Generalizability of the REDUCE-IT trial and cardiovascular outcomes associated with hypertriglyceridemia among patients potentially eligible for icosapent ethyl therapy: An analysis of the REduction of Atherothrombosis for Continued Health (REACH) registry.

BACKGROUND

The REDUCE-IT (Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial) trial demonstrated that high-dose icosapent-ethyl reduced the risk of ischemic events in statin-treated patients with elevated triglycerides (TG) and either atherosclerotic cardiovascular disease (ASCVD) or diabetes plus at least one risk factor.

METHODS AND RESULTS

Using data from REACH (Reduction of Atherothrombosis for Continued Health), a large international registry of outpatients with or at risk of ASCVD, we evaluated the proportion of patients potentially eligible for enrolment in REDUCE-IT and compared their outcomes to those excluded because of low TG. Among 62,464 patients with either ASCVD or diabetes enrolled in the REACH Registry, 1036/8418 (12.3%) patients in primary prevention and 6049/54046 (11.2%) patients in secondary prevention (11.3% overall) would have been eligible for inclusion in REDUCE-IT. Compared with patients excluded for low TG level, adjusted risk of the primary composite outcome of cardiovascular death, non-fatal myocardial infarction (MI), non-fatal stroke, unstable angina, or coronary revascularization was higher in the REDUCE-IT eligible group (HR:1.06, 95%CI:1.00-1.13, p = 0.04). In addition, unstable angina, non-fatal MI, percutaneous coronary intervention and coronary artery bypass grafting were also more frequent in the REDUCE-IT eligible group (HR:1.17, 95%CI:1.07-1.27, p < 0.001; HR:1.25, 95%CI:1.07-1.45, p < 0.001; HR:1.42, 95%CI:1.27-1.57, p < 0.001; HR:1.43, 95%CI:1.19-1.71, p < 0.001, respectively), whereas the adjusted risk of non-fatal stroke was lower (HR:0.64, 95%CI:0.54-0.75, p < 0.001).

CONCLUSION

In this large international registry of patients with or at high-risk of ASCVD, 11.3% met the REDUCE-IT trial selection criteria. REDUCE-IT eligible patients were found to be at higher risk of cardiac atherothrombotic events, but at lower risk of stroke than trial-ineligible patients with lower TG.