- Question
- Does adding once-daily controlled/extended-release metoprolol (CR/XL) to optimal standard therapy lower mortality in patients with chronic heart failure and reduced ejection fraction?
- Design
- Double-blind, placebo-controlled randomized trial of 3991 patients, preceded by a 2-week single-blind placebo run-in. It was stopped early on the recommendation of the independent safety committee; mean follow-up was 1 year.
- Population
- Patients with chronic heart failure in NYHA functional class II-IV and an ejection fraction of 0.40 or less, stabilized on optimal standard therapy.
- Intervention
- Once-daily metoprolol CR/XL, started at 12.5 mg (NYHA III-IV) or 25.0 mg (NYHA II) and up-titrated over 8 weeks to a target dose of 200 mg daily (1990 patients).
- Control
- Placebo on top of standard therapy (2001 patients).
- Primary outcome
- All-cause mortality, analyzed by intention to treat.
- Results
- All-cause mortality was lower with metoprolol CR/XL than with placebo (145 deaths [7.2%] vs 217 [11.0%]; relative risk 0.66; 95% CI 0.53-0.81; p=0.00009, or p=0.0062 adjusted for interim analyses). There were also fewer sudden deaths (79 vs 132; 0.59 [0.45-0.78]).
- Conclusion
- Once-daily metoprolol CR/XL added to optimal standard therapy improved survival and was well tolerated.
- Why it matters
- It provided evidence that a specific beta-blocker reduces mortality in heart failure with reduced ejection fraction, supporting its place in the routine treatment of these patients.
Card generated automatically with AI from the abstract of the original publication and the trial registry; every figure was checked against those sources. It may contain errors: verify the data at the source before using it for clinical decisions.
Generated on October 7, 2026