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

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.
Competing Interests: Conflict of Interest Alex C. Spyropoulos: Janssen Research & Development LLC, Bayer, Portola, Boehringer Ingelheim, Daiichi Sankyo, ATLAS group; Mark Goldin: Janssen Research & Development LLC; Walter Ageno: Janssen Research & Development LLC, Bayer, Portola, Daiichi Sankyo, Aspen, BMS, Pfizer, Sanofi, Leo Pharma; Gregory W. Albers: Janssen Research & Development LLC, Bayer; C. Greg Elliott: Janssen Research & Development LLC, Bayer; Jonathan L. Halperin: Janssen Research & Development LLC, Abbott, Bayer, Boehringer Ingelheim, National Institute of Health, ATLAS group, Johnson & Johnson, Ortho-McNeil-Janssen; William R. Hiatt: Janssen Research & Development LLC, Bayer, NIH; Gregory Maynard: Janssen Research & Development LLC; P. Gabriel Steg: Janssen Research & Development LLC, Bayer, Merck, Sanofi, Servier, Amarin, Amgen, Bristol-Myers Squibb, Boehringer Ingelheim, Pfizer, Novartis, Regeneron, Lilly, AstraZeneca, Idorsia, Novo-Nordisk; Jeffrey I. Weitz: Janssen Research & Development LLC, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi-Sankyo, Ionis, Merck, Novartis, Pfizer, Portola, Anthos, Servier; Theodore E. Spiro: Bayer U.S. LLC; Wentao Lu, Janssen Research and Development LLC; Jessica Marsigliano, Janssen Research and Development LLC; Gary E. Raskob: Janssen Research & Development LLC, Bayer, BMS, Daiichi Sankyo, Boehringer Ingelheim, Eli Lilly, Pfizer, Portola, Novartis, Anthos, Tetherex; Elliot S. Barnathan: Janssen Research & Development LLC.
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