(P238) ICOSAPENT ETHYL REDUCES MACE IN PATIENTS WITH ELEVATED TRIGLYCERIDES AND HIGH OR LOW LIPOPROTEIN(A) CONCENTRATIONS: A REDUCE-IT SUBANALYSIS

Background: Lipoprotein(a) (Lp(a)) concentration is related to cardiovascular (CV) event risk among individuals with elevated LDL-C. Whether this relationship holds among those with elevated triglycerides (TG) and well-controlled LDL-C is unknown.

METHODS AND RESULTS: In REDUCE-IT, 8179 patients receiving statin therapy with established CV disease or diabetes and ≥1 additional risk factor, fasting TG 150 – 499 mg/dL, and LDL-C 41 – 100 mg/dL were randomized to receive 2g twice daily of icosapent ethyl (IPE) or matching placebo and followed for a median 4.9 years. The relationship between continuous baseline Lp(a) mass concentration and risk of MACE (death from CV disease, non-fatal myocardial infarction or stroke, coronary revascularization, or unstable angina) was analyzed by proportional hazards models with a natural cubic spline of Lp(a) as the predictor variable and adjustment for baseline LDL-C, baseline TG, and treatment assignment. Lp(a) had a significant relationship with MACE across treatment groups (spline P< 0.0001; Figure Panel A) while the treatment benefit of IPE was consistent across concentrations (interaction P=0.66; Panel B). By KM analyses, MACE absolute risk reduction at 5 years with IPE was 6.5% and 5.7% for those with Lp(a) ≥50 mg/dL and < 50 mg/dL, respectively.

Conclusion: Among patients with elevated TG levels receiving statin therapy, baseline Lp(a) concentration was prognostic for MACE. Importantly, IPE reduced MACE among those with either high or low Lp(a) levels.