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Randomized Evaluation of Decreased Usage of Beta-Blockers After Acute Myocardial Infarction - REDUCE-AMI
Highlighted text has been updated as of Nov. 9, 2025.
Contribution To Literature:
The REDUCE-AMI trial showed that in patients with acute myocardial infarction (AMI) and preserved left ventricular ejection fraction (LVEF), beta-blockade with metoprolol or bisoprolol was not associated with decreased all-cause mortality or future acute myocardial infarction (AMI) compared with usual care.
Study Design
- Registry-based
- International, multicenter
- Randomized
- Open-label
Patients with AMI without reduced LVEF were randomized in a 1:1 fashion to receive beta-blockade (n = 2,508) with oral metoprolol or bisoprolol titrated to a target dose ≥100 mg daily or ≥5 mg daily, respectively, or to usual care (n = 2,512). Beta-blockade was initiated inpatient and continued after discharge. Patients in the usual care arm who were already on a beta-blocker were tapered off over 2-4 weeks.
- Total number of enrollees: 5,020
- Median duration of follow-up: 3.5 years
- Median patient age: 65 years
- Percentage female: 23%
Inclusion criteria:
- Age ≥18 years
- Type I ST-elevation or NSTE-MI ≤7 days prior
- Coronary angiography performed during index hospitalization
- Obstructive coronary artery disease (stenosis ≥50% or positive invasive physiologic testing in any vessel) on coronary angiography at or any time before index hospitalization
- Echocardiographic LVEF ≥50%
Exclusion criteria:
- Contraindication for beta-blockade
- Alternative indication for beta-blockade
Other salient features/characteristics:
- STEMI: 35%
- On chronic beta-blocker therapy at randomization: 12%
- Left main or three-vessel disease: 17%
- PCI: 96%
- CABG: 4%
Principal Findings:
The primary outcome, composite of all-cause death or nonfatal AMI, for beta-blockade vs. usual care, was: 7.9% vs. 8.3%, hazard ratio (HR) 0.96 (95% confidence interval [CI] 0.79-1.16), p = 0.64.
Secondary outcomes for beta-blockade vs. usual care:
- All-cause death: 3.9% vs. 4.1%, HR 0.94 (95% CI 0.71-1.24), p = 0.66
- AMI: 4.5% vs. 4.7%, HR 0.96 (95% CI 0.74-1.24), p = 0.74
- Heart failure (HF) hospitalization: 0.8% vs. 0.9%, HR 0.91 (95% CI 0.50-1.66), p = 0.76
Safety outcomes for beta-blockade vs. usual care:
- Hospitalization for bradyarrhythmia, hypotension, or syncope: 3.4% vs. 3.2%, HR 1.08 (95% CI 0.79-1.46), p = 0.64
- Asthma/COPD hospitalization: 0.6% vs. 0.6%, HR 0.94 (95% CI 0.46-1.89), p = 0.86
- Stroke hospitalization: 1.4% vs. 1.8%, HR 0.78 (95% CI 0.51-1.21), p = 0.35
Beta-blocker adherence:
- Beta-blockade arm: 90.6% at 6-10 weeks and 81.9% at 11-13 months
- Usual care arm: 11.3% at 6-10 weeks and 14.3% at 11-13 months
Beta-blocker meta-analysis:
REDUCE-AMI was one of five clinical trials included in a meta-analysis (REBOOT, REDUCE-AMI, BETAMI, DANBLOCK, and CAPITAL-RCT) of patients with a preserved LVEF (≥50%) after recent MI. One half of the patients were assigned to a beta-blocker and half to no beta-blocker.
Results showed that during a 3.6-year follow-up, a primary endpoint event (all-cause death, MI, or HF) occurred in 8.1% in the beta-blocker group and 8.3% in the no beta-blocker group (hazard ratio [HR], 0.97; 95% CI, 0.87-1.07; p=0.54). For patients in the beta-blocker vs. no beta-blocker groups, respectively: all-cause death occurred in 3.8% vs. 3.6% (HR, 1.04); MI occurred in 4.1% vs. 4.5% (HR, 0.89); and HF occurred in 0.8% vs. 1.0% (HR, 0.87).
Interpretation:
The clinical benefit of beta-blockade in post-AMI management, particularly without reduced LVEF, has become less clear with advances in early revascularization and optimal medical therapy. REDUCE-AMI represents the first modern, randomized data of beta-blocker therapy in this population and found no association with reduced all-cause mortality or recurrent AMI.
There was significant crossover between groups at 1 year, and medication adherence could not be assessed beyond that point. Coupled with the slightly lower than anticipated event rate, this may have affected results over longer follow-up. The increased beta-blocker use in the usual care arm over time may reflect treatment of common comorbidities following AMI, including stable angina, atrial fibrillation, hypertension, or subsequent reduced LVEF.
Assessment of endpoints was limited to registry-collected data, limiting evaluation for such related cardiovascular events in this cohort. There were no adverse safety signals in the treatment arm. Patients with preserved LVEF following AMI, therefore, may not derive significant cardiac benefit from beta-blockers without another indication for their use.
A meta-analysis of individual-level data from patients with preserved LVEF (≥50%) after MI in five randomized trials, including REDUCE-AMI, showed that treatment with beta-blocker therapy did not reduce the incidence of all-cause death, MI, or HF. These findings differ from a meta-analysis of patients with reduced LVEF (40-49%), which showed a 25% relative reduction in the composite of all-cause death, MI, or HF. The authors point out that LVEF is a strong prognostic factor in patients with MI and HF, which may explain why beta-blockers in this population with preserved LVEF were "less relevant."
References:
Presented by Anna Meta Dyrvig Kristensen, MD, at the American Heart Association Scientific Sessions (AHA 2025), New Orleans, LA, Nov. 9, 2025.
Yndigegn T, Lindahl B, Mars K, et al. Beta-Blockers After Myocardial Infarction and Preserved Ejection Fraction. N Engl J Med 2024;390:1372-81.
Editorial: Steg PG. Routine Beta-Blockers in Secondary Prevention — On Injured Reserve. N Engl J Med 2024;390:1434-6.
Presented by Dr. Troels Yndigegn at the American College of Cardiology Annual Scientific Session (ACC.24), Atlanta, GA, April 7, 2024.
Clinical Topics: Acute Coronary Syndromes
Keywords: ACC24, ACC Annual Scientific Session, Myocardial Infarction, Novel Agents, AHA Annual Scientific Sessions, AHA25
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