Comparative Reductions in Investigator-Reported and Adjudicated Ischemic Events in REDUCE-IT
Bhatt, Deepak L
Giugliano, Robert P
Steg, Ph Gabriel
Brinton, Eliot A
Jacobson, Terry A
Ketchum, Steven B
Juliano, Rebecca A
Doyle, Ralph T
Ballantyne, Christie M
Pinto, Duane S
Budoff, Matthew J
Gibson, C Michael
JournalJournal of the American College of Cardiology
MetadataShow full item record
AbstractBackground: 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).
Rights/TermsCopyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.
Identifier to cite or link to this itemhttp://hdl.handle.net/10713/16850
- Prevention of Cardiovascular Events and Mortality With Icosapent Ethyl in Patients With Prior Myocardial Infarction.
- Authors: Gaba P, Bhatt DL, Steg PG, Miller M, Brinton EA, Jacobson TA, Ketchum SB, Juliano RA, Jiao L, Doyle RT Jr, Granowitz C, Tardif JC, Giugliano RP, Martens FMAC, Gibson CM, Ballantyne CM, REDUCE-IT Investigators.
- Issue date: 2022 May 3
- Characterization of cardiovascular clinical events and impact of event adjudication on the treatment effect of darapladib versus placebo in patients with stable coronary heart disease: Insights from the STABILITY trial.
- Authors: Held C, White HD, Stewart RAH, Davies R, Sampson S, Chiswell K, Silverstein A, Lopes RD, Heldestad U, Budaj A, Mahaffey KW, Wallentin L, STABILITY Investigators.
- Issue date: 2019 Feb
- Effects of Icosapent Ethyl on Total Ischemic Events: From REDUCE-IT.
- Authors: Bhatt DL, Steg PG, Miller M, Brinton EA, Jacobson TA, Ketchum SB, Doyle RT Jr, Juliano RA, Jiao L, Granowitz C, Tardif JC, Gregson J, Pocock SJ, Ballantyne CM, REDUCE-IT Investigators.
- Issue date: 2019 Jun 11
- REDUCE-IT Eligibility and Preventable Cardiovascular Events in the US Population (from the National Health and Nutrition Examination Survey [NHANES]).
- Authors: Wong ND, Fan W, Philip S, Granowitz C, Toth PP
- Issue date: 2020 Nov 1
- Reducing residual cardiovascular risk in Europe: Therapeutic implications of European medicines agency approval of icosapent ethyl/eicosapentaenoic acid.
- Authors: Chapman MJ, Zamorano JL, Parhofer KG
- Issue date: 2022 Mar 15