Hospitalized COVID-19 patients at high risk for venous thromboembolism (VTE) saw improved clinical outcomes and a lower VTE risk without an increased risk for bleeding with thromboprophylaxis using rivaroxaban post-discharge compared to no anticoagulation, according to trial results released Sunday.
Eduardo Ramacciotti, MD, of the Valley Research Institute, Fresno, California, reported results from the MICHELLE (Medically Ill Hospitalized Patients for COVID-19 THrombosis Extended ProphyLaxis With Rivaroxaban ThErapy) Trial on Sunday at the virtual European Society of Cardiology Congress 2021.
COVID-19 is associated with a pro-thrombotic state. The mechanism of action may be a result of the direct effect the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has, secondary to the associated cytokine storm and endothelial damage or a combination of both mechanisms. For patients hospitalized with COVID-19, there is a role for thromboprophylaxis; however, the role of extended thromboprophylaxis remains unclear.
The MICHELLE Trial was a prospective, randomized, open-label, controlled, multicenter trial of 320 hospitalized COVID-19 patients treated with standard-dose thromboprophylaxis who were at high risk for VTE (IMPROVE score >3 or 2-3 with a D-dimer >500 ng/mL). Upon discharge, the patients were randomized to receive either 10 mg of rivaroxaban daily for 35 days or no anticoagulation. Afterward, patients underwent Doppler ultrasonography and pulmonary angiogram computed tomography. Patients were then contacted at 75 days via phone.
The primary outcome was a composite of symptomatic VTE, VTE-related death, VTE detected at bilateral lower limbs venous duplex scan and computed tomography pulmonary angiography, myocardial infarction, non-hemorrhagic stroke, major adverse limb events (MALE) or cardiovascular death at day 35.
The primary composite outcome occurred less frequently in patients who received anticoagulation (3.14% vs. 9.43%; relative risk reduction, 67%; relative risk [RR], 0.33; 95% confidence interval [CI], 0.13, 0.90; p=0.03 for superiority; number needed to treat = 16).
Turning to secondary efficacy outcomes, symptomatic and fatal VTE (0.63% vs. 5.03%; RR, 0.13; 95% CI, 0.02, 0.99), and the composite of symptomatic VTE, myocardial infarction, stroke and cardiovascular death (0.63% vs. 5.66%; RR, 0.11; 95% CI, 0.01, 0.87) occurred less frequently in patients who received rivaroxaban. The composite of symptomatic VTE and all-cause mortality also occurred less frequently in patients given rivaroxaban; however, this difference was not statistically significant (2.52% vs. 5.66%; RR, 0.44; 95% CI, 0.14, 1.41).
The principal safety outcome of major bleeding did not occur in any patients in either the treatment or control group.