Background: REDUCE-IT (Reduction of Cardiovascular Events With Icosapent Ethyl-Intervention Trial) randomized statin-treated patients with elevated triglycerides to icosapent ethyl (IPE) or placebo. There was a significant reduction in adjudicated events, including the primary endpoint (cardiovascular [CV] death, myocardial infarction [MI], stroke, coronary revascularization, unstable angina requiring hospitalization) and key secondary endpoint (CV death, MI, stroke) with IPE.
Objectives: The purpose of this study was to determine the effects of IPE on investigator-reported events.
Methods: Potential endpoints were collected by blinded site investigators and subsequently adjudicated by a blinded Clinical Endpoint Committee (CEC) according to a prespecified charter. Investigator-reported events were compared with adjudicated events for concordance.
Results: There was a high degree of concordance between investigator-reported and adjudicated endpoints. The simple Kappa statistic between CEC-adjudicated vs site-reported events for the primary endpoint was 0.89 and for the key secondary endpoint was 0.90. Based on investigator-reported events in 8,179 randomized patients, IPE significantly reduced the rate of the primary endpoint (19.1% vs 24.6%; HR: 0.74 [95% CI: 0.67-0.81]; P < 0.0001) and the key secondary endpoint (10.5% vs 13.6%; HR: 0.75 [95% CI: 0.66-0.85]; P < 0.0001). Among adjudicated events, IPE similarly reduced the rate of the primary and key secondary endpoints.
Conclusions: IPE led to consistent, significant reductions in CV events, including MI and coronary revascularization, as determined by independent, blinded CEC adjudication as well as by blinded investigator-reported assessment. These results highlight the robust evidence for the substantial CV benefits of IPE seen in REDUCE-IT and further raise the question of whether adjudication of CV outcome trial endpoints is routinely required in blinded, placebo-controlled trials. (Evaluation of the Effect of AMR101 on Cardiovascular Health and Mortality in Hypertriglyceridemic Patients With Cardiovascular Disease or at High Risk for Cardiovascular Disease: REDUCE-IT [Reduction of Cardiovascular Events With EPA - Intervention Trial]; NCT01492361).
Keywords: central adjudication; clinical trials; icosapent ethyl; investigator-reported endpoints.
Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.