Reducing residual cardiovascular risk

Reducing residual cardiovascular risk

Reducing residual cardiovascular risk in patients treated with statins and having hypertriglyceridemia was addressed by Reduction of Cardiovascular Events with Icosapent Ethyl–Intervention Trial (REDUCE-IT) [1].

REDUCE-IT was a double blind placebo controlled multicenter randomized trial. Patients with established cardiovascular disease or diabetes mellitus with other risk factors treated with statins were evaluated. At study inclusion they needed to have fasting triglyceride levels between 135 and 499 mg/dL and LDL cholesterol level 41 to 100 mg/dL.

They were randomized to either 2 g of icosapent ethyl twice daily or placebo. Icosapent ethyl is a highly purified eicosapentaenoic acid ethyl ester which lowers serum triglyceride levels.

Primary endpoint: Composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, coronary revascularization or unstable angina.

Secondary end point: Composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke.

Eight thousand one hundred and seventy nine patients were enrolled in REDUCE-IT, of which 70.7% were for secondary prevention of cardiovascular events. Median follow up period was 4.9 years.

Primary end-point event occurred in 17.2% of the patients in the study group, while it occurred in 22.0% of the placebo group (P<0.001).

Interestingly 3.1% of the active treatment group was hospitalized with atrial fibrillation or flutter while the same for placebo group was 2.1% (P=0.004). 

Serious bleeding events were also higher in the icosapent ethyl group (2.7% vs 2.1%) though it did not reach the level of statistical significance (P=0.06).

Finally, authors concluded that in patients with hypertriglyceridemia despite statin, the risk of ischemic events including cardiovascular death was significantly lower in those treated with 2g icosapent ethyl twice daily. 


  1. Bhatt DL, Steg PG, Miller M, Brinton EA, Jacobson TA, Ketchum SB, Doyle RT Jr, Juliano RA, Jiao L, Granowitz C, Tardif JC, Ballantyne CM; REDUCE-IT Investigators. Cardiovascular Risk Reduction with Icosapent Ethyl for Hypertriglyceridemia. N Engl J Med. 2019 Jan 3;380(1):11-22.