Rivaroxaban versus no anticoagulation for post-discharge thromboprophylaxis after hospitalisation for COVID-19 (MICHELLE): an open-label, multicentre, randomised, controlled trial

Abstract

Background Patients hospitalised with COVID-19 are at risk for thrombotic events after discharge; the role of extended thromboprophylaxis in this population is unknown. Methods In this open-label, multicentre, randomised trial conducted at 14 centres in Brazil, patients hospitalised with COVID-19 at increased risk for venous thromboembolism (International Medical Prevention Registry on Venous Thromboembolism [IMPROVE] venous thromboembolism [VTE] score of ≥4 or 2–3 with a D-dimer >500 ng/mL) were randomly assigned (1:1) to receive, at hospital discharge, rivaroxaban 10 mg/day or no anticoagulation for 35 days. The primary efficacy outcome in an intention-to-treat analysis was a composite of symptomatic or fatal venous thromboembolism, asymptomatic venous thromboembolism on bilateral lower-limb venous ultrasound and CT pulmonary angiogram, symptomatic arterial thromboembolism, and cardiovascular death at day 35. Adjudication was blinded. The primary safety outcome was major bleeding. The primary and safety analyses were carried out in the intention-to-treat population. This trial is registered at ClinicalTrials.gov , NCT04662684 . 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. Interpretation In patients at high risk discharged after hospitalisation due to COVID-19, thromboprophylaxis with rivaroxaban 10 mg/day for 35 days improved clinical outcomes compared with no extended thromboprophylaxis. Funding Bayer.

Deaths related to pulmonary embolism and cardiovascular events before and during the 2020 COVID-19 pandemic: An epidemiological analysis of data from an Italian high-risk area

“…The COVID-19 pandemic may have led to a reduction in the use of imaging tests for diagnostic workup [8] , [10] . Furthermore, a broader and more aggressive use of pharmacological preventative measures for venous thromboembolism may have partly reduced this risk, as recently shown by trials conducted in the hospital and ambulatory setting [11] , [12] . One nationwide French study illustrated that the number of pulmonary embolism-related hospitalizations and in-hospital fatality increased in 2020, particularly during the COVID-19 waves [13] .…”

Extensive Pulmonary Embolism Following Mild COVID-19 Pneumonia

“…Coagulopathy in COVID-19 has a wide spectrum of clinical presentations with variable severity ranging from asymptomatic to organ dysfunction and death. From the early period of COVID-19, it has been recognized that venous thromboembolic diseases, including deep venous thrombosis and pulmonary embolism, are very prevalent among acutely ill patients [5]. Further, the coagulopathy complications may include arterial events resulting in a stroke, myocardial infarction, and limb ischemia [6].…”

Coagulopathy and Fibrinolytic Pathophysiology in COVID-19 and SARS-CoV-2 Vaccination

“…Patients with COVID-19 are often treated with heparin during hospitalization to prevent thrombosis. However, the hypercoagulable state often persists after discharge [ 138 , 139 , 140 ], and some reports have suggested that transition to a direct oral anticoagulant (DOAC) at discharge may be useful [ 141 ].…”