Author + information
- Received April 4, 2019
- Revision received June 17, 2019
- Accepted July 2, 2019
- Published online August 26, 2019.
- Shaun G. Goodman, MD, MSca,∗ (, )@gabrielsteg,
- Philip E. Aylward, MDb,
- Michael Szarek, PhDc,
- Vakhtang Chumburidze, MDd,
- Deepak L. Bhatt, MD, MPHe,
- Vera A. Bittner, MD, MSPHf,
- Rafael Diaz, MDg,
- Jay M. Edelberg, MD, PhDh,
- Corinne Hanotin, MDi,
- Robert A. Harrington, MDj,
- J. Wouter Jukema, MD, PhDk,
- Sasko Kedev, MDl,
- Alexia Letierce, PhDi,
- Angele Moryusef, MDh,
- Robert Pordy, MDm,
- Gabriel Arturo Ramos López, MDn,
- Matthew T. Roe, MD, MHSo,p,
- Margus Viigimaa, MDq,
- Harvey D. White, DScr,
- Andreas M. Zeiher, MDs,
- Ph. Gabriel Steg, MDt,u,
- Gregory G. Schwartz, MD, PhDv,
- for the ODYSSEY OUTCOMES Committees and Investigators∗
- aCanadian VIGOUR Centre, University of Alberta, Edmonton, Alberta, Canada and St. Michael’s Hospital, University of Toronto, Toronto, Ontario, Canada
- bSouth Australian Health and Medical Research Institute, Flinders University and Medical Centre, Adelaide, South Australia, Australia
- cState University of New York, Downstate School of Public Health, Brooklyn, New York
- dChapidze Emergency Cardiology Center, Tbilisi, Georgia
- eBrigham and Women's Hospital Heart & Vascular Center and Harvard Medical School, Boston, Massachusetts
- fDivision of Cardiovascular Disease, University of Alabama at Birmingham, Birmingham, Alabama
- gEstudios Cardiológicos Latinoamérica, Instituto Cardiovascular de Rosario, Rosario, Argentina
- hSanofi, Bridgewater, New Jersey
- iSanofi, Chilly-Mazarin, France
- jStanford Center for Clinical Research, Department of Medicine, Stanford University, Stanford, California
- kDepartment of Cardiology, Leiden University Medical Center, Leiden, the Netherlands
- lUniversity Clinic of Cardiology, Skopje, Macedonia
- mRegeneron Pharmaceuticals Inc., Tarrytown, New York
- nMedical Office, Guadalajara, Jalisco, Mexico
- oDuke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina
- pDivision of Cardiology, Department of Medicine, Duke University School of Medicine, Durham, North Carolina
- qSA Põhja-Eesti Regionaalhaigla, Tallinn, Estonia
- rGreen Lane Cardiovascular Services Auckland City Hospital, Auckland, New Zealand
- sDepartment of Medicine III, Goethe University, Frankfurt am Main, Germany
- tAssistance Publique-Hôpitaux de Paris, Hôpital Bichat, Paris, France
- uNational Heart and Lung Institute, Imperial College, Royal Brompton Hospital, London, United Kingdom
- vDivision of Cardiology, University of Colorado School of Medicine, Aurora, Colorado
- ↵∗Address for correspondence:
Dr. Shaun G. Goodman, St. Michael’s Hospital, Room 6-034 Donnelly Wing, Toronto, Ontario M5B 1W8, Canada.
Background Patients with acute coronary syndrome (ACS) and history of coronary artery bypass grafting (CABG) are at high risk for recurrent cardiovascular events and death.
Objectives This study sought to determine the clinical benefit of adding alirocumab to statins in ACS patients with prior CABG in a pre-specified analysis of ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab).
Methods Patients (n = 18,924) 1 to 12 months post-ACS with elevated atherogenic lipoprotein levels despite high-intensity statin therapy were randomized to alirocumab or placebo subcutaneously every 2 weeks. Median follow-up was 2.8 years. The primary composite endpoint of major adverse cardiovascular events (MACE) comprised coronary heart disease death, nonfatal myocardial infarction, ischemic stroke, or unstable angina requiring hospitalization. All-cause death was a secondary endpoint. Patients were categorized by CABG status: no CABG (n = 16,896); index CABG after qualifying ACS, but before randomization (n = 1,025); or CABG before the qualifying ACS (n = 1,003).
