Randomized Evaluation of Decreased Usage of Beta-Blockers After Acute Myocardial Infarction - REDUCE-AMI

Apr 07, 2024
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Author/Summarized by Author:
Amit Saha, MD
Summary Reviewer:
Anthony A. Bavry, MD,MPH,FACC
Trial Sponsor:
Swedish Research Council and others
Date Presented:
04/07/2024
Date Published:
04/07/2024
Original Posted Date:
04/07/2024
References

Contribution To Literature:

The REDUCE-AMI trial showed that in patients with AMI and preserved LVEF, beta-blockade with metoprolol or bisoprolol was not associated with decreased all-cause mortality or future AMI compared with usual care.

Description:

The goal of the trial was to evaluate the potential benefit of beta-blockade following acute myocardial infarction (AMI) in patients with preserved left ventricular ejection fraction (LVEF) in the modern era of coronary revascularization and medical therapy.

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 non-ST elevation 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%
  • Percutaneous coronary intervention: 96%
  • Coronary artery bypass grafting: 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

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.

References:

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


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