was assessed in a substudy of 741 patients.

RESULTS:

The incidence of all predefined end points was lower in the metoprolol CR/XL group than in the placebo group, including total mortality or all-cause hospitalizations (the prespecified second primary end point; 641 vs 767 events; risk reduction, 19%; 95% confidence interval [CI], 10%-27%; P<.001); total mortality or hospitalizations due to worsening heart failure (311 vs 439 events; risk reduction, 31%; 95% CI, 20%-40%; P<.001), number of hospitalizations due to worsening heart failure (317 vs 451; P<.001); and number of days in hospital due to worsening heart failure (3401 vs 5303 days; P<.001). NYHA functional class, assessed by physicians, and McMaster Overall Treatment Evaluation score, assessed by patients, both improved in the metoprolol CR/XL group compared with the placebo group (P = .003 and P = .009, respectively).

CONCLUSIONS:

In this study of patients with symptomatic heartfailure, metoprolol CR/XL improved survival, reduced the need for hospitalizations due to worsening heart failure, improved NYHA functional class, and had beneficial effects on patient well-being.

• Authors: A Hjalmarson, S Goldstein, B Fagerberg, H Wedel, F Waagstein, J Kjekshus, J Wikstrand, D El Allaf, J Vítovec, J Aldershvile, M Halinen, R Dietz, K L Neuhaus, A Jánosi, G Thorgeirsson, P H Dunselman, L Gullestad, J Kuch, J Herlitz, P Rickenbacher, S Ball, S Gottlieb, P Deedwania
• Journal: JAMA (JAMA) Vol. 283 Issue 10 Pg. 1295-302 (Mar 08 2000) ISSN: 0098-7484 [Print] United States
• PMID: 10714728 (Publication Type: Clinical Trial, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Adrenergic beta-Antagonists
• Delayed-Action Preparations
• Metoprolol

Topics

• Adrenergic beta-Antagonists (administration & dosage, therapeutic use)
• Delayed-Action Preparations
• Double-Blind Method
• Female
• Heart Failure (drug therapy, mortality, physiopathology)
• Hospitalization (statistics & numerical data)
• Humans
• Male
• Metoprolol (administration & dosage, analogs & derivatives, therapeutic use)
• Middle Aged
• Proportional Hazards Models
• Quality of Life
• Survival Analysis
• Treatment Outcome