Prevention of Cardiovascular Events and Mortality With Icosapent Ethyl in Patients With Prior Myocardial Infarction

J Am Coll Cardiol. 2022 May 3;79(17):1660-1671. doi: 10.1016/j.jacc.2022.02.035.


Background: REDUCE-IT was a double-blind trial that randomized 8,179 statin-treated patients with controlled low-density lipoprotein cholesterol and moderately elevated triglycerides to icosapent ethyl (IPE) or placebo. There was a significant reduction in the primary endpoint, including death from cardiovascular (CV) causes. The specific impact of IPE among patients with prior myocardial infarction (MI) was unknown.

Objectives: Our goal was to examine the benefit of IPE on ischemic events among patients with prior MI in REDUCE-IT.

Methods: We performed post hoc analyses of patients with prior MI. The primary endpoint was CV death, MI, stroke, coronary revascularization, or hospitalization for unstable angina. The key secondary endpoint was CV death, MI, or stroke.

Results: A total of 3,693 patients had a history of prior MI. The primary endpoint was reduced from 26.1% to 20.2% with IPE vs placebo; HR: 0.74 (95% CI: 0.65-0.85; P = 0.00001). The key secondary endpoint was reduced from 18.0% to 13.3%; HR: 0.71 (95% CI: 0.61-0.84; P = 0.00006). There was also a significant 35% relative risk reduction in total ischemic events (P = 0.0000001), a 34% reduction in MI (P = 0.00009), a 30% reduction in CV death (P = 0.01), and a 20% lower rate of all-cause mortality (P = 0.054), although there was a slight increase in atrial fibrillation. Sudden cardiac death and cardiac arrest were also significantly reduced by 40% and 56%, respectively.

Conclusions: Patients with a history of prior MI in REDUCE-IT treated with IPE demonstrated large and significant relative and absolute risk reductions in ischemic events, including CV death. (A Study of AMR101 to Evaluate Its Ability to Reduce Cardiovascular Events in High Risk Patients With Hypertriglyceridemia and on Statin. The Primary Objective is to Evaluate the Effect of 4 g/Day AMR101 for Preventing the Occurrence of a First Major Cardiovascular Event. [REDUCE-IT]; NCT01492361).

Keywords: clinical trials; icosapent ethyl; ischemic events; myocardial infarction.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Eicosapentaenoic Acid / analogs & derivatives
  • Eicosapentaenoic Acid / therapeutic use
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors* / therapeutic use
  • Hypertriglyceridemia* / drug therapy
  • Myocardial Infarction* / drug therapy
  • Myocardial Infarction* / epidemiology
  • Myocardial Infarction* / prevention & control
  • Stroke*


  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • eicosapentaenoic acid ethyl ester
  • Eicosapentaenoic Acid

Associated data