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

Abstract

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

Objectives: This systematic review and meta‑analysis aimed to investigate the efficacy and safety of direct oral anticoagulants (DOACs) and vitamin K antagonists (VKAs) for treating single- or double‑positive APS.

Patients and methods: The 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 with a random‑effects model.

Results: Three RCTs and 7 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 recurrence was observed between the 2 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) as compared with the observational studies (RR, 0.6; 95% CI, 0.25-1.39). Two RCTs and 6 observational studies reported data on bleeding, totaling 287 patients in the DOAC and 367 in the VKA group. No difference in the risk of major bleeding / clinically relevant nonmajor bleeding between treatments was detected (RR, 0.78; 95% CI, 0.3-2.05).

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