Historical collection · First published Nov 17, 2024; added to EM Weekly Oct 28, 2026. This retrospective summary may be superseded by later evidence or guidance.
← All articlesRoutine Spironolactone in Acute Myocardial Infarction
Summary
In the companion CLEAR SYNERGY comparison, 7,062 post-PCI MI patients at 104 centers in 14 countries were randomized to routine spironolactone or placebo in a blinded 2-by-2 factorial trial. Cardiovascular death or new/worsening heart failure totaled 183 versus 220 events (1.7 vs 2.1 per 100 patient-years; competing-risk-adjusted HR 0.91, 95% CI 0.69–1.21; P=0.51), and the second coprimary composite occurred in 7.9% versus 8.3% (HR 0.96, 95% CI 0.81–1.13; P=0.60). Serious adverse events occurred in 7.2% versus 6.8%.
Why it matters
Routine addition of spironolactone to a broad contemporary post-MI population did not improve the trial's coprimary outcomes. This argues against blanket MRA initiation after every MI, while leaving intact the established targeted indication for ACS patients with reduced LVEF plus heart-failure symptoms and/or diabetes.
Study at a glance
- Design
- Randomized trial
- Population
- Adults with acute myocardial infarction who had undergone percutaneous coronary intervention at 104 centers in 14 countries.
- Sample size
- 7062
- Intervention
- Spironolactone 25 mg once daily versus matching placebo, with independent colchicine/placebo allocation in the factorial design.
- Comparator
- Matching placebo.
- Primary endpoint
- Two coprimary outcomes: total cardiovascular death or new/worsening heart-failure events; and first occurrence of MI, stroke, new/worsening heart failure, or cardiovascular death.
Main findings
- Total cardiovascular-death or new/worsening-HF events: 183 with spironolactone versus 220 with placebo, 1.7 versus 2.1 per 100 patient-years; adjusted HR 0.91 (95% CI 0.69–1.21), P=0.51.
- Second coprimary outcome: 280/3,537 (7.9%) versus 294/3,525 (8.3%); adjusted HR 0.96 (95% CI 0.81–1.13), P=0.60.
- Serious adverse events: 255/3,537 (7.2%) versus 241/3,525 (6.8%).
Limitations
The trial tested routine spironolactone in a broad post-PCI MI population, not specifically the high-risk subgroup with LVEF ≤40% plus heart-failure symptoms and/or diabetes for whom MRA therapy remains guideline-indicated. Its long-term outcomes are more relevant to inpatient/discharge planning than to an immediate ED intervention.
Read the primary source
Full text: Open-access full text available.
Original sourcePMID: 39555814
Material reviewed: abstract.
Source retrieved Oct 28, 2026. Historical backfill. NEJM publisher metadata and PubMed verify online publication on 2024-11-17, DOI 10.1056/NEJMoa2405923, PMID 39555814, and free-article availability. The publisher abstract plus official trial-registry dosing metadata were reviewed; this record does not claim end-to-end full-text review. Targeted title/DOI checking found no correction or retraction. Later 2025 ACC/AHA/ACEP/NAEMSP/SCAI ACS guidance retains a Class 1, LOE B-R MRA indication for ACS with LVEF ≤40% plus HF symptoms and/or diabetes, so CLEAR's neutral broad-population result is not presented as overturning that targeted indication.
Corrections & review history
No corrections recorded. Human review: not yet human-reviewed.