Results In each CABG category, hazard ratios (95% confidence intervals) for MACE (no CABG 0.86 [0.78 to 0.95], index CABG 0.85 [0.54 to 1.35], prior CABG 0.77 [0.61 to 0.98]) and death (0.88 [0.75 to 1.03], 0.85 [0.46 to 1.59], 0.67 [0.44 to 1.01], respectively) were consistent with the overall trial results (0.85 [0.78 to 0.93] and 0.85 [0.73 to 0.98], respectively). Absolute risk reductions (95% confidence intervals) differed across CABG categories for MACE (no CABG 1.3% [0.5% to 2.2%], index CABG 0.9% [−2.3% to 4.0%], prior CABG 6.4% [0.9% to 12.0%]) and for death (0.4% [−0.1% to 1.0%], 0.5% [−1.9% to 2.9%], and 3.6% [0.0% to 7.2%]).
Conclusions Among patients with recent ACS and elevated atherogenic lipoproteins despite intensive statin therapy, alirocumab was associated with large absolute reductions in MACE and death in those with CABG preceding the ACS event. (ODYSSEY OUTCOMES: Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab; NCT01663402)
The trial was funded by Sanofi and Regeneron Pharmaceuticals, Inc. Dr. Goodman has received research grants from Daiichi-Sankyo, Luitpold Pharmaceuticals, Merck, Novartis, Servier, Regeneron Pharmaceuticals Inc., Sanofi, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, CSL Behring, Eli Lilly, Pfizer, and Tenax Therapeutics; has received honoraria from Bristol-Myers Squibb, Eli Lilly, Fenix Group International, Ferring Pharmaceuticals, Merck, Novartis, Pfizer, Servier, Regeneron Pharmaceuticals Inc., Sanofi, Amgen, AstraZeneca, Bayer, and Boehringer Ingelheim; and has served as a consultant/on the Advisory Board for AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, Pfizer, Servier, Tenax Therapeutics, Sanofi, Amgen, and Bayer. Dr. Aylward has received grants and personal fees from Sanofi, AstraZeneca, and Bayer; has received personal fees from Amgen, Boehringer Ingelheim, and Novartis; and has received grants from CSL. Dr. Szarek has served as a consultant to/on the Advisory Board for CiVi, Resverlogix, Baxter, and Regeneron Pharmaceuticals. Dr. Bhatt has served on an Advisory Board for Cardax, Elsevier Practice Update Cardiology, Medscape Cardiology, and Regado Biosciences; Board of Directors for Boston VA Research Institute, Society of Cardiovascular Patient Care, and TobeSoft; Chair of American Heart Association Quality Oversight Committee; Data Monitoring Committees for Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute, for the PORTICO trial, funded by St. Jude Medical, now Abbott), Cleveland Clinic (including for the ExCEED trial, funded by Edwards), Duke Clinical Research Institute, Mayo Clinic, Mount Sinai School of Medicine (for the ENVISAGE trial, funded by Daiichi-Sankyo), and Population Health Research Institute; honoraria from American College of Cardiology (Senior Associate Editor, Clinical Trials and News, ACC.org; Vice-Chair, ACC Accreditation Committee), Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute; RE-DUAL PCI clinical trial steering committee funded by Boehringer Ingelheim), Belvoir Publications (Editor-in-Chief, Harvard Heart Letter), Duke Clinical Research Institute (clinical trial steering committees), HMP Global (Editor-in-Chief, Journal of Invasive Cardiology), Journal of the American College of Cardiology (Guest Editor; Associate Editor), Population Health Research Institute (for the COMPASS operations committee, publications committee, steering committee, and USA national co-leader, funded by Bayer), Slack Publications (Chief Medical Editor, Cardiology Today’s Intervention), Society of Cardiovascular Patient Care (Secretary/Treasurer), and WebMD (CME steering committees); other for Clinical Cardiology (Deputy Editor), NCDR-ACTION Registry Steering Committee (Chair), VA CART Research and Publications Committee (Chair); research funding from Abbott, Amarin, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Chiesi, Eisai, Ethicon, Forest