Metoprolol versus placebo on the impact of mortality with patients with NYHA class II-IV and left ventricular ejection fraction ≤ 40%
Topic: Beta-blockers in heart failure with reduced ejection fraction
Aim:
- To investigate whether metoprolol controlled release/extended release once daily added to optimum standard therapy lowers mortality in patients with decreased ejection fraction < 40% and symptoms of heart failure
Design:
- Multi-centered, double blinded, randomized control trial
Treatment:
- Initial: Metoprolol 12.5 mg (if in NYHA class III-IV) or 25 mg daily
- Target: Metoprolol 200 mg daily
Control:
- Placebo
Cohort:
- 3,991 patients
Inclusion criteria:
- Aged 40-80 years
- NYHA II-IV for 3 months or more before enrollment
- Receiving standard medical therapy with diuretics and ACE-I
- Stable for 2 weeks prior to enrollment
- Left ventricular ejection fraction ≤ 40% within 3 months before enrollment
Exclusion criteria:
- Beta-blocker therapy within 6 months before enrollment
- AMI or USA within 1 month of randomization
- Heart failure due to systemic disease or alcohol abuse
- Scheduled or performed heart transplantation or cardiomyopathy
- Implanted cardioversion defibrillator
- CABG or PCI within 4 months of enrollment
- Unstable decompensated heart failure
- Supine systolic blood pressure < 100 mm Hg
- Use of diltiazem or verapamil
- Use of amiodarone within 6 months before enrollment
Follow up:
- 1 year
Primary endpoint:
- Death
- CV death
- Death from heart failure
- Heart failure symptoms
- Confinement to bed because of heart failure
- Sudden death
Main results:
- All cause mortality lower in metoprolol XR group: 7.2% vs 11.0 %, p = 0.0062
- Fewer deaths in the metoprolol XR group than in the placebo group (79 vs 132, p = 0.0002) and deaths from worsening HF (30 vs 58, p = 0.0023)
TAKE AWAY: Metoprolol XR once daily in addition to optimum standard therapy improved survival. The drug was well tolerated.
