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

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.

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.

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

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.

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

• CV death, MI, or stroke

• 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), 0.65–0.85; 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