Laboratories, Idorsia, Ironwood, Ischemix, Lilly, Medtronic, PhaseBio, Pfizer, Regeneron, Roche, Sanofi, Synaptic, and The Medicines Company; royalties from Elsevier (Editor, Cardiovascular Intervention: A Companion to Braunwald’s Heart Disease); site co-investigator for Biotronik, Boston Scientific, St. Jude Medical (now Abbott), and Svelte; trustee for American College of Cardiology; and unfunded research for FlowCo, Fractyl, Merck, Novo Nordisk, PLx Pharma, and Takeda. Dr. Bittner has received research grants from Amgen, DalCor, Esperion, Sanofi, AstraZeneca, and Bayer Healthcare; has received honoraria from American College of Cardiology, American Heart Association, and National Lipid Association; and has served as consultant to/on the Advisory Board for Sanofi. Dr. Diaz has received research grants from Sanofi, Amgen, Bayer, Dalcor, PHRI, and DCRI; and has received honoraria from Sanofi. Dr. Edelberg is an employee of Sanofi. Dr. Hanotin is an employee of Sanofi. Dr. Harrington has received research grants from Apple, CSL, Sanofi, Astra, Portola, Janssen, BMS, Novartis, and The Medicines Company; has served as a consultant to/on the Advisory Board for Amgen, Bayer, Gilead, MyoKardia, and WebMD; and has served on the board of directors (unpaid) for AHA and Stanford HealthCare. Dr. Jukema has received research grants from the Netherlands Heart Foundation, the Interuniversity Cardiology Institute of the Netherlands, and the European Community Framework KP7 Program; and has received other research support from Amgen, Astellas, AstraZeneca, Daiichi-Sankyo, Lilly, Merck-Schering-Plough, Pfizer, Roche, and Sanofi. Dr. Letierce is an employee of Sanofi. Dr. Moryusef is an employee of Sanofi. Dr. Pordy is an employee of Regeneron Pharmaceuticals. Dr. Ramos López has received personal fees and nonfinancial support from Sanofi. Dr. Roe has received research grant funding from Sanofi, Janssen, AstraZeneca, Patient-Centered Outcomes Research Institute, Ferring Pharmaceuticals, MyoKardia, American College of Cardiology, American Heart Association, and Familial Hypercholesterolemia Foundation; and has received consulting fees or honoraria from AstraZeneca, Amgen, Eli Lilly, Roche-Genentech, Janssen, Regeneron Pharmaceuticals, Ardea Biosciences, Novo Nordisk, Flatiron, Merck, Pfizer, Sanofi, Signal Path, and Elsevier. Dr. Viigimaa has received research grants and personal fees from Amgen; and has received personal fees from Sanofi, Menarini, and NovoNordisk. Dr. White has received grant support (paid to institution) and fees for serving on a Steering Committee from Sanofi and Regeneron Pharmaceuticals (for the ODYSSEY OUTCOMES trial), Eli Lilly (for the ACCELERATE trial), Omthera Pharmaceuticals (for the STRENGTH trial), Pfizer (for the SPIRE trial), American Regent (for the HEART-FID trial), Eisai (for the CAMELLIA-TIMI trial), DalCor (for the dal-GenE trial), CSL Behring (for the AEGIS-II trial), Sanofi (for the SCORED and SOLOIST trials), and Esperion Therapeutics (for the CLEAR Outcomes trial). Dr. Steg has received research grants from Bayer, Merck, Sanofi, and Servier; and has received speaking or consulting fees from Amarin, Amgen, AstraZeneca, Bayer/Janssen, Boehringer Ingelheim, Bristol-Myers Squibb, Lilly, Merck, Novartis, Novo-Nordisk, Pfizer, Regeneron Pharmaceuticals, Inc., Sanofi, and Servier. Dr. Schwartz is co-inventor of pending U.S. patent 14/657192 assigned in full to the University of Colorado; and has received research grants to his institution from Resverlogix, Sanofi, Roche, and The Medicines Company.
Listen to this manuscript's audio summary by Editor-in-Chief Dr. Valentin Fuster on JACC.org.
- Received April 4, 2019.
- Revision received June 17, 2019.
- Accepted July 2, 2019.
- 2019 American College of Cardiology Foundation
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