Author + information
- Received April 8, 2020
- Revision received April 17, 2020
- Accepted April 25, 2020
- Published online June 22, 2020.
- Alex C. Spyropoulos, MDa,∗ (, )@AlexSpyropoul,
- Walter Ageno, MDb,
- Gregory W. Albers, MDc,
- C. Gregory Elliott, MDd,
- Jonathan L. Halperin, MDe,
- William R. Hiatt, MDf,g,
- Gregory A. Maynard, MDh,
- P. Gabriel Steg, MDi,j,
- Jeffrey I. Weitz, MDk,
- Wentao Lu, PhDl,
- Theodore E. Spiro, MDm,
- Elliot S. Barnathan, MDl and
- Gary. E. Raskob, PhDn
- aThe Donald and Barbara Zucker School of Medicine and Hofstra/Northwell, The Feinstein Institute for Medical Research, and Department of Medicine, Anticoagulation and Clinical Thrombosis Services Northwell Health at Lenox Hill Hospital, New York, New York
- bDepartment of Medicine and Surgery, University of Insubria, Varese, Italy
- cStanford Stroke Center, Stanford University Medical Center, Stanford, California
- dDepartment of Medicine, Intermountain Medical Center and the University of Utah, Salt Lake City, Utah
- eThe Cardiovascular Institute, Mount Sinai Medical Center, New York, New York
- fUniversity of Colorado School of Medicine, Division of Cardiology, Aurora, Colorado
- gCPC Clinical Research, Aurora, Colorado
- hUniversity of California, Davis, Sacramento, California
- iUniversité de Paris, Assistance Publique-Hôpitaux de Paris, INSERM U-1148, Paris, France
- jImperial College, Royal Brompton Hospital, London, United Kingdom
- kMcMaster University and the Thrombosis and Atherosclerosis Research Institute, Hamilton, Ontario, Canada
- lJanssen Research & Development, LLC, Raritan, New Jersey
- mThrombosis and Hematology Therapeutic Area, Clinical Development, Pharmaceuticals, Bayer U.S. LLC, Whippany, New Jersey
- nHudson College of Public Health, The University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma
- ↵∗Address for correspondence:
Dr. Alex C. Spyropoulos, The Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, The Feinstein Institute for Medical Research, and Department of Medicine, Anticoagulation and Clinical Thrombosis Services, Northwell Health at Lenox Hill Hospital, 130 East 77th Street, New York, New York 10075.
Background Hospitalized acutely ill medical patients are at risk for fatal and major thromboembolic events. Whether use of extended-duration primary thromboprophylaxis can prevent such events is unknown.
Objectives The purpose of this study was to evaluate whether extended-duration rivaroxaban reduces the risk of venous and arterial fatal and major thromboembolic events without significantly increasing major bleeding in acutely ill medical patients after discharge.
Methods MARINER (A Study of Rivaroxaban [JNJ-39039039] on the Venous Thromboembolic Risk in Post-Hospital Discharge Patients) studied acutely ill medical patients with additional risk factors for venous thromboembolism (VTE). Medically ill patients with a baseline creatinine clearance ≥50 ml/min were randomized in a double-blind fashion to rivaroxaban 10 mg or placebo daily at hospital discharge for 45 days. Exploratory efficacy analyses were performed with the intent-to-treat population including all data through day 45. Time-to-event curves were calculated using the Kaplan-Meier method. A blinded independent committee adjudicated all clinical events.
Results In total, 4,909 patients were assigned to rivaroxaban and 4,913 patients to placebo. The mean age was 67.8 years, 55.5% were men, mean baseline creatinine clearance was 87.8 ml/min, and mean duration of hospitalization was 6.7 days. The pre-specified composite efficacy endpoint (symptomatic VTE, myocardial infarction, nonhemorrhagic stroke, and cardiovascular death) occurred in 1.28% and 1.77% of patients in the rivaroxaban and placebo groups, respectively (hazard ratio: 0.72; 95% confidence interval: 0.52 to 1.00; p = 0.049), whereas major bleeding occurred in 0.27% and 0.18% of patients in the rivaroxaban and placebo groups, respectively (hazard ratio: 1.44; 95% confidence interval: 0.62 to 3.37; p = 0.398).
Conclusions Extended-duration rivaroxaban in hospitalized medically ill patients resulted in a 28% reduction in fatal and major thromboembolic events without a significant increase in major bleeding. (A Study of Rivaroxaban [JNJ-39039039] on the Venous Thromboembolic Risk in Post-Hospital Discharge Patients [MARINER]; NCT02111564)
The MARINER study is sponsored by Janssen Research & Development LLC. Dr. Spyropoulos has served as a consultant for Janssen Research & Development LLC, Bayer, Portola, Boehringer Ingelheim, and Bristol-Myers Squibb; has received research support from Boehringer Ingelheim and Janssen; has served on an Advisory Board for Daiichi-Sankyo; and has received a stipend from the ATLAS group. Dr. Ageno has received research grant support from Bayer; and has received honoraria for Advisory Board activity from Bayer, Boehringer Ingelheim, Daiichi-Sankyo, Sanofi, Portola, Janssen, and Aspen. Dr. Albers has served as a consultant for Bayer and Janssen Research and Development, LLC. Dr. Elliott has served as a consultant for Bayer and Janssen Research and Development, LLC; and has received honoraria from the University of Cincinnati and Spectrum Health. Dr. Halperin has served as a consultant for Janssen Research & Development LLC, Johnson & Johnson, Ortho-McNeil-Janssen, Bayer, Abbott, Boehringer Ingelheim, National Institute of Health, and the ATLAS group. Dr. Hiatt has received research grants from Janssen Research & Development LLC, Bayer, Amgen, and the National Institutes of Health. Dr. Maynard has served on the Executive Committee of the MARINER trial for Janssen Research & Development LLC. Dr. Steg has received research grants from Amarin, Bayer, Sanofi, and Servier; and has served on clinical trials and served as a speaker or consultant for Amarin, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Idorsia, Novartis, Pfizer, Sanofi, and Servier. Dr. Weitz has received consultancy or honoraria fees from Janssen Research & Development LLC, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi-Sankyo, Ionis, Merck, Novartis, Pfizer, Portola, Anthos, and Servier. Drs. Lu and Barnathan are employees and shareholders of Janssen Research & Development LLC. Dr. Spiro was an employee of Bayer U.S. LLC. Dr. Raskob has served as a consultant for Janssen Research & Development LLC, Bayer, Bristol-Myers Squibb, Daiichi-Sankyo, Boehringer Ingelheim, Eli Lilly, Pfizer, Portola, Novartis, Anthos, Tetherex, and XaTek. Samuel Z. Goldhaber, MD served as Guest Associate Editor for this paper.
The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the JACC author instructions page.
- Received April 8, 2020.
- Revision received April 17, 2020.
- Accepted April 25, 2020.
- 2020 The Authors