Abstract | BACKGROUND: 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).
|
Authors | Prakriti Gaba, Deepak L Bhatt, Robert P Giugliano, Ph Gabriel Steg, Michael Miller, Eliot A Brinton, Terry A Jacobson, Steven B Ketchum, Rebecca A Juliano, Lixia Jiao, Ralph T Doyle Jr, Craig Granowitz, Jean-Claude Tardif, Christie M Ballantyne, Duane S Pinto, Matthew J Budoff, C Michael Gibson |
Journal | Journal of the American College of Cardiology
(J Am Coll Cardiol)
Vol. 78
Issue 15
Pg. 1525-1537
(10 12 2021)
ISSN: 1558-3597 [Electronic] United States |
PMID | 34620410
(Publication Type: Clinical Trial, Phase III, Journal Article, Randomized Controlled Trial)
|
Copyright | Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved. |
Chemical References |
- Lipid Regulating Agents
- eicosapentaenoic acid ethyl ester
- Eicosapentaenoic Acid
|
Topics |
- Aged
- Angina, Unstable
(epidemiology)
- Eicosapentaenoic Acid
(analogs & derivatives, therapeutic use)
- Endpoint Determination
- Female
- Humans
- Hypertriglyceridemia
(drug therapy)
- Lipid Regulating Agents
(therapeutic use)
- Male
- Myocardial Infarction
(epidemiology)
- Myocardial Revascularization
(statistics & numerical data)
- Stroke
(epidemiology)
|