Direct oral anticoagulants versus vitamin-K antagonists in patients with single or double-positive antiphospholipid syndrome: a systematic review and meta-analysis.

Background: Antiphospholipid syndrome (APS) is a heterogeneous disease where the presence of antiphospholipid antibodies (aPL) results in blood clot formation. Compared to those with a triple-positive antibody profile, the optimal anticoagulant strategy in patients with a single or double-positive APS is still debated due to their different risks of recurrent thrombosis.

Objective: This systematic review and meta-analysis aims to investigate the efficacy and safety of Direct Oral Anticoagulants (DOACs) compared to Vitamin-K Antagonists (VKAs) for treating single or double-positive APS.

Methods: Medline and EMBASE databases were searched until September 2024 for randomized clinical trials (RCTs) and observational studies that included patients with APS positive to a single or double aPL test. Pooled Risk Ratios (RRs) and 95% CIs were estimated by a random-effects model.

Results: Three RCTs and seven observational studies were included in the efficacy analysis, totaling 439 patients treated with DOACs and 481 with VKAs. No difference in the risk of thrombosis recurrences was observed between the two treatments (RR 0.78, 95% CI 0.36-1.69), despite an opposite trend in RCTs (RR 2.54, 95% CI 0.61-10.59) compared with the observational studies (RR 0.60, 95% CI 0.25-1.39). Two RCTs and six observational studies reported data on bleeding, totaling 287 patients in the DOACs and 367 in the VKAs group. No difference in the risk of major bleeding/clinically relevant nonmajor bleeding (CRNMB) between treatments was detected (RR 0.78, 95% CI 0.30-2.05).

Conclusions: DOACs could be an effective and safe alternative to VKAs for managing single or double-positive APS.