Postdischarge prophylaxis with rivaroxaban cuts thromboembolic events in medically ill patients

Extended-duration thromboprophylaxis with low-dose rivaroxaban in at-risk medically ill patients discharged from the hospital significantly reduces fatal and major thromboembolic events, including symptomatic venous thromboembolism (VTE), myocardial infarction (MI), nonhaemorrhagic stroke, and cardiovascular (CV) death, with no significant increase in major bleeding, compared with placebo, a study has shown.

“Treatment with rivaroxaban 10 mg once daily for up to 45 days beyond discharge of patients at higher risk of thromboembolism and lower risk of bleeding reduces the incidence of fatal and major thromboembolism without increasing major bleeding,” the researchers said.

This study analysed acutely ill medical patients (mean age, 67.8 years; 55.5 percent men; baseline creatinine clearance, 87.8 ml/min) with additional risk factors for VTE. Those with a baseline creatinine clearance ≥50 ml/min were randomly assigned to rivaroxaban 10 mg (n=4,909) or placebo (n=4,913) daily at hospital discharge for 45 days.

The researchers carried out exploratory efficacy analyses of the intent-to-treat population including all data through day 45 and calculated time-to-event curves using the Kaplan-Meier method. A blinded independent committee adjudicated all clinical events.

The mean duration of hospitalization was 6.7 days. The prespecified composite efficacy endpoint of symptomatic VTE, MI, nonhaemorrhagic stroke, and CV death occurred in 1.28 percent of patients in the rivaroxaban group and 1.77 percent in the placebo group (hazard ratio [HR], 0.72, 95 percent confidence interval [CI], 0.52–1.00; p=0.049). [J Am Coll Cardiol 2020;75:3140-3147]

On the other hand, major bleeding occurred in 0.27 percent and 0.18 percent of patients in the rivaroxaban and placebo groups, respectively (HR, 1.44 ,95 percent CI, 0.62–3.37; p=0.398).

“Although exploratory, our analysis suggests that extended thromboprophylaxis with rivaroxaban in medically ill patients may lead to reductions in arterial thromboembolic events, primarily ischaemic stroke, as well as a reduction in symptomatic VTE,” the researchers said.

These results were consistent with those of the APEX trial, which found a ∼30-percent decrease in fatal and irreversible ischaemic events without an increase in fatal or intracranial haemorrhage, as well as a ∼50-percent reduction in ischaemic stroke with betrixaban compared with placebo. [Circulation 135:648-655; J Am Heart Assoc 2017;6.e006015; N Engl J Med 375:534-544]

Additionally, in a recent pooled analysis of both the MARINER and MAGELLAN trials of extended thromboprophylaxis with 10-mg rivaroxaban, results showed a 22-percent reduction in all-cause mortality and major thromboembolic events without an increase in critical site or fatal bleeding. [Circulation 2019;140:A12863]

“Our findings may have important implications for the population of medically ill patients now that rivaroxaban is approved for extended posthospital discharge thromboprophylaxis in at-risk medically ill patients in the US,” the researchers said.

“Prospective studies of patients hospitalized with coronavirus disease-2019 pneumonia are needed to confirm the benefit and safety of extended antithrombotic therapy in that specific subset of medically ill patients,” they added.