Post-Discharge Prophylaxis With Rivaroxaban Reduces Fatal and Major Thromboembolic Events in Medically Ill Patients

Alex C Spyropoulos, Walter Ageno, Gregory W Albers, C Gregory Elliott, Jonathan L Halperin, William R Hiatt, Gregory A Maynard, P Gabriel Steg, Jeffrey I Weitz, Wentao Lu, Theodore E Spiro, Elliot S Barnathan, Gary E Raskob, Alex C Spyropoulos, Walter Ageno, Gregory W Albers, C Gregory Elliott, Jonathan L Halperin, William R Hiatt, Gregory A Maynard, P Gabriel Steg, Jeffrey I Weitz, Wentao Lu, Theodore E Spiro, Elliot S Barnathan, Gary E Raskob

Abstract

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).

Keywords: hospitalized; major bleeding; medically ill; rivaroxaban; thromboembolic events.

Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.

Figures

Graphical abstract
Graphical abstract
Central Illustration
Central Illustration
Major Efficacy and Safety Outcomes Over Time (A) Time to first occurrence of composite: venous thromboembolism, myocardial infarction, nonhemorrhagic stroke, and cardiovascular death up to day 45 (rivaroxaban 10 mg daily vs. placebo; intention to treat). Includes all data from randomization to day 45 (inclusive). Patients who do not have events are censored on the minimum of last visit before or on death or day 45. (B) Time to first occurrence of major bleeding on-treatment (rivaroxaban 10 mg daily vs. placebo; safety population). On-treatment includes all data from randomization to 2 days after the last dose of the study drug (inclusive). Subjects who do not have events are censored on the minimum of last visit before or on death, or last dose +2 days. CI = confidence interval; HR = hazard ratio.

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Source: PubMed

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