Author + information
- Received April 9, 2019
- Accepted April 16, 2019
- Published online June 24, 2019.
- Arthur Darmon, MDa,
- Emmanuel Sorbets, MD, PhDa,b,
- Gregory Ducrocq, MD, PhDa,c,
- Yedid Elbez, MSca,
- Jeremie Abtan, MDa,
- Batric Popovic, MDd,
- E. Magnus Ohman, MDe,
- Joachim Röther, MD, PhDf,
- Peter F. Wilson, MDg,
- Gilles Montalescot, MD, PhDh,
- Uwe Zeymer, MDi,
- Deepak L. Bhatt, MD, MPHj,
- Philippe Gabriel Steg, MDa,b,k,∗ (, )
- on behalf of the REACH Registry Investigators
- aFACT, French Alliance for Cardiovascular Trials, Département Hospitalo-Universitaire FIRE, Hôpital Bichat, Assistance Publique–Hôpitaux de Paris, Paris, FranceFACT, French Alliance for Cardiovascular Trials, Departement Hospitalo-Universitaire FIRE, Hopital Bichat, Assistance Publique–Hopitaux de Paris, Paris, France
- bHôpital Avicenne, Assistance Publique-hôpitaux de Paris, Bobigny, FranceHopital Avicenne, Assistance Publique-hopitaux de Paris, Bobigny, France
- cINSERM U1148, LVTS, Paris, FranceINSERM U1148, LVTS, Paris, France
- dDépartement de Cardiologie, Centre Hospitalier Universitaire de Nancy, Nancy, FranceDepartement de Cardiologie, Centre Hospitalier Universitaire de Nancy, Nancy, France
- eDuke Clinical Research Institute and Duke University Medical Center, Durham, North CarolinaDuke Clinical Research Institute and Duke University Medical Center, Durham, North Carolina
- fDepartment of Neurology, Asklepios Klinik Altona, Hamburg, GermanyDepartment of Neurology, Asklepios Klinik Altona, Hamburg, Germany
- gAtlanta VA Medical Center and Cardiology Division, Emory University School of Medicine, Atlanta, GeorgiaAtlanta VA Medical Center and Cardiology Division, Emory University School of Medicine, Atlanta, Georgia
- hSorbonne Université, ACTION Study Group, INSERM UMRS 1166, Institut de Cardiologie, Hôpital Pitié-Salpêtrière (AP-HP), Paris, FranceSorbonne Universite, ACTION Study Group, INSERM UMRS 1166, Institut de Cardiologie, Hopital Pitie-Salpetriere (AP-HP), Paris, France
- iKlinikum Ludwigshafen and Institut für Herzinfasrktforschung Ludwigshafen, Ludwigshafen, GermanyKlinikum Ludwigshafen and Institut fur Herzinfasrktforschung Ludwigshafen, Ludwigshafen, Germany
- jBrigham and Women’s Hospital and Harvard Medical School, Boston, MassachusettsBrigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts
- kImperial College, Royal Brompton Hospital, London, United KingdomkImperial College, Royal Brompton Hospital, London, United Kingdom
- ↵∗Address for correspondence:
Dr. Philippe Gabriel Steg, Cardiology, Hôpital Bichat, 46 rue Henri Huchard, 75018 Paris, France.
Background The COMPASS (Cardiovascular Outcomes for People Using Anticoagulation Strategies) trial found clinical benefit of low-dose rivaroxaban plus aspirin, but at the expense of increased bleeding risk in patients with stable vascular disease.
Objectives This study evaluated the balance of ischemic and bleeding risks according to the presence of ≥1 enrichment criteria in “COMPASS-eligible” patients.
Methods Key COMPASS selection criteria were applied to identify a COMPASS-eligible population (n = 16,875) from the REACH (REduction of Atherothrombosis for Continued Health) Registry of stable atherothrombotic patients. Ischemic outcome was the composite of cardiovascular death, myocardial infarction, or stroke. Bleeding outcome was serious bleeding (hemorrhagic stroke, hospitalization for bleeding, transfusion).
Results Patients were categorized according to the enrichment criteria: age >65 years (81.5%), diabetes (41.0%), moderate renal failure (40.2%), peripheral artery disease (33.7%), current smoker (13.8%), heart failure (13.3%), ischemic stroke (11.1%), and asymptomatic carotid stenosis (8.7%). Each criterion was associated with a consistent increase in ischemic and bleeding events, but no individual subgroup derived a more favorable trade-off. Patients with multiple criteria had a dramatic increase in ischemic risk (7.0% [95% confidence interval (CI): 5.6% to 8.7%], 12.5% [95% CI: 11.1% to 14.1%], 16.6% [95% CI: 14.7% to 18.6%], and 21.8% [95% CI: 19.9% to 23.9%] with 1, 2, 3, and ≥4 enrichment criteria, respectively), but a more modest absolute increase in bleeding risk (1.5% [95% CI: 0.9% to 2.1%], 1.8% [95% CI: 1.3% to 2.2%], 2.0% [95% CI: 1.5% to 2.6%], 3.2% [95% CI: 2.6% to 3.9%]).
