AHA 2018 — Icosapent ethyl reduced major adverse cardiovascular events

  • Hao Cheng, MD
  • Conference Reports
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  • Icosapent ethyl significantly reduced important cardiovascular events by 25% compared with placebo.

Why this matters

  • Icosapent ethyl was known to lower triglyceride levels, but it was unclear this translated to decreased ischemic events.

Study design

  • Multicenter, randomized, double-blind, placebo-controlled trial. 
  • Patients with cardiovascular disease or with diabetes and other risk factors, on statin therapy, with fasting triglyceride level of 135-499 mg per deciliter (1.52-5.63 mmol per liter) and a low-density lipoprotein (LDL) level of 41-100 mg per deciliter (1.06-2.59 mmol/L).
  • Patients were randomly assigned to receive 2 g of icosapent ethyl twice daily (total daily dose, 4 g) or placebo.
  • Primary endpoint was a composite of cardiovascular death, nonfatal myocardial infarction (MI), nonfatal stroke, coronary revascularization, or unstable angina.

Key results

  • 8179 patients were enrolled and followed for a median of 4.9 years.
  • Primary endpoint event occurred in 17.2% of patients in the icosapent ethyl group compared with 22.0% for placebo HR (CL 95%) = 0.75 (0.68-0.83) (P<.001>
  • Additional ischemic endpoints were significantly lower in the icosapent ethyl group, including the rate of cardiovascular death HR (CL 95%) = 0.80 (0.66-0.98) (P=.03).
  • From the standpoint of effect size, icosapent ethyl reduced the rate of important cardiovascular events by 25%, including a 20% reduction in death from cardiovascular causes, a 31% reduction in MI, and a 28% reduction in strokes.


  • Little use of ezetimibe or PCSK9 inhibitors.

Expert comment

  • "REDUCE-IT supports the position that Icosapent ethyl is safe, well-tolerated, and reduces the likelihood of cardiovascular events in stable, high-risk hypertriglyceridemia patients taking evidence-based statin therapy. Unlike other drugs shown to be effective as add-ons to statins, it appears to work via a mechanism that is unrelated to the upregulation of LDL receptor expression." — Carl Orringer, MD, University of Miami.