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CC BY 4.0 · TH Open 2022; 06(03): e177-e183
DOI: 10.1055/s-0042-1750379
Original Article

Rivaroxaban Plus Aspirin for Extended Thromboprophylaxis in Acutely Ill Medical Patients: Insights from the MARINER Trial

Alex C. Spyropoulos 
1   The Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, The Feinstein Institute for Medical Research, New York, New York, United States
2   Department of Medicine, Anticoagulation and Clinical Thrombosis Services, Northwell Health at Lenox Hill Hospital, New York, New York, United States
,
Mark Goldin
3   Northwell Health, Great Neck, New York, United States
,
Walter Ageno
4   Department of Medicine and Surgery, University of Insubria, Varese, Italy
5   University of Insubria, Varese, Italy
,
Gregory W. Albers
6   Stanford Stroke Center, Stanford Medical Center, Stanford University, Palo Alto, California, United States
,
C. Gregory Elliott
7   Department of Medicine, University of Utah and Intermountain Healthcare, Salt Lake City, Utah, United States
,
William R. Hiatt
8   Division of Cardiology, University of Colorado School of Medicine
9   CPC Clinical Research, Aurora, Colorado, United States
,
Jonathan L. Halperin
10   Cardiovascular Institute, Mount Sinai Medical Center, New York, New York, United States
,
Gregory Maynard
11   University of California at Davis, Sacramento, California, United States
,
P. Gabriel Steg
12   Université de Paris, Assistance Publique–Hôpitaux de Paris, and INSERM U-1148, Paris, France
,
Jeffrey I. Weitz
13   McMaster University
14   The Thrombosis and Atherosclerosis Research Institute, Hamilton, Ontario, Canada
,
Theodore E. Spiro
15   Bayer US, LLC, Whippany, New Jersey, United States
,
Wentao Lu
16   Cardiovascular Clinical Development, Janssen Research and Development, LLC, Raritan, New Jersey, United States
,
Jessica Marsigliano
16   Cardiovascular Clinical Development, Janssen Research and Development, LLC, Raritan, New Jersey, United States
,
Gary E. Raskob
17   Hudson College of Public Health, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States
,
Elliot S. Barnathan 
16   Cardiovascular Clinical Development, Janssen Research and Development, LLC, Raritan, New Jersey, United States
› Author Affiliations Funding/Acknowledgments Janssen Research & Development LLC sponsored the MARINER study.
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Abstract

Background The MARINER trial evaluated whether postdischarge thromboprophylaxis with rivaroxaban could reduce the primary outcome of symptomatic venous thromboembolism (VTE) or VTE-related death in acutely ill medical patients at risk for VTE. Although aspirin use was not randomized, approximately half of the enrolled patients were receiving aspirin at baseline. We hypothesized that thromboprophylaxis with once-daily rivaroxaban (10 mg or, if creatinine clearance was 30–49 mL/min, 7.5 mg) plus aspirin (R/A) would be superior to placebo without aspirin (no thromboprophylaxis [no TP]).

Methods We compared the primary and major secondary outcomes in the intention-to-treat population in four subgroups defined at baseline: (1) R/A (N = 3,159); (2) rivaroxaban alone (N = 2,848); (3) aspirin alone (N = 3,046); and (4) no TP (N = 2,966). Major bleeding (MB) and nonmajor clinically relevant (NMCR) bleeding were assessed in the safety population on treatment plus 2 days.

Results Patients on R/A had reduced symptomatic VTE and VTE-related death compared with no TP (0.76 vs 1.28%, p = 0.042), and experienced less symptomatic VTE and all-cause mortality (p = 0.005) and all-cause mortality alone (p = 0.01) compared with no TP. Event incidences for rivaroxaban alone (0.91%) or aspirin alone (0.92%) were similar. MB was low in all groups but lowest in the no TP group. NMCR bleeding was increased with R/A compared with no TP (p = 0.009).

Limitations Aspirin use was not randomized.

Conclusion Extended postdischarge thromboprophylaxis with R/A was associated with less symptomatic VTE and VTE-related death compared with no TP in previously hospitalized medical patients at risk for VTE. NMCR bleeding was increased with R/A compared with no TP. These post hoc findings need confirmation in a prospective trial.

Keywords

aspirin - combined modality therapy - hospitalization - rivaroxaban - venous thromboembolism

Author Contributions

All authors have contributed equally to the manuscript: (1) conception and design of the work, and analysis and interpretation of the data; (2) drafting the work or revising it critically for important intellectual content including: Introduction, Methods, Results, and Discussion; (3) final approval of the version to be published; and (4) agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.




Publication History

Received: 09 March 2022

Accepted: 25 April 2022

Article published online:
11 July 2022

© 2022. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

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