Impact of Icosapent Ethyl on Cardiovascular Risk Reduction in Patients With Heart Failure in REDUCE-IT

J Am Heart Assoc. 2022 Apr 5;11(7):e024999. doi: 10.1161/JAHA.121.024999. Epub 2022 Apr 4.


Background Patients with heart failure (HF) are at high risk for atherosclerotic cardiovascular disease. Studies of atherothrombotic treatments in this population have been disappointing to date. Icosapent ethyl reduced the risk of atherosclerotic cardiovascular disease among a broad array of statin-treated patients at elevated risk for atherosclerotic cardiovascular disease. Whether the treatment benefits of icosapent ethyl are consistent among those with HF is unknown. Methods and Results REDUCE-IT (Reduction of Cardiovascular Events With Icosapent Ethyl-Intervention Trial) randomized 8179 participants, including 1446 (17.7%) patients with a history of HF (icosapent ethyl, N=703; and placebo, N=743). The primary end point was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, coronary revascularization, or unstable angina. We used Cox regression to estimate the risk of outcomes of participants with and without HF. We estimated the placebo-controlled change in triglycerides and hs-CRP (high-sensitivity C-reactive protein) from baseline to 2 years. Among 1446 patients with HF, median age was 63.0 years, median body mass index was 31.0 kg/m2, and more were men (69.3%). Icosapent ethyl reduced triglycerides (median reduction, 33.5 mg/dL, or 15.4%; P<0.0001) and hs-CRP (35.1%; P<0.0001) compared with placebo, similar to patients without HF (P-interaction>0.90). The treatment effect on the primary end point in patients with HF history (hazard ratio [HR], 0.87; 95% CI, 0.70-1.08) was consistent with the effects observed in patients without HF history (HR, 0.73; 95% CI, 0.65-0.81) (P-interaction=0.13). Conclusions In REDUCE-IT, icosapent ethyl provided similar improvements in triglyceride levels and hs-CRP as well as similar cardiovascular risk reduction in patients with and without HF. Registration URL:; Unique identifier: NCT01492361.

Keywords: eicosapentaenoic acid; heart failure; prevention.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cardiovascular Diseases* / chemically induced
  • Cardiovascular Diseases* / epidemiology
  • Cardiovascular Diseases* / prevention & control
  • Eicosapentaenoic Acid / adverse effects
  • Eicosapentaenoic Acid / analogs & derivatives
  • Heart Disease Risk Factors
  • Heart Failure* / chemically induced
  • Heart Failure* / drug therapy
  • Heart Failure* / epidemiology
  • Humans
  • Male
  • Middle Aged
  • Risk Factors


  • eicosapentaenoic acid ethyl ester
  • Eicosapentaenoic Acid

Associated data