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

What was known?

Prior myocardial infarction (MI) is strongly correlated with recurrent ischaemic events. The REDUCE_IT trial reported significant reductions in major ischemic events with newly-emerged icosapent ethyl (IPE). However, the specific impact of IPE among patients with prior MI and elevated triglycerides remains unidentified.


The aim of this sub-analysis of the REDUCE-IT trial was to examine the benefit of IPE ischaemic events among patients with prior MI and whether the degree of benefit is influenced by a history of revascularisation.

What this study adds:

These data emphasise the advantages of IPE and its considerable cardiovascular (CV) risk reduction in patients with established CV disease who have experienced a prior MI.

Clinical implications:

These data strongly support routine treatment with IPE in eligible patients with prior MI for significant CV risk reduction.

Study design:

The REDUCE-IT study (NCT01492361) was a phase 3b, randomised, double-blind, placebo-controlled trial that investigated the effects of IPE in reducing long-term CV events, in 8,179 statin-treated patients with mixed dyslipidaemia. Post hoc analyses of patients with prior MI and hypertriglyceridaemia were performed to evaluate the effect of IPE on ischemic events.

Primary endpoints:

  • CV death, MI, stroke, coronary revascularisation, or hospitalisation for unstable angina requiring hospitalisation

Secondary endpoints:

  • CV death, MI, or stroke

Inclusion criteria:

  • Men and non-pregnant or sterile women aged ≥ 45
  • Patients with hypertriglyceridemia and prior MI
  • Patients on statin therapy > 4 weeks
  • Established CV disease or at high risk for CV disease


  • A total of 3,693 patients were presented with a history of prior MI
  • Therapy with IPE vs placebo significantly decreased the incidence of the primary composite endpoint from 26.1% to 20.2% [hazard ratio (HR), 0.74; 95% confidence interval (CI), 0.650.85; p=0.00001]
  • The key secondary endpoint was decreased from 18.0% to 13.3% with IPE vs placebo (HR, 0.71; 95% CI, 0.61–0.84; p=0.00006):
    • 35% relative risk reduction (RRR) in total ischemic events (p= 0.0000001)
    • 34% in MI (p= 0.00009)
    • 30% in CV death (p= 0.01)
    • 20% in all-cause mortality (p= 0.054),
  • Similar reductions were observed in additional endpoints:
    • 34% RRR in fatal or nonfatal MI (p=0.00009)
    • 30% RRR in CV death (p=0.01), and a
    • nonsignificant 21% RRR in fatal or nonfatal stroke
    • absolute risk reductions of 3.7%, 1.9%, and 0.7% for fatal or nonfatal MI, CV death, and fatal or nonfatal stroke, respectively
  • IPE resulted in significant reductions in sudden cardiac death (40%) and cardiac arrest (56%)   


In the REDUCE-IT trial patients with prior MI who were treated with IPE exhibited significant risk reductions in first and total ischemic events, including CV death, sudden cardiac death, and cardiac arrest, but a slightly higher rate of atrial fibrillation.The benefits of IPE treatment in patients with previous MI were stable across subgroups, with or without a record of prior revascularisation. These effects were similar among patients with or without history of MI.


  • Data included both prespecified and post hoc analyses however, REDUCE-IT was not powered for subgroup analyses – making the results hypothesis-generating
  • Enrolment was not stratified by prior MI or time since MI
  • Patients were not enrolled at the time of their MI
  • No adjustments were made for multiple comparisons