Icosapent ethyl reduces ischemic events in patients with recent ACS


In a post hoc analysis of REDUCE-IT, icosapent ethyl lowered the risk of first and total ischemic events in patients with recent ACS, without increasing rates of bleeding.

This summary is based on the publication of Sayah N, Bhatt DL, Miller M, et al. - Icosapent ethyl following acute coronary syndrome: the REDUCE-IT trial. Eur Heart J. 2024 Jan 22:ehad889. doi: 10.1093/eurheartj/ehad889

Introduction and methods


The REDUCE-IT trial demonstrated that icosapent ethyl (IPE) reduces ischemic events compared with placebo in patients with elevated triglyceride levels [1]. On the other hand, it also showed that treatment with IPE was associated with increased rates of bleeding and AF compared with placebo [1]. These results were later confirmed in patients with prior MI [2]. Patients with recent ACS often receive antithrombotic therapy, which may increase bleeding risk with IPE. It remains unclear how IPE affects clinical outcomes and safety in patients with recent (<12 months) ACS.

Aim of the study

The aim of this post hoc analysis of REDUCE-IT was to determine the benefit and safety of IPE in patients with recent ACS.


The REDUCE-IT trial was a double-blind, placebo-controlled trial in which 8179 statin-treated patients with controlled LDL-c (41-100 mg/dL (1.06-2.59 mmol/L)) and moderately elevated triglycerides (150-499 mg/dL (1.69-5.63 mmol/L)), and with either established CVD or with diabetes and at least one additional risk factor, were randomized to either IPE 4g/day or placebo. Recent ACS was defined as MI or unstable angina within 12 months before randomization. A total of 840 patients in REDUCE-IT experienced a recent ACS (median age 59,5 years, 76.9% men), of which 805 (95.8%) received antiplatelet therapy, 584 (69.5%) received dual antiplatelet therapy (DAPT), 54 (6.4%) were on oral anticoagulant therapy, and 39 (4.6%) were on anticoagulant plus antiplatelet therapy. Median follow-up period was 4.75 years.


The primary outcome was a composite of cardiovascular death, non-fatal MI, non-fatal stroke, coronary revascularization or hospitalization for unstable angina.

Main results

Clinical outcomes

  • Compared with placebo, IPE reduced the risk of the first primary composite outcome in patients with recent ACS (HR: 0.63; 95%CI: 0.48-0.84; P=0.002; absolute risk reduction: 9.3%; number needed to treat [NNT]: 11).
  • IPE also reduced the incidence of total primary composite outcomes (i.e., first and subsequent events) compared with placebo in patients with recent ACS (relative risk: 0.64; 95%CI: -0.45-0.90; P=0.01).
  • In patients with ACS ≥12 months before randomization, IPE also reduced the risk of the first primary outcome compared with placebo (HR: 0.78; 95%CI: 0.68-0.90; P=0.0004; NNT: 21), albeit to a lesser extent compared to patients with ACS<12 months before randomization.

Safety outcomes

  • There was no difference in total bleeding or bleeding-related serious adverse events between the IPE group and the placebo group (incidence of 6.9% vs. 8.1%; Fisher’s exact P=0.60; and 1.6% vs. 3.2%; Fisher’s exact P=0.17; respectively).
  • Among patients with recent ACS who were on DAPT, at least one treatment-emergent bleeding adverse event occurred in 7.7% of patients in the IPE group and in 9.4% of patients in the placebo group (Fisher’s exact P=0.46).
  • There were no reports of hemorrhagic stroke in either treatment group.
  • Treatment-emergent adverse event of AF or flutter occurred more often in the IPE group compared with the placebo group (7.4% vs. 2.9%; Fisher's exact P=0.005), as well as hospitalization for AF or flutter (4.8% vs. 1.7%; log-rank P=0.01).


In this post hoc analysis of the REDUCE-IT trial, IPE reduced the risk of first and total primary composite outcomes in patients with recent ACS compared with placebo. Treatment with IPE in patients with recent ACS was associated with increased rates of AF or flutter, but not with increased rates of bleeding.


1. Bhatt DL, Steg PG, Miller M, et al. Cardiovascular risk reduction with icosapent ethyl for hypertriglyceridemia. N Engl J Med 2019;380: 11–22.

2. Gaba P, Bhatt DL, Steg PG, et al. Prevention of cardiovascular events and mortality with icosapent ethyl in patients with prior myocardial infarction. J Am Coll Cardiol 2022;79:1660–71.

Find this article online at Eur Heart J.

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