Author + information
- Received August 13, 2018
- Revision received October 3, 2018
- Accepted October 8, 2018
- Published online January 14, 2019.
- Andre Lamy, MDa,b,c,d,∗ (, )@McMasterU,
- John Eikelboom, MBBSa,e,
- Tej Sheth, MDa,e,
- Stuart Connolly, MDa,e,
- Jackie Bosch, PhDa,
- Keith A.A. Fox, MBChBf,
- Jun Zhu, MDg,
- Eva Lonn, MDa,d,e,
- Gilles Dagenais, MDh,
- Petr Widimsky, MDi,
- Kelly R.H. Branch, MDj,
- Deepak L. Bhatt, MDk,
- Zhe Zheng, MDg,
- Zbynek Straka, MDi,†,
- Francois Dagenais, MDl,
- Ye Kong, MDm,
- Tamara Marsden, MSa,
- Shun Fu Lee, PhDa,
- Ingrid Copland, CCRAa and
- Salim Yusuf, DPhila,d,e
- aPopulation Health Research Institute, McMaster University, Hamilton, Ontario, Canada
- bCADENCE Research Group, Hamilton Health Sciences, Hamilton, Ontario, Canada
- cDepartment of Surgery, McMaster University, Hamilton, Ontario, Canada
- dDepartment of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Ontario, Canada
- eDepartment of Medicine, McMaster University, Hamilton, Ontario, Canada
- fCentre for Cardiovascular Science, University of Edinburgh, Edinburgh, United Kingdom
- gFuWai Hospital, Beijing, China
- hInstitut Universitaire de Cardiologie et de Pnemologie de Québec, Quebec City, Quebec, Canada
- iCardiocenter, University Hospital Kralovske Vinohrady and Third Faculty of Medicine, Charles University, Prague, Czech Republic
- jUniversity of Washington Medical Center, Seattle, Washington
- kBrigham and Women’s Hospital Heart and Vascular Center, Harvard Medical School, Boston, Massachusetts
- lQuebec Heart and Lung University Institute, Laval University, Quebec City, Quebec, Canada
- mShanghai Chest Hospital Affiliated with Shanghai Jiao Tong University, Shanghai, China
- ↵∗Address for correspondence:
Dr. Andre Lamy, DBCVSRI C1-112, 237 Barton Street, East Hamilton, Ontario L8L 2X2, Canada.
Background Patients with recent coronary artery bypass graft (CABG) surgery are at risk for early graft failure, which is associated with a risk of myocardial infarction and death. In the COMPASS (Cardiovascular OutcoMes for People Using Anticoagulation StrategieS) trial, rivaroxaban 2.5 mg twice daily plus aspirin 100 mg once daily compared with aspirin 100 mg once daily reduced the primary major adverse cardiovascular events (MACE) outcome of cardiovascular death, stroke, or myocardial infarction. Rivaroxaban 5 mg twice daily alone did not significantly reduce MACE.
Objectives This pre-planned substudy sought to determine whether the COMPASS treatments are more effective than aspirin alone for preventing graft failure and MACE after CABG surgery.
Methods The substudy randomized 1,448 COMPASS trial patients 4 to 14 days after CABG surgery to receive the combination of rivaroxaban plus aspirin, rivaroxaban alone, or aspirin alone. The primary outcome was graft failure, diagnosed by computed tomography angiogram 1 year after surgery.
Results The combination of rivaroxaban and aspirin and the regimen of rivaroxaban alone did not reduce the graft failure rates compared with aspirin alone (combination vs. aspirin: 113 [9.1%] vs. 91 [8.0%] failed grafts; odds ratio [OR]: 1.13; 95% confidence interval [CI]: 0.82 to 1.57; p = 0.45; rivaroxaban alone vs. aspirin: 92 [7.8%] vs. 92 [8.0%] failed grafts; OR: 0.95; 95% CI: 0.67 to 1.33; p = 0.75). Compared with aspirin, the combination was associated with fewer MACE (12 [2.4%] vs. 16 [3.5%]; hazard ratio [HR]: 0.69; 95% CI: 0.33 to 1.47; p = 0.34), whereas rivaroxaban alone was not (16 [3.3%] vs. 16 [3.5%]; HR: 0.99, CI: 0.50 to 1.99; p = 0.98). There was no fatal bleeding or tamponade within 30 days of randomization.
