What was the design, patient population, and primary findings of the REDUCE‑AMI trial evaluating long‑term metoprolol succinate after acute coronary syndrome?

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What is the REDUCE-AMI Trial?

The REDUCE-AMI trial was a landmark open-label randomized controlled trial that demonstrated long-term beta-blocker therapy (metoprolol or bisoprolol) provides no benefit over no beta-blocker treatment in patients with acute myocardial infarction who have preserved left ventricular ejection fraction (≥50%) and underwent early coronary angiography. 1

Trial Design

REDUCE-AMI was a parallel-group, open-label trial conducted at 45 centers across Sweden, Estonia, and New Zealand (95.4% of patients from Sweden). The study enrolled patients from September 2017 through May 2023. 1

Key inclusion criteria:

  • Acute myocardial infarction
  • Underwent coronary angiography
  • Left ventricular ejection fraction ≥50%
  • No other indications for beta-blocker therapy

Intervention arms:

  • Beta-blocker group: Long-term metoprolol or bisoprolol
  • Control group: No beta-blocker treatment

Patient Population

A total of 5,020 patients were randomized:

  • 2,508 patients assigned to beta-blocker therapy
  • 2,512 patients assigned to no beta-blocker therapy
  • Median follow-up: 3.5 years (interquartile range 2.2 to 4.7 years) 1

Primary Findings

The trial showed no benefit of beta-blocker therapy:

Primary endpoint (composite of death from any cause or new myocardial infarction):

  • Beta-blocker group: 7.9% (199/2,508 patients)
  • No beta-blocker group: 8.3% (208/2,512 patients)
  • Hazard ratio: 0.96 (95% CI 0.79-1.16; P=0.64) 1

Secondary endpoints also showed no benefit:

  • All-cause mortality: 3.9% vs 4.1%
  • Cardiovascular death: 1.5% vs 1.3%
  • Myocardial infarction: 4.5% vs 4.7%
  • Hospitalization for atrial fibrillation: 1.1% vs 1.4%
  • Hospitalization for heart failure: 0.8% vs 0.9% 1

Safety endpoints were similar between groups:

  • Hospitalization for bradycardia, AV block, hypotension, syncope, or pacemaker: 3.4% vs 3.2%
  • Hospitalization for asthma/COPD: 0.6% vs 0.6%
  • Hospitalization for stroke: 1.4% vs 1.8% 1

Clinical Context and Implications

This trial challenges decades of routine beta-blocker use after myocardial infarction. The historical benefit of beta-blockers was established in the pre-reperfusion era with large myocardial infarctions, before modern biomarker-based diagnosis, percutaneous coronary intervention, dual antiplatelet therapy, high-intensity statins, and RAAS antagonists. 1

The 2025 ACC/AHA/ACEP/NAEMSP/SCAI guidelines acknowledge this evolving evidence, noting that "an open-label randomized trial has raised questions about the benefit of long-term beta-blocker therapy following hospital discharge in patients with ACS who have undergone coronary revascularization and have preserved left ventricular function," and state "this area remains under study." 2

Important caveats:

  • The benefit of beta-blockers in patients with LVEF ≤40% remains undisputed and is strongly recommended 2
  • Early beta-blocker therapy (<24 hours) is still recommended to reduce reinfarction and ventricular arrhythmias during the acute phase 3, 2
  • The trial specifically excluded patients with other indications for beta-blockers (heart failure, reduced LVEF, arrhythmias)

A 2025 meta-analysis of 17,801 patients from five trials (including REDUCE-AMI) confirmed these findings, showing no benefit of beta-blockers in post-MI patients with LVEF ≥50% (HR 0.97; 95% CI 0.87-1.07; P=0.54). 4

References

4
Research

Beta-Blockers after Myocardial Infarction with Normal Ejection Fraction.

The New England journal of medicine, 2025

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Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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