Authors
The MERIT-HF Study Group
Title
Effect of metoprolol CR/XL in chronic heart failure: Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure
References
Lancet 1999;353:2001-07.
Background
At the time of initiation of this study, ACEi and diuretics were first line for treatment of left ventricular systolic heart failure, however high mortality rates continue to exist. In previous β-blocker trials where survival was not the primary endpoint, a decrease in mortality was demonstrated.
Purpose
To determine if metoprolol CR/XL, when added to optimal medication therapy positively affects survival outcomes in patients with decreased LVEF (≤40%) and symptoms of HF (NYHA Class II-IV).
Design
  • Randomized, double-blind, placebo controlled trial
  • 3991 stable patients, age 40-80 years, with NYHA class II-IV symptoms for at least 3 months, ejection fraction ≤40% within the past 3 months
  • receiving ≥2 weeks of optimum standard therapy: ACEi and diuretic (ARB, long acting nitrate or hydralazine if ACE inhibitor not tolerated), digitalis permitted
Exclusion Criteria
  • Acute MI or UA within 28 days
  • HF due to systemic disease or alcohol abuse
  • Unstable HF, SBP <100 mmHg
  • Already on or contraindications for β-blocker or medications with β-blockade (amiodarone); β-blocker use within 6 weeks, as well as calcium antagonists or amiodarone use within 6 months
  • 2° or 3° AV block; unstable decompensated heart failure
  • recent/planned heart transplant, ICD, CABG, PCI
  • any other clinically significant, coexisting condition
Follow-Up
Mean of 1 year (stopped prematurely, prespecified criteria met)
Treatment Regimen
  • metoprolol CR/XL 12.5 or 25 mg once daily (12.5 mg recommended for NYHA III-IV patients) x 2 weeks, then doubled every two weeks up to target of 200 mg once daily at investigator’s discretion and patient tolerability
Results

Meto-
prolol CR/XL
n=1990		Placebo
n=2001		Relative Riskp
All cause mortality (per patient yr)
7.2%10.8%0.66 (0.53-0.81)0.00009*
CV death
6.4%10.1%0.62 (0.50-0.78)0.00003
Sudden death
4%6.6%0.59 (0.45-0.78)0.0002
HF death
1.5%2.9%0.51 (0.33-0.79)0.0023
* p=0.0062 when adjusted for interim analyses
Summary
The addition of metoprolol CR/XL in patients with systolic heart failure, optimal medications and NYHA class II – IV symptoms, increases survival rates and reduces mortality rates from cardiovascular causes, heart failure causes and sudden death.