Conclusions The combination of rivaroxaban 2.5 mg twice daily plus aspirin or rivaroxaban 5 mg twice daily alone compared with aspirin alone did not reduce graft failure in patients with recent CABG surgery, but the combination of rivaroxaban 2.5 mg twice daily plus aspirin was associated with similar reductions in MACE, as observed in the larger COMPASS trial. (Cardiovascular OutcoMes for People Using Anticoagulation StrategieS [COMPASS]; NCT01776424)
↵† Dr. Straka is deceased.
This substudy was part of the COMPASS study, which was supported by grants from Bayer. Dr. Eikelboom has received grants and personal fees from Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Pfizer, Daiichi-Sankyo, Janssen, AstraZeneca, Eli Lilly, GlaxoSmithKline, and Sanofi. Dr. Connolly has received grants from Bayer; and has received personal fees from Bristol-Myers Squibb, Pfizer, Portola, Boehringer Ingelheim, Servier, Daiichi-Sankyo, Medtronic, and Abbott. Dr. Bosch has received grants from and is on the advisory board of Bayer. Dr. Fox has received grants and personal fees from Bayer, Janssen, and AstraZeneca; has received personal fees from Sanofi and Regeneron; and has served as a consultant to Vereon. Dr. Zhu has received personal fees from Bayer, Boehringer Ingelheim, and Sanofi. Dr. Lonn has received personal fees from Bayer, Amgen, Sanofi, Novartis, and Servier; is on the advisory board of Bayer, Amgen, and Sanofi; and has received lecture honoraria from Bayer, Amgen, Sanofi, and Novartis. Dr. Widimsky is on the advisory board of Bayer. Dr. Branch has received grants from Bayer and Astellas; is on the advisory board of Janssen and Bayer; and has received other fees from Janssen. Dr. Bhatt is on the advisory boards of Cardax, Elsevier Practice Update Cardiology, Medscape Cardiology, and Regado Biosciences; is on the board of directors of Boston VA Research Institute, Society of Cardiovascular Patient Care, and TobeSoft; is Chair of the American Heart Association Quality Oversight Committee; is on the data monitoring committees of the Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute, for the PORTICO trial, funded by St. Jude Medical, now Abbott), Cleveland Clinic, Duke Clinical Research Institute, Mayo Clinic, Mount Sinai School of Medicine (for the ENVISAGE trial, funded by Daiichi-Sankyo), and Population Health Research Institute; has received honoraria from the American College of Cardiology (as Senior Associate Editor of Clinical Trials and News, ACC.org; and as vice-chair of the ACC Accreditation Committee), Baim Institute for Clinical Research ([formerly Harvard Clinical Research Institute] for membership on the RE-DUAL PCI clinical trial steering committee funded by Boehringer Ingelheim), Belvoir Publications (as Editor-in-Chief of Harvard Heart Letter), Duke Clinical Research Institute (for membership on clinical trial steering committees), HMP Global (as Editor-in-Chief of the Journal of Invasive Cardiology), Journal of the American College of Cardiology (as Guest Editor and Associate Editor), Population Health Research Institute (for membership on the COMPASS operations committee, the publications committee, and the steering committee; and as USA national co-leader, funded by Bayer), Slack Publications (as Chief Medical Editor of Cardiology Today’s Intervention), Society of Cardiovascular Patient Care (as Secretary/Treasurer), and WebMD (for membership on the CME steering committees); is the Deputy Editor of Clinical Cardiology; is the Chair of the NCDR-ACTION Registry Steering Committee and the VA CART Research and Publications Committee; 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 (as editor of Cardiovascular Intervention: A Companion to Braunwald’s Heart Disease); is 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 conducted unfunded research for FlowCo, Merck, Novo Nordisk, PLx Pharma, and Takeda. Dr. Yusuf has received grants and personal fees from Bayer, Boehringer Ingelheim, AstraZeneca, Bristol-Myers Squibb, and Cadila; and has received consultant and speaker fees and travel expenses from Bayer. 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 August 13, 2018.
- Revision received October 3, 2018.
- Accepted October 8, 2018.
- 2019 American College of Cardiology Foundation
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