Cardiovascular Outcomes With Icosapent Ethyl by Baseline Low-Density Lipoprotein Cholesterol: A Secondary Analysis of the REDUCE-IT Randomized Trial.

Background: The efficacy of icosapent ethyl among patients with very well-controlled baseline low-density lipoprotein cholesterol (LDL-C) is unknown.
Methods: In this post hoc analysis of the REDUCE-IT (Reduction of Cardiovascular Events With Icosapent Ethyl-Intervention Trial) randomized clinical trial, statin-treated patients with high cardiovascular risk, elevated triglycerides (135-499 mg/dL), and baseline LDL-C of 41 to 100 mg/dL were included. Patients were randomized to icosapent ethyl (2 g twice daily) or placebo and then post hoc stratified by baseline LDL-C (<55 mg/dL versus ≥55 mg/dL). The primary composite end point included cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, coronary revascularization, or unstable angina.
Results: Among 8175 patients with baseline LDL-C data, 7117 (87.1%) had LDL-C ≥55 mg/dL and 1058 (12.9%) had LDL-C <55 mg/dL. In patients with LDL-C <55 mg/dL, the rate of the primary composite end point was lower in the icosapent ethyl group (16.2% versus 22.8%) than in the placebo group (hazard ratio [HR], 0.66 [95% CI, 0.50-0.87]; absolute risk reduction, 6.6%; P =0.003). Among patients with LDL-C ≥55 mg/dL, a primary composite end point event occurred in a lower proportion of patients in the icosapent ethyl group (17.4% versus 21.9%) than in the placebo group (HR, 0.76 [95% CI, 0.69-0.85]; absolute risk reduction, 4.5%; P <0.0001). No significant interaction was observed between baseline LDL-C and treatment group ( P for interaction=0.40). Findings were consistent among secondary cardiovascular end points and in sensitivity analyses.
Conclusions: Among statin-treated patients with elevated triglycerides and high cardiovascular risk, icosapent ethyl reduced the rate of cardiovascular end points irrespective of baseline LDL-C, including among eligible patients with optimal LDL-C control.
Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01492361.