Highly purified omega-3 fatty acid lowers first and recurrent ischemic events in hypertriglyceridemia

Introduction and methods

News - Mar. 19, 2019

The Reduction of Cardiovascular Events with Icosapent Ethyl–Intervention Trial (REDUCE-IT) had previously shown a 25% reduction of the first occurrence of a major adverse CV event (MACE) with treatment with 4 grams of icosapent ethyl, a pure and stable prescription form of the omega-3 fatty acid EPA as compared with placebo, in patients with hypertriglyceridemia at high risk.

19.212 patients with established CVD (secondary prevention cohort) or ≥50 years with diabetes with ≥1 additional risk factor for CVD (primary prevention cohort) with fasting TG levels ≥135 mg/dL and <500 mg/dL and LDL-c between 40 and 100 mg/dL and on stable statin therapy +/- ezetimibe were included in the REDUCE-IT. The primary endpoint was a composite of CV death, nonfatal MI, nonfatal stroke, coronary revascularization and hospitalization for unstable angina. The primary analysis only considered first events. This analysis of REDUCE-IT looked at the totality of events, thus potential subsequent events in the same patients.

Main results

  • As published previously, the first occurrence of primary endpoint events was lowered by 25% with icosapent ethyl vs. placebo (23.0% vs. 28.3%, HR: 0.75, 95%CI: 0.68-0.83, RRR: 24.9%, ARR: 4.8% and NNT: 21).
  • Of total adjudicated events seen in the study, 55% (n=1606) were first events, and the remaining 45% (n=1303) were subsequent events.
  • When looking at subsequent events, icosapent ethyl when compared with placebo lowered the risk of 2nd events by 32% (HR: 0.68, 95%CI: 0.60-0.78), of 3rd events by 31% (HR: 0.69, 95%CI: 0.59-0.82) and by ≥4th events by 48% (RR: 0.52, 95%CI: 0.38-0.70).
  • Overall, when considering total events, icosapent ethyl reduced events by 30% (RR: 0.70, 95%CI: 0.2-0.78, P=0.00000000036).
  • When looking at tertiles of baseline TG level, it was noted that the total event rate in the placebo group increased in the higher tertiles (74.5, 86.8 and 107.4 per 1000 patient-years, respectively). In the lowest tertile (≥81 – 190 mg/dL), RR was 0.74 (95%CI: 0.61-0.90) with icosapent ethyl vs placebo, in the middle tertile (190 – 250 mg/dL) RR was 0.77 (95%CI: 0.63-0.95) and in the highest tertile RR was 0.60 (95%CI: 0.50-0.73).


This analysis shows that, when compared with placebo, icosapent ethyl 4g/day significantly lowered total CV events by 30%, including 25% fewer first events, 32% fewer second, 31% fewer third and 48% fewer fourth or more events. This indicates the large burden of ischemic events in statin-treated patients with baseline TG levels > ~100 mg/dL and the potential of icosapent ethyl in reducing this residual risk.

Bhatt added that for every 1000 patients treated with icosapent ethyl for 5 years, 12 CV deaths could be prevented, 42 fatal or nonfatal MI, 14 fatal or nonfatal stroke, 76 coronary revascularizations and 16 hospitalization for unstable angina could be avoided (total 159 primary composite endpoint events).


The discussant Eileen Handberg noted that in clinical trials, it is not common to look at subsequent events, but they matter a great deal for patients. This study demonstrated that patients with CVD often have multiple events. And that they can be reduced. She thinks that this type of analysis should be done more often, to get a better idea of the total burden of disease and what can be done about it.

- Our coverage of ACC.19 is based on the information provided during the congress -

Watch our video of the REDUCE-IT trial

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