REDUCE-AMI

Published

Yndigegn T, et al. "Beta-blockers after myocardial infarction and preserved ejection fraction". The New England Journal of Medicine. 2024. 390(15):1372-1381.
PubMed • Full text • PDF • ClinicalTrials.gov

Clinical Question

Among adults with an acute MI, does use of beta-blockers lower MI or all-cause mortality when compared to no beta-blockers?

Bottom Line

Among adults with an acute MI, use of beta-blockers does not lower MI or all-cause mortality when compared to no beta-blockers

Major Points

The use of beta-blockers has been a component of guideline recommended post-MI care. For example, the 2013 ACCF/AHA STEMI guidelines recommended use of beta-blockers post-MI discharge using class I LOE B. A 2021 Cochrane review determined that the evidence supported the use of beta-blockers to lower all-cause death and recurrent MI. However, the authors of this review noted that there were no trials determining the role of beta-blocker without LV dysfunction.

Published in 2024, the REDUCE-SWEDEHEART (termed "REDUCE-AMI" in its publication) trial randomized 5,020 patients in Sweden, Estonia, and New Zealand who had a STEMI or type 1 NSTEMI with a post-MI LVEF ≥50% as entered into the SWEDEHEART registry to either beta-blocker use or no beta-blocker use in an open-label design. There was no difference between groups in the proportion with recurrent MI or all-cause mortality (7.9% vs 8.3%). Ultimately, this trial provides some initial evidence that beta-blockers might not be indicated post-MI if there is preserved ejection fraction on a post-MI echocardiogram.

Guidelines

As of May 2024, no guidelines have been published that reflect the results of this trial.

Design

• Registry-based, prospective, open label RCT
• N=5,020
  • Beta-blockers (n=2,508)
  • No beta-blockers (n=2,512)
• Setting: 45 centers in Sweden, Estonia, and New Zealand
• Enrollment: 2017-2023
• Follow-up: Through 11/2023
• Analysis: Intention-to-treat
• Primary outcome: MI or all-cause mortality

Population

Inclusion Criteria

• Aged ≥18 years
• MI in prior week, with NSTEMI being specified as type 1 of the Fourth Universal Definition and included in the SWEDEHEART registry
• Angiography during hospitalization
• Obstructive coronary disease (stenosis ≥50%, FFR ≤0.80 or iFR ≤0.89)
• Post-MI EF ≥50%
• NOTE: Heart failure was not an eligibility criteria as this is not a HFpEF trial, it's an MI without ventricular dysfunction trial.

Exclusion Criteria

• Contraindications to beta-blocker use
• Indication for beta-blocker use

Baseline Characteristics

From the beta-blocker group.

• Demographics: Age 65y, female sex 22%, Sweden 95%, Estonia 0.6%, New Zealand 4%
• CVD risk factors: Smoking 19%, HTN 46%, DM 14%
• Prior CVD details: MI 7%, PCI 6%, CABG 1%, stroke 2%, HF 0.5%
• Presenting details: Chest pain 97%, CPR before arrival 0.4%, rales 1%, HR 74 BPM, SBP 150 mm Hg, AF 0.8%, on beta blockers 11%, days to randomization 2
• MI type: STEMI 25%
• Hospital care:
  • Angiography: No stenosis 1%, 1 vessel disease 56%, 2 vessel disease 27%, LM or 3 vessel disease 16%
  • PCI: 96%
  • CABG: 4%
• Discharge meds: ASA 98%, P2Y12 antagonist 96%, Beta-blocker 96% (vs 10% in other arm), ACE or ARB 79%, statin 99%, diuretic 8%, CCB 17%

Interventions

• Randomized to a group:
  • Beta-blocker - With preference of metoprolol over bisoprolol, medication started during hospitalization and continued post-discharge.
  • No beta-blocker - Discouraged from using a beta-blocker. For those on a beta-blocker prior to admission, tapering occurred over 2-4 weeks.
• BP control followed guidelines, and included avoidance of beta blocker use

Outcomes

Comparisons are beta-blocker vs. no beta-blocker.

Primary Outcome

Components of the primary outcome are secondary outcomes but are presented here for simplicity.

MI or all-cause mortality

7.9% vs 8.3% (HR 0.96; 95% CI 0.79 to 1.16; P=0.64)

All-cause mortality: 3.9% vs. 4.1% (HR 0.94; 95% CI 0.71 to 1.24)

CVD mortality: 15% vs. 1.3% (HR 1.15; 95% CI 0.72 to 1.84)

MI: 4.5% vs 4.7% (HR 0.96; 95% CI 0.74 to 1.24)

Secondary Outcomes

AF hospitalization

1.1% vs. 1.4% (HR 0.79; 95% CI 0.48 to 1.31)

HF hospitalization

0.8% vs. 0.9% (HR 0.91; 95% CI 0.50 to 1.66)

Subgroup Analysis

The subgroup analysis shown in Figure S10 in the supplementary appendix generally demonstrates similar effects of the intervention on the primary outcome when stratifying by pre-admission beta blocker status, heart rate, sex, age, hypertension status, diabetes status, prior MI, MI type, revascularization status, CKD status, AF status, and country.

Adverse Events

Hospitalization for bradycardia, 2nd or 3rd degree heart block, hypotension, syncope, or ICD/PPM placement

3.4% vs. 3.2% (HR 1.08; 95% CI 0.79 to 1.46)

Asthma or COPD hospitalization

0.6% vs. 0.6% (HR 0.94; 95% 0.46 to 1.89)

Stroke hospitalization

Difference in mean survival time shown, a post-hoc analysis.

1.4% vs. 1.8% (HR 6.80; 95% CI -7.11 to 20.72)

Criticisms

• Open label design.
• Event ascertainment used a registry, which might have misclassified some events.
• Limited ascertainment of complications. Specifically, there was no assessment of HF hospitalizations.

Funding

Public funding, including Swedish Research Council, Swedish Heart Lung Foundation, Stockholm County Council, Green Lane Research and Educational Fund, Swedish Heart Lung Foundation, Estonian Research Council, and Region Stockholm