Conclusions In a population of stable vascular patients at high risk of atherothrombotic events, the subset with multiple enrichment criteria had a greater absolute increase in ischemic than in bleeding risk and may be good candidates for low-dose rivaroxaban in addition to aspirin.
This analysis was in part funded by Bayer AG. The REACH Registry was originally funded by Sanofi and Bristol-Myers Squibb and the Waksman Foundation (until 2011) and is endorsed by the World Heart Federation. Editorial assistance in the preparation of the manuscript was funded by Fondation Assistance Publique−Hôpitaux de Paris, Paris, France. Dr. Darmon has received research grants from Abbott; and has received travel fees from Alvi Medica and Bayer. Dr. Sorbets has received personal fees and nonfinancial support from Bayer; and has received personal fees and nonfinancial support from Novartis, Servier, AstraZeneca, and Merck Sharp & Dohme. Dr. Ducrocq has received speaker and/or consulting fees from Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb, Janssen, Sanofi, and Terumo; has served on the Clinical Events Committee of Sanofi and Novo Nordisk; has served on the Data and Safety Monitoring Board of Abbott; and has received travel fees from AstraZeneca, Biotronik, Bayer, and Bristol-Myers Squibb. Dr. Abtan has received speaker and/or consulting fees from AstraZeneca, Abbott, and Bayer; and has received travel fees from AstraZeneca. Dr. Popovic has received consulting fees from AstraZeneca. Dr. Ohman has received research grants from Abiomed, Chiesi, and Portola; and has served as a consultant for 3D Communications, Abiomed, ACI Clinical, Biotie, Cara Therapeutics, Cardinal Health, Faculty Connection, Imbria, Impulse Medical, Janssen Pharmaceuticals, Medscape, Milestone Pharmaceuticals, and Xylocor. Dr. Röther has received honoraria from Bristol-Myers Squibb and Pfizer. Dr. Montalescot has received research grants to his institution or consulting/lecture fees from Abbott, Amgen, Actelion, AstraZeneca, Bayer, Boehringer Ingelheim, Boston Scientific, Bristol-Myers Squibb, Beth Israel Deaconess Medical, Brigham Women’s Hospital, Cardiovascular Research Foundation, Daiichi-Sankyo, Idorsia, Lilly, Europa, Elsevier, Fédération Française de Cardiologie, ICAN, Medtronic, Journal of the American College of Cardiology, Lead-Up, Menarini, Merck Sharp & Dohme, Novo Nordisk, Pfizer, Sanofi, Servier, The Mount Sinai School, TIMI Study Group, and WebMD. Dr. Zeymer has received grants and personal fees from AstraZeneca, Bristol-Myers Squibb, Daiichi-Sankyo, Novartis, and Eli Lilly; and has received personal fees from Bayer, Boehringer Ingelheim, The Medicines Company, and Sanofi. Dr. Bhatt has served on the Advisory Board of Cardax, Elsevier Practice Update Cardiology, Medscape Cardiology, PhaseBio, and Regado Biosciences; has served on the Board of Directors of Boston VA Research Institute, the Society of Cardiovascular Patient Care, and TobeSoft; has served as chair of the American Heart Association Quality Oversight Committee, NCDR-ACTION Registry Steering Committee, and VA CART Research and Publications Committee; has served on 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 the Population Health Research Institute; has received honoraria from the 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), Medtelligence/ReachMD (CME steering committees), 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); has served as Deputy Editor of Clinical Cardiology; has received 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; has received royalties from Elsevier (Editor, Cardiovascular Intervention: A Companion to Braunwald’s Heart Disease); has served as site co-investigator for Biotronik, Boston Scientific, St. Jude Medical (now Abbott), and Svelte; is a Trustee of the American College of Cardiology; and has performed unfunded research for FlowCo, Fractyl, Merck, Novo Nordisk, PLx Pharma, and Takeda. Dr. Steg has received research grants from Amarin, Bayer, Merck, Sanofi, and Servier; and has received speaking or consulting fees from Amarin, Amgen, AstraZeneca, Bayer/Janssen, Boehringer Ingelheim, Bristol-Myers Squibb, Idorsia, Lilly, Merck, Novartis, Novo Nordisk, Pfizer, Regeneron, Sanofi, and Servier. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
Listen to this manuscript's audio summary by Editor-in-Chief Dr. Valentin Fuster on JACC.org.
- Received April 9, 2019.
- Accepted April 16, 2019.
- 2019 American College of Cardiology Foundation
This article requires a subscription or purchase to view the full text. If you are a subscriber or member, click Login or the Subscribe link (top menu above) to access this article.