Alirocumab reduces total nonfatal cardiovascular and fatal events: The ODYSSEY OUTCOMES trial

  • Background: The ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) trial compared alirocumab with placebo, added to high-intensity or maximum-tolerated statin treatment, after acute coronary syndrome (ACS) in 18,924 patients. Alirocumab reduced the first occurrence of the primary composite endpoint and was associated with fewer all-cause deaths. Objectives: This pre-specified analysis determined the extent to which alirocumab reduced total (first and subsequent) nonfatal cardiovascular events and all-cause deaths in ODYSSEY OUTCOMES. Methods: Hazard functions for total nonfatal cardiovascular events (myocardial infarction, stroke, ischemia-driven coronary revascularization, and hospitalization for unstable angina or heart failure) and death were jointly estimated, linked by a shared frailty accounting for patient risk heterogeneity and correlated within-patient nonfatal events. An association parameter also quantified the strength of the linkage between risk of nonfatal events and death. The model provides accurate relative estimates of nonfatal event risk if nonfatal events are associated with increased risk for death. Results: With 3,064 first and 5,425 total events, 190 fewer first and 385 fewer total nonfatal cardiovascular events or deaths were observed with alirocumab compared with placebo. Alirocumab reduced total nonfatal cardiovascular events (hazard ratio: 0.87; 95% confidence interval: 0.82 to 0.93) and death (hazard ratio: 0.83; 95% confidence interval: 0.71 to 0.97) in the presence of a strong association between nonfatal and fatal event risk. Conclusions: In patients with ACS, the total number of nonfatal cardiovascular events and deaths prevented with alirocumab was twice the number of first events prevented. Consequently, total event reduction is a more comprehensive metric to capture the totality of alirocumab clinical efficacy after ACS.
Author:Michael Szarek, Harvey White, Gregory G. Schwartz, Marco Alings, Deepak L. BhattORCiDGND, Vera BittnerORCiD, Chern-En Chiang, Rafael Diaz, Jay M. Edelberg, Shaun G. Goodman, Corinne Hanotin, Robert A. Harrington, J. Wouter Jukema, Takeshi Kimura, Robert Gabor Kiss, Guillaume Lecorps, Kenneth Mahaffey, Angèle Moryusef, Robert Pordy, Matthew T. Roe, Pierluigi Tricoci, Denis Xavier, Andreas M. ZeiherORCiDGND, P. Gabriel Steg
Pubmed Id:
Parent Title (English):Journal of the American College of Cardiology
Publisher:Elsevier ; American College of Cardiology
Place of publication:New York, NY
Contributor(s):Sophie Rushton-Smith
Document Type:Article
Year of Completion:2018
Date of first Publication:2018/11/11
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2020/05/11
Tag:acute coronary syndrome; alirocumab; total events
Page Number:10
First Page:387
Last Page:396
This is an open access article under the CC BY-NC-ND license (
Institutes:Medizin / Medizin
Exzellenzcluster / Exzellenzcluster Herz-Lungen-System
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - Namensnennung-Nicht kommerziell - Keine Bearbeitung 4.0