Direct oral anticoagulants versus Vitamin K antagonists in antiphospholipid syndrome: A systematic review and meta-analysis.

BACKGROUND

Randomized controlled trials (RCTs) comparing the efficacy and safety of direct oral anticoagulants (DOACs) versus Vitamin K antagonists (VKAs) in patients with thrombotic antiphospholipid syndrome (APS) have yielded inconsistent results, partly due to the inherent challenges of conducting RCTs in populations with rare medical conditions. We conducted a systematic review and meta-analysis to evaluate the comparative effects of DOACs versus VKAs in thrombotic APS.

METHODS

RCTs and observational studies comparing DOACs versus VKAs in patients with thrombotic APS were included. The primary endpoint was a composite of arterial (ATE) and venous thrombotic events (VTE). Incidence rate ratios (IRRs) and associated 95 % confidence intervals (CI) were used to account for different follow-up durations. GRADE was used for rating the certainty of evidence.

FINDINGS

Twelve studies, four randomized and eight observational, encompassing a total of 1307 APS patients were included. The use of DOACs was associated with an increase in the primary endpoint (IRR 2.33; 95 % CI 1.18-4.58; GRADE=moderate) driven by increased ATE (IRR 2.70; 95 % CI 1.42-5.13; GRADE=low), compared with the use of VKA. VTE (IRR 0.98; 95 % CI 0.59-1.64; GRADE=low), major (IRR 0.83; 95 % CI 0.48-1.43; GRADE=low) and non-major (IRR 1.32; 95 % CI 0.81-2.14; GRADE=very low) bleeding did not differ significantly between groups. Compared with VKAs, DOACs were associated with an increase in myocardial infarction (IRR 4.71; 95 % CI 1.00-22.21; GRADE=very low) and stroke (IRR 7.48; 95 % CI 1.27-44.13; GRADE=very low). The increased risk of arterial thrombotic events with DOACs was consistently observed in a dedicated analysis of RCTs and was mitigated by the concomitant use of single antiplatelet therapy.

INTERPRETATION

In patients with thrombotic APS, the use of DOACs is associated with increased thrombotic events compared with VKAs, mainly driven by arterial thrombotic events. A single antiplatelet therapy combined with DOACs maight offer a promising alternative to VKAs, warranting further dedicated investigations.

PRIMARY FUNDING SOURCE

The study was not funded.

PROTOCOL REGISTRATION

This study is registered in PROSPERO (CRD42024582033).