Reduction in Revascularization With Icosapent Ethyl: Insights From REDUCE-IT Revascularization Analyses

Circulation. 2021 Jan 5;143(1):33-44. doi: 10.1161/CIRCULATIONAHA.120.050276. Epub 2020 Nov 5.


Background: Patients with elevated triglycerides despite statin therapy have increased risk for ischemic events, including coronary revascularizations.

Methods: REDUCE-IT (The Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial), a multicenter, double-blind, placebo-controlled trial, randomly assigned statin-treated patients with elevated triglycerides (135-499 mg/dL), controlled low-density lipoprotein (41-100 mg/dL), and either established cardiovascular disease or diabetes plus other risk factors to receive icosapent ethyl 4 g/d or placebo. The primary and key secondary composite end points were significantly reduced. Prespecified analyses examined all coronary revascularizations, recurrent revascularizations, and revascularization subtypes.

Results: A total of 8179 randomly assigned patients were followed for 4.9 years (median). First revascularizations were reduced to 9.2% (22.5/1000 patient-years) with icosapent ethyl versus 13.3% (33.7/1000 patient-years) with placebo (hazard ratio, 0.66 [95% CI, 0.58-0.76]; P<0.0001; number needed to treat for 4.9 years=24); similar reductions were observed in total (first and subsequent) revascularizations (negative binomial rate ratio, 0.64 [95% CI, 0.56-0.74]; P<0.0001), and across elective, urgent, and emergent revascularizations. Icosapent ethyl significantly reduced percutaneous coronary intervention (hazard ratio, 0.68 [95% CI, 0.59-0.79]; P<0.0001) and coronary artery bypass grafting (hazard ratio, 0.61 [95% CI, 0.45-0.81]; P=0.0005).

Conclusions: Icosapent ethyl reduced the need for first and subsequent coronary revascularizations in statin-treated patients with elevated triglycerides and increased cardiovascular risk. To our knowledge, icosapent ethyl is the first non-low-density lipoprotein-lowering treatment that has been shown to reduce coronary artery bypass grafting in a blinded, randomized trial. Registration: URL:; Unique identifier: NCT01492361.

Keywords: eicosapentaenoic acid; icosapent ethyl; myocardial revascularization; prevention & control.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Cardiovascular Diseases / drug therapy*
  • Cardiovascular Diseases / physiopathology
  • Diabetes Mellitus / drug therapy*
  • Diabetes Mellitus / physiopathology
  • Double-Blind Method
  • Eicosapentaenoic Acid / analogs & derivatives*
  • Eicosapentaenoic Acid / therapeutic use
  • Female
  • Follow-Up Studies
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use
  • Male
  • Middle Aged
  • Myocardial Revascularization / methods*
  • Platelet Aggregation Inhibitors / therapeutic use*


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

Associated data