Patients hospitalized for an acute medical illness who receive extended-duration prophylaxis with rivaroxaban at discharge may have a lower risk for fatal and major thromboembolic events, according to a recent industry-funded study.
Researchers used data from the MARINER trial, which was funded by Janssen Research and Development, to determine whether medically ill patients with additional risk factors for venous thromboembolism (VTE) had a lower risk if they received prophylaxis with rivaroxaban for an extended period after hospitalization. Patients were randomly assigned to receive rivaroxaban, 10 mg daily, or placebo at hospital discharge for 45 days if they were at least 40 years of age, had been hospitalized for an acute medical illness for at least three and no more than 10 consecutive days, and had a baseline creatinine clearance of 50 mL/min or more.
The efficacy outcome, a prespecified secondary end point, was a composite of symptomatic VTE, myocardial infarction, nonhemorrhagic stroke, and cardiovascular death. The main safety outcome, major bleeding, was defined as fatal bleeding, bleeding into a critical organ, or bleeding that led to a decrease of at least 2 g/dL of hemoglobin or transfusion of at least 2 units of blood. The results of the study were published June 22 by the Journal of the American College of Cardiology.
The intention-to-treat population included 4,909 patients in the MARINER trial assigned to rivaroxaban and 4,913 assigned to placebo. Mean patient age was 67.8 years, 55.5% were men, and mean baseline creatinine clearance was 87.8 mL/min. Mean hospitalization duration was 6.7 days. Most patients (96.5%) were white. The most common diagnosis at admission was heart failure with reduced ejection fraction of 45% or lower, which was present in 37.2% of patients. Overall, 1.28% of patients in the rivaroxaban group and 1.77% of patients in the placebo group experienced the composite efficacy end point (hazard ratio, 0.72; 95% CI, 0.52 to 1.00; P=0.049). In the safety analysis, which included 4,890 patients each in the rivaroxaban and placebo groups, 0.27% and 0.18%, respectively, experienced major bleeding (hazard ratio, 1.44; 95% CI, 0.62 to 3.37; P=0.398).
The authors noted that their study should be considered exploratory because the MARINER trial did not meet its primary efficacy end point. In addition to other limitations, they also pointed out that approximately 50% of the study population was taking aspirin at baseline. However, they concluded that extended-duration thromboprophylaxis with low-dose rivaroxaban started after discharge in patients hospitalized for a medical illness significantly reduced the combined risk for fatal and major thromboembolic events with no significant increase in major bleeding. The benefit appeared to start after the first week of treatment and continued through the end of the study at 45 days, they said. “These data suggest that in properly selected patients at risk for VTE and at low risk for bleeding, that extended-duration rivaroxaban at 10 mg has a favorable benefit risk profile,” the authors wrote.
The author of an accompanying editorial noted that both rivaroxaban in this substudy of the MARINER trial and betrixaban in a substudy of the APEX trial were associated with a reduction in overall cardiovascular events. “The findings with rivaroxaban and betrixaban suggest that we should abandon a silo approach for the prevention of venous or arterial thrombosis and promote a holistic strategy to vascular disease,” the editorialist wrote. However, he also cautioned that it will be difficult to put the findings of these trials into practice. “The American Society of Hematology guidelines recommend against the use of extended-duration anticoagulant prophylaxis after hospital discharge,” he wrote. “Those physicians who advocate for out-of-hospital VTE prophylaxis will have to convince their colleagues on the hospital formulary committees.”