Extended rivaroxaban prophylaxis following a medical inpatient stay does not provide a net benefit (MARINER)

Reference

Spyropoulos AC, Ageno W, Albers GW, et al, for the MARINER Investigators. Rivaroxaban for thromboprophylaxis after hospitalization for medical illness. N Engl J Med 2018;379(12):1118-1127.

Synopsis

Although current guidelines do not recommend extended thromboprophylaxis following hospitalization for an acute medical illness, the slightly more favorable risk profile of the newer direct oral anticoagulants, such as rivaroxaban, may have changed that balance in favor of net benefit. These authors identified patients who had recently been hospitalized for heart failure, acute respiratory illness, acute stroke, or acute infectious or inflammatory conditions who received thromboprophylaxis with heparin (unfractionated or low molecular weight) during their hospital stay. Patients at high risk for VTE based on the validated IMPROVE risk score and those at moderate risk with an elevated d-dimer level (N = 12,019) were randomized at discharge to rivaroxaban 10 mg once daily (7.5 mg once daily if creatinine clearance was 30 to 50 mL/min) or matching placebo. All patients were at least 40 years old, had been hospitalized for 3 to 10 days, and if hospitalized for heart failure had an ejection fraction of less than 45%. Patients were contacted several times during the study and asked about signs or symptoms of thromboembolism or bleeding. Outcomes were adjudicated by a committee masked to treatment assignment. Although the authors estimated that they would need 8000 patients to see the 161 events needed for their sample size, they increased the size of the trial and still had only 116 events by the end of the trial. The mean age of included patients was 70 years, 36% were 75 years or older, and 52% were men. Groups were balanced at the start of the study, and analysis was by intention to treat. Overall, there was no net benefit for the rivaroxaban group. There were no significant differences in the primary prespecified outcomes of symptomatic VTE or VTE-related death (hazard ratio [HR] 0.76; 95% CI 0.52 - 1.09), major bleeding (HR 1.88; 0.84 - 4.23), or all-cause mortality. As expected, the trends favored fewer thromboembolic events but more bleeds for the rivaroxaban group.