In patients hospitalized with COVID-19 at increased risk for thrombotic events, thromboprophylaxis with rivaroxaban following discharge was found to be associated with improved clinical outcomes compared with no postdischarge anticoagulation therapy, according to results of a study published in Lancet.
Researchers recruited patients from 14 centers in Brazil for this open label, randomized trial. Patients were hospitalized with COVID-19 and at increased risk for venous thromboembolism (VTE). Patients were considered to be at increased risk for VTE if they had an international medical prevention registry on venous thromboembolism (IMPROVE) predictive score of greater than or equal to 4 or between 2 and 3 with a D-dimer concentration of greater than 500 ng/mL. Patients were randomly assigned in a 1:1 fashion to receive either rivaroxaban 10 mg daily or no anticoagulation for 35 days following hospital discharge (ClinicalTrials.gov, NCT04662684). In an intention-to-treat analysis, the primary efficacy outcome was a composite of symptomatic or fatal VTE, asymptomatic VTE on ultrasonography of the bilateral lower extremities and CT pulmonary angiography, symptomatic arterial thromboembolism, and cardiovascular death. Major bleeding was the primary safety outcome.
Overall, a total of 320 patients met eligibility criteria and were included in the final analysis. Of these patients, 160 received rivaroxaban and 160 received no anticoagulation therapy. Of note, 1 patient from each group was lost to follow-up. All patients received thromboprophylaxis with a standard dose of heparin during hospitalization. An IMPROVE predictive score of 2 to 3 with an increased D-dimer concentration was observed in 197 patients. In addition, an IMPROVE predictive score of 4 or more was observed in 121 patients, and 165 were hospitalized in the intensive care unit.
The primary outcome occurred in 5 (3%) and 15 (9%) patients in the rivaroxaban and no anticoagulation therapy groups, respectively (relative risk, 0.33; 95% CI, 0.12-0.90; P = .0293). Although no major bleeding events were observed among patients in either group, an allergic reaction was reported by 2 patients who received rivaroxaban.
Study limitations included its small sample size, open-label design, and the lack of a placebo. In addition, the researchers were unable to differentiate between pulmonary embolism and immunomediated primary pulmonary embolism or arterial thrombosis.
According to researchers, “in the era of the COVID-19 pandemic, in which most medical decisions regarding anticoagulation strategies have been made based on low-quality evidence, our study provides high-quality data to help clinicians in the decision making process when managing and treating patients with COVID-19.”
Disclosure: Some authors declared affiliations with biotech, pharmaceutical, and/or device companies, and this research was funded by Bayer. Please see the original reference for a full list of disclosures.
Ramacciotti E, Barile Agati L, Calderaro D, et al. Rivaroxaban versus no anticoagulation for post-discharge thromboprophylaxis after hospitalisation for COVID-19 (MICHELLE): an open-label, multicentre, randomised, controlled trial. Lancet. Published online December 15, 2021. doi:10.1016/S0140-6736(21)02392-8