Individual participant data analysis of two trials on aldosterone blockade in myocardial infarction

Heart. 2018 Nov;104(22):1843-1849. doi: 10.1136/heartjnl-2018-312950. Epub 2018 Apr 25.

Abstract

Background: Two recent randomised trials studied the benefit of mineralocorticoid receptor antagonists (MRAs) in ST-segment elevation myocardial infarction (STEMI) irrespective or in absence of heart failure. The studies were both undersized to assess hard clinical endpoints. A pooled analysis was preplanned by the steering committees.

Methods: We conducted a prespecified meta-analysis of patient-level data of patients with STEMI recruited in two multicentre superiority trials, randomised within 72 hours after symptom onset. Patients were allocated (1:1) to two MRA regimens: (1) an intravenous bolus of potassium canrenoate (200 mg) followed by oral spironolactone (25 mg once daily) versus standard therapy or (2) oral eplerenone (25-50 mg) versus placebo. The primary and key secondary outcomes, all-cause death and the composite of all-cause death or resuscitated sudden death, respectively, were assessed in the intention-to-treat population using a Cox model stratified on the study identifier.

Results: Patients were randomly assigned to receive (n=1118) or not the MRA regimen (n=1123). After a median follow-up time of 188 days, the primary and secondary outcomes occurred in 5 (0.4%) and 17 (1.5%) patients (adjusted HR (adjHR) 0.31, 95% CI 0.11 to 0.86, p=0.03) and 6 (0.5%) and 22 (2%) patients (adjHR 0.26, 95% CI 0.10 to 0.65, p=0.004) in the MRA and control groups, respectively. There were also trends towards lower rates of cardiovascular death (p=0.06) and ventricular fibrillation (p=0.08) in the MRA group.

Conclusion: Our analysis suggests that compared with standard therapy, MRA regimens are associated with a reduction of death and death or resuscitated sudden death in STEMI.

Keywords: acute myocardial infarction.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Canrenoic Acid / administration & dosage*
  • Canrenoic Acid / adverse effects
  • Eplerenone / administration & dosage*
  • Eplerenone / adverse effects
  • Equivalence Trials as Topic
  • Female
  • Humans
  • Male
  • Middle Aged
  • Mineralocorticoid Receptor Antagonists / administration & dosage*
  • Mineralocorticoid Receptor Antagonists / adverse effects
  • Multicenter Studies as Topic
  • Risk Factors
  • ST Elevation Myocardial Infarction / diagnosis
  • ST Elevation Myocardial Infarction / drug therapy*
  • ST Elevation Myocardial Infarction / mortality
  • ST Elevation Myocardial Infarction / physiopathology
  • Spironolactone / administration & dosage*
  • Spironolactone / adverse effects
  • Time Factors
  • Treatment Outcome

Substances

  • Mineralocorticoid Receptor Antagonists
  • Spironolactone
  • Eplerenone
  • Canrenoic Acid