After COVID-19 hospitalization extended thromboprophylaxis with DOAC improves outcomes
Rivaroxaban versus no anticoagulation for post-discharge thromboprophylaxis after hospitalization for COVID-19 (MICHELLE): an open-label, multicentre, randomised, controlled trial
Introduction and methods
Background
Use of prophylactic parenteral anticoagulants during hospitalization for COVID-19 is recommended, with consensus on the role of in-hospital heparin as primary thromboprophylaxis [1-3]. It is unclear what to do beyond the hospital stay and whether extended venous thromboembolism prophylaxis after hospitalization due to COVID-19 lowers venous thromboembolism, arterial thromboembolism or all-cause death [4-6].
This study investigated whether prophylaxis with rivaroxaban 10 mg/day for 35 days after discharge improved clinical outcomes in patients hospitalized with COVID-19.
Study design
The MICHELLE trial was an open-label, multicenter, randomized, controlled trial with blinded adjudication of outcomes in patient discharged after hospitalization for COVID-19, conducted in Brazil. Patients had to have an increased risk for venous thromboembolism (an elevated modified IMPROVE VTE score of 2-3 with a D-dimer >500 ng/mL or a score of ≥4. 320 Patients were randomized in a 1:1 ratio to rivaroxaban 10 mg/day or no anticoagulation for 35 days. At day 35, bilateral lower limb venous Doppler ultrasound and CT pulmonary angiograms were performed. Median hospitalization time was 8 days (IQR 6-12) and 52% of patients were in the ICU.
Primary outcomes
Primary efficacy outcome was a composite of symptomatic or fatal venous thromboembolism, asymptomatic venous thromboembolism detected by bilateral lower limb venous Doppler ultrasound and CT pulmonary angiogram, symptomatic arterial thromboembolism (MI, non-hemorrhagic stroke and major adverse limb event) and CV death at day 35.
Primary safety outcome was major bleeding, defined according to the ISTH criteria.
Main results
Primary outcomes
- A primary efficacy outcome event occurred in 3.14% of patients in the rivaroxaban group and 9.43% in the control group (RR 0.33, 95%CI: 0.13-0.90, P=0.0293).
- This primary outcome was mainly driven by pulmonary embolism in the control group.
- There were no ISTH-defined major bleeding events in either group.
- Results were consistent across prespecified subgroups with no signs of heterogeneity.
Secondary outcomes
- Symptomatic and fatal venous thromboembolism occurred in 1 patient in the rivaroxaban group and in 8 in the control group (RR 0.13, 95%CI:0.02-0.99, P=0.0487).
- Symptomatic venous thromboembolism and all-cause mortality occurred in 4 patients in the rivaroxaban group and 9 in the control group (RR 0.44, 95%CI:0.14-1.41, P=0.1696).
- The composite of symptomatic venous thromboembolism, MI, stroke or CV death occurred in 1 patient in the rivaroxaban group and in 9 patients in the control group (RR 0.11, 95%CI:0.01-0.98, P=0.0360).
- Clinically relevant non-major bleeding occurred in 2 patients in the rivaroxaban group and in 2 in the control group. The combination of major, clinically relevant non-major, and other bleeding occurred in 4 patients receiving rivaroxaban and in 3 allocated to no anticoagulation.
Conclusion
This open-label, multicenter, randomized, controlled trial of patients who were hospitalized with confirmed COVID-19 showed that extended post-discharge thromboprophylaxis with rivaroxaban for 35 days reduced the risk of the composite of venous or arterial thromboembolism or CV death compared to no anticoagulation. There was no increase in major bleeding in the rivaroxaban group.
The authors state that use of extended prophylaxis with rivaroxaban can be an attractive strategy in patients with creatinine clearance >30 mL/min who were hospitalized with COVID-19 and had an IMPROVE VTE score 2-3 plus increased D-dimer levels or an score of ≥4.
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