Benefit–Risk Assessment of Rivaroxaban for Extended Thromboprophylaxis After Hospitalization for Medical Illness

BACKGROUND: Venous thromboembolism (VTE) often occurs after hospitalization in medically ill patients, but the population benefit–risk of extended thromboprophylaxis remains uncertain. METHODS AND RESULTS: The MARINER (Medically Ill Patient Assessment of Rivaroxaban Versus Placebo in Reducing Post‐Discharge Venous Thrombo‐Embolism Risk) study (NCT02111564) was a randomized double‐blind trial that compared thromboprophylaxis with rivaroxaban 10 mg daily versus placebo for 45 days after hospital discharge in medically ill patients with a creatinine clearance ≥50 mL/min. The benefit–risk balance in this population was quantified by calculating the between‐treatment rate differences in efficacy and safety end points per 10 000 patients treated. Clinical characteristics of the study population were consistent with a hospitalized medical population at risk for VTE. Treating 10 000 patients with rivaroxaban resulted in 32.5 fewer symptomatic VTE and VTE‐related deaths but was associated with 8 additional major bleeding events. The treatment benefit was driven by the prevention of nonfatal symptomatic VTE (26 fewer events). There was no between‐treatment difference in the composite of critical site or fatal bleeding. CONCLUSIONS: Extending thromboprophylaxis with rivaroxaban for 45 days after hospitalization provides a positive benefit–risk balance in medically ill patients at risk for VTE who are not at high risk for bleeding. REGISTRATION: URL: https://clinicaltrials.gov/; Unique identifier: NCT02111564.