How Extending Rivaroxaban After COVID-19 Hospitalization

Patients who are hospitalized with COVID-19 have elevated rates of postdischarge thrombotic events, but uncertainty exists about whether Thromboprophylaxis should continue beyond the hospital stay. In a recent phase 3 trial, continuing Thromboprophylaxis after patients hospitalized with COVID-19 were discharged reduced major and fatal thromboembolic events without increasing major bleeding.

The trial randomized 320 patients hospitalized with COVID-19 at centers in Brazil to 10-mg/d Rivaroxaban or no anticoagulation for 35 days after discharge. All patients received Thromboprophylaxis while hospitalized and were at high risk of venous Thromboembolism at discharge.

At day 35, about 3% of the Rivaroxaban group and about 9% of the control group had an efficacy outcome event, a composite of venous and arterial thromboembolism and cardiovascular death. No major bleeding occurred in either group. Two patients in the Rivaroxaban group experienced allergic reactions. The findings appeared in The Lancet.

Thrombotic events complicate COVID-19 at higher rates than previously observed in other comparable clinical situations, such as acute distress respiratory syndrome not related to SARS-CoV-2.

Prophylactic use of parenteral anticoagulants during hospitalisation is recommended, and there is emerging consensus about the role of in-hospital heparin as primary thromboprophylaxis.

There is no consensus on the use of extended thromboprophylaxis beyond the hospital stay. Multiple studies of post-discharge patients with COVID-19 show incidences of symptomatic venous thromboembolism ranging from below 1% to 2·5%.

In the largest prospective registry, which included 4906 post-discharge patients with COVID-19, the incidence of the primary endpoint of venous thromboembolism, arterial thromboembolism, or all-cause death was 7·13%, and was 46% lower in patients prescribed post-discharge prophylactic anticoagulation.

Extended venous thromboembolism prophylaxis after hospitalisation for medically ill (non-COVID-19) patients was previously assessed. The MARINER trial evaluated rivaroxaban 10 mg or 7·5 mg (if creatinine clearance <50mL/min) once per day versus placebo for 45 days after hospital discharge in 12 019 medically ill patients. Although the trial did not achieve superiority on the primary endpoint of symptomatic or fatal venous thromboembolism, there was a statistically significant 56% reduction in the relative risk of the prespecified outcome of isolated symptomatic venous thromboembolism, a 27% relative risk reduction of symptomatic venous thromboembolism and all-cause death, and a 28% relative risk reduction in major and fatal thromboembolic events. There was no statistically significant increase in the rate of major bleeding.

Findings

From Oct 8, 2020, to June 29, 2021, 997 patients were screened. Of these patients, 677 did not meet eligibility criteria; the remaining 320 patients were enrolled and randomly assigned to receive rivaroxaban (n=160 [50%]) or no anticoagulation (n=160 [50%]). All patients received thromboprophylaxis with standard doses of heparin during hospitalisation. 165 (52%) patients were in the intensive care unit while hospitalised. 197 (62%) patients had an IMPROVE score of 2–3 and elevated D-dimer levels and 121 (38%) had a score of 4 or more. Two patients (one in each group) were lost to follow-up due to withdrawal of consent and not included in the intention-to-treat primary analysis. The primary efficacy outcome occurred in five (3%) of 159 patients assigned to rivaroxaban and 15 (9%) of 159 patients assigned to no anticoagulation (relative risk 0·33, 95% CI 0·12–0·90; p=0·0293). No major bleeding occurred in either study group. Allergic reactions occurred in two (1%) patients in the rivaroxaban group.