Effect of metoprolol CR/XL in chronic heart failure: Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure (MERIT-HF)

Lancet. 1999 Jun 12;353(9169):2001-7.

Abstract

Background: Metoprolol can improve haemodynamics in chronic heart failure, but survival benefit has not been proven. We investigated whether metoprolol controlled release/extended release (CR/XL) once daily, in addition to standard therapy, would lower mortality in patients with decreased ejection fraction and symptoms of heart failure.

Methods: We enrolled 3991 patients with chronic heart failure in New York Heart Association (NYHA) functional class II-IV and with ejection fraction of 0.40 or less, stabilised with optimum standard therapy, in a double-blind randomised controlled study. Randomisation was preceded by a 2-week single-blind placebo run-in period. 1990 patients were randomly assigned metoprolol CR/XL 12.5 mg (NYHA III-IV) or 25.0 mg once daily (NYHA II) and 2001 were assigned placebo. The target dose was 200 mg once daily and doses were up-titrated over 8 weeks. Our primary endpoint was all-cause mortality, analysed by intention to treat.

Findings: The study was stopped early on the recommendation of the independent safety committee. Mean follow-up time was 1 year. All-cause mortality was lower in the metoprolol CR/XL group than in the placebo group (145 [7.2%, per patient-year of follow-up]) vs 217 deaths [11.0%], relative risk 0.66 [95% CI 0.53-0.81]; p=0.00009 or adjusted for interim analyses p=0.0062). There were fewer sudden deaths in the metoprolol CR/XL group than in the placebo group (79 vs 132, 0.59 [0.45-0.78]; p=0.0002) and deaths from worsening heart failure (30 vs 58, 0.51 [0.33-0.79]; p=0.0023).

Interpretation: Metoprolol CR/XL once daily in addition to optimum standard therapy improved survival. The drug was well tolerated.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic beta-Antagonists / therapeutic use*
  • Adult
  • Aged
  • Aged, 80 and over
  • Cardiovascular Diseases / mortality
  • Death, Sudden
  • Delayed-Action Preparations
  • Double-Blind Method
  • Female
  • Heart Failure / drug therapy*
  • Heart Failure / mortality
  • Humans
  • Male
  • Metoprolol / therapeutic use*
  • Middle Aged
  • Survival Rate

Substances

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