Efficacy and Safety of DOACs for the Treatment of Superficial Vein Thrombosis: A Systematic Review and Meta-Analysis

Abstract Direct oral anticoagulants (DOACs) are increasingly used for superficial vein thrombosis (SVT), yet evidence remains limited. This systematic review and meta-analysis synthesizes all available data on the efficacy and safety of DOACs in SVT. A systematic search identified randomized and observational studies enrolling adults with acute SVT treated with DOACs. Primary efficacy outcomes were venous thromboembolism (VTE: deep vein thrombosis or pulmonary embolism) and SVT recurrence/extension. Safety outcomes included major and clinically relevant non-major bleeding (CRNMB). Six studies (n = 2,040; 602 DOAC-treated patients) met the inclusion criteria. Compared with fondaparinux, DOACs showed comparable short-term efficacy for VTE prevention (pooled risk ratio [RR] 0.93, 95% CI 0.44–1.99) and similar rates of SVT recurrence (RR 1.30, 95% CI 0.65–2.62). Versus placebo, rivaroxaban reduced recurrence by approximately 80% (RR 0.20, 95% CI 0.03–1.35). In the pooled safety analysis including four studies, DOACs were associated with a 65% relative risk reduction in major or CRNMB compared with fondaparinux or low-molecular-weight heparin (RR 0.35, 95% CI 0.15–0.83; I 2 = 0%). In the TROLL registry (n = 229; 74% DOAC), no major bleeding occurred among DOAC users, while 5-year cumulative VTE and SVT recurrence rates were each 15.9%. Certainty of evidence was moderate for efficacy and high for safety. DOACs demonstrate efficacy comparable to fondaparinux and an excellent safety profile in SVT, supporting their use as a practical oral alternative. Long-term data indicate persistent thrombotic risk, suggesting potential benefit of extended low-dose prophylaxis in selected high-risk patients.