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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; I2 = 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.

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