Risk of post-thrombotic syndrome following direct oral anticoagulant intake: a systematic review and meta-analysis

Abstract

To perform a systematic review and meta-analysis of data devoted to the risk of post-thrombotic syndrome (PTS) following direct oral anticoagulant (DOAC) intake. A systematic review and meta-analysis of trials available in the PubMed database were performed in March 2021. Analysis included the reports with known Villalta score for PTS in patients receiving DOACs or alternative anticoagulation. We analyzed the incidence and risk of any form of PTS. We found 10 comparative studies comprising 3161 patients. Incidence of PTS under DOAC therapy was 30.8% (95% confidence interval (CI) 22.2-39.3%), severe PTS - 2.2% (95% CI 1.0-3.4%). DOACs were associated with significantly less risk of any form of PTS (odds ratio (OR) 0.57; 95% CI 0.48-0.68; p<0.001) and severe PTS (OR 0.56; 95% CI 0.36-0.87; p=0.010) compared to vitamin K antagonists. Among various DOACs, specified data were available only for rivaroxaban (OR 0.54, 95% CI 0.42-0.71, p<0.001 for any PTS; OR 0.49, 95% CI 0.27-0.89, p=0.019 for severe PTS). The use of flavonoids in adjunction to rivaroxaban was associated with additional risk reduction for PTS (OR 0.14; 95% CI 0.06-0.31; p<0.001). Moderate quality evidence suggests that DOACs are associated with significant less risk of any PTS and severe PTS compared to VKA in patients with deep vein thrombosis. Among all DOACs, only rivaroxaban has clear data confirming PTS risk reduction. The use of flavonoids in adjunction to rivaroxaban can further improve treatment outcomes.