The efficacy and safety of direct oral anticoagulants (DOACs) for patients with thrombotic antiphospholipid syndrome (APS) remain controversial.
We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) that compared DOACs with vitamin-K antagonists (VKAs).
We searched PubMed, EMBASE, and Cochrane Central Register of Controlled Trials through April 9, 2022. The two main efficacy outcomes were a composite of arterial thrombotic events, and venous thromboembolic events (VTE). The main safety outcome was major bleeding. Random effects models with inverse variance were used.
Our search retrieved 253 studies. Four open-label RCTs involving 472 patients were included (mean control-arm time-in-therapeutic-range: 60%). All had proper random sequence generation and adequate allocation concealment. Overall, use of DOACs compared with VKAs was associated with increased odds of subsequent arterial thrombotic events (OR 5.43, 95% confidence interval [CI] 1.87-15.75, p < 0.001, I2 = 0%), especially stroke, and composite of arterial thrombotic events or VTE (OR 4.46, 95% CI 1.12-17.84, p = 0.03, I2 = 0%). The odds of subsequent VTE (OR 1.20, 95% CI 0.31-4.55, p = 0.79, I2 = 0%), or major bleeding (OR 1.02, 95% CI 0.42-2.47, p = 0.97, I2 = 0%) were not significantly different between the two groups. Most findings were consistent within subgroups.
Patients with thrombotic APS randomized to DOACs compared to VKAs appear to have increased risk for arterial thrombosis. No significant differences were observed between patients randomized to DOACs vs VKAs in the risk of subsequent VTE or major bleeding.