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J Am Coll Cardiol. 2019 Feb 5;73(4):387-396. doi: 10.1016/j.jacc.2018.10.039. Epub 2018 Nov 11.

Alirocumab Reduces Total Nonfatal Cardiovascular and Fatal Events: The ODYSSEY OUTCOMES Trial.

Author information

1
State University of New York, Downstate School of Public Health, Brooklyn, New York. Electronic address: michael.szarek@downstate.edu.
2
University of Auckland and Green Lane Cardiovascular Services Auckland City Hospital, Auckland, New Zealand.
3
Division of Cardiology, University of Colorado School of Medicine, Aurora, Colorado.
4
Amphia Ziekenhuis Molengracht, Breda, the Netherlands.
5
Brigham and Women's Hospital Heart & Vascular Center and Harvard Medical School, Boston, Massachusetts. Electronic address: https://twitter.com/DLBHATTMD.
6
Division of Cardiovascular Disease, University of Alabama at Birmingham, Birmingham, Alabama.
7
General Clinical Research Center, Taipei Veterans General Hospital and National Yang-Ming University, Taipei, Taiwan.
8
Estudios Cardiológicos Latinoamérica, Instituto Cardiovascular de Rosario, Rosario, Argentina.
9
Sanofi, Bridgewater, New Jersey.
10
Canadian VIGOUR Centre, University of Alberta, Edmonton, Alberta, and St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada.
11
Sanofi, Paris, France.
12
Stanford Center for Clinical Research, Department of Medicine, Stanford University, Stanford, California.
13
Department of Cardiology, Leiden University Medical Center, Leiden, the Netherlands.
14
Kyoto University Graduate School of Medicine, Kyoto-shi, Kyoto, Japan.
15
Magyar Honvédség Egészségügyi Központ, Budapest, Hungary.
16
Regeneron Pharmaceuticals Inc., Tarrytown, New York.
17
Division of Cardiology, Department of Medicine, Duke University School of Medicine, Durham, North Carolina; Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina.
18
Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina.
19
Department of Pharmacology and Division of Clinical Research, St. John's Medical College and Research Institute, Bangalore, India.
20
Department of Medicine III, Goethe University, Frankfurt am Main, Germany.
21
Assistance Publique-Hôpitaux de Paris, Hôpital Bichat, Paris and Paris Diderot University, Sorbonne Paris Cité, FACT (French Alliance for Cardiovascular Trials), INSERM U1148, Paris, France; National Heart and Lung Institute, Imperial College, Royal Brompton Hospital, London, United Kingdom. Electronic address: https://twitter.com/gabrielsteg.

Abstract

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.

KEYWORDS:

acute coronary syndrome; alirocumab; total events

PMID:
30428396
DOI:
10.1016/j.jacc.2018.10.039
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