Extending thromboprophylaxis with prophylactic-dose rivaroxaban at the time of discharge from the hospital in high-risk COVID-19 patients improves their prognosis, according to the recently reported MICHELLE Trial.

The multicenter MICHELLE (Medically Ill Hospitalized Patients For COVID-19 Thrombosis Extended Prophylaxis With Rivaroxaban Therapy) trial was designed as an open-label, randomized trial. Conducted at 14 centers in Brazil, it involved 320 patients, aged 57 years (average), hospitalized with COVID-19 at increased risk for venous thromboembolism (VTE). The risk was defined by an  International Medical Prevention Registry on Venous Thromboembolism [IMPROVE] venous thromboembolism [VTE] score of ≥4 or 2-3 with a D-dimer >500 ng/mL. The trial excluded patients at risk for bleeding such as those with thrombocytopenia or severe renal failure, gastric ulcers or those taking aspirin or clopidogrel. Half of the study participants received rivaroxaban 10 mg/day for 35 days as part of post-discharge advice, while the remaining half received no anticoagulation. The primary efficacy outcome was the occurrence of symptomatic VTE and VTE related-death, while incidence of any major bleeding was considered as the primary safety outcome. All patients had received standard in-hospital parenteral thromboprophylaxis and 52% needed intensive care. Around 62% patients had an IMPROVE VTE score of 2-3 and raised D-dimers, while 38% had IMPROVE VTE scores of ≥4.

Five (3.14%) cases of VTE or VTE-related death were noted in the rivaroxaban group at day 35 compared to 15 (9.43%) such events in the group of patients who received no anticoagulation treatment (relative risk 0.33) as reported in The Lancet with a relative risk of 0.33. This difference was mainly attributed to fewer episodes of pulmonary embolism (PE) detected by CT pulmonary angiogram in the rivaroxaban group (one symptomatic and one asymptomatic PE) vis-à-vis control group, which had four asymptomatic, three symptomatic and three fatal episodes of PE.

Another difference observed between the two groups was in the severity of VTE events. The study group not only had lower incidence of VTE events, they were also less severe i.e., more asymptomatic events were recorded in the group on extended anticoagulation compared to the control group. These results were consistent across all subgroups of patients hospitalized with COVID-19.

One percent of patients reported allergic reactions with the oral anticoagulant.

These findings demonstrate the beneficial effects of continuing anticoagulation treatment for high risk COVID-19 patients. Extending thromboprophylaxis treatment after discharge with low-dose rivaroxaban for at least one month improved clinical outcomes by reducing risk of major and fatal VTE without any detrimental effect on the risk of major bleeding compared to those who did not receive any anticoagulation after discharge. COVID-19 causes a hypercoagulable state, which can lead to thromboembolic complications, particularly in the at-risk patients.

Hence, all high-risk hospitalized patients should routinely be prescribed extended prophylactic-dose rivaroxaban at hospital discharge. According to the study authors, this is the first randomized trial to show benefit of extended post-discharge thromboprophylaxis in COVID-19 patients. They write, “These results provide high-quality evidence and will inform clinical practice guidelines about the role of extended thromboprophylaxis in hospitalised patients with COVID-19.”

Reference

1. Ramacciotti E, et al. Rivaroxaban versus no anticoagulation for post-discharge thromboprophylaxis after hospitalisation for COVID-19 (MICHELLE): an open-label, multicentre, randomised, controlled trial. Lancet. 2021 Dec 15;S0140-6736(21)02392-8. doi: 10.1016/S0140-6736(21)02392-8.