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DOACs vs. VKAs in Thrombotic Antiphospholipid Syndrome
Quick Takes
- Patients with thrombotic antiphospholipid syndrome (APS) have fewer arterial thrombotic events when treated with VKAs versus DOACs.
- Patients with thrombotic APS had similar rates of VTE and major bleeding when treated with VKAs versus DOACs.
- The benefits of VKAs over DOACs were similar across important subgroups of patients with thrombotic APS, including type of thrombosis and number of positive antibodies.
Study Questions:
What is the efficacy and safety of direct oral anticoagulants (DOACs) for patients with thrombotic antiphospholipid syndrome (APS)?
Methods:
The authors performed a systematic review and meta-analysis of randomized controlled trials (RCTs) that compare DOACs with vitamin K antagonists (VKAs) published through April 9, 2022. The two main efficacy outcomes were a composite of arterial thrombotic events and venous thromboembolic events (VTEs). The main safety outcome was major bleeding.
Results:
Four open-label randomized controlled trials (RCTs) involving 472 patients were included in the meta-analysis. The mean time in therapeutic range for the VKA-treated arms was 60%. Overall, use of DOACs compared to VKAs was associated with increased odds of subsequent arterial events (10.3% vs. 1.3%, odds ratio [OR], 5.43; 95% confidence interval [CI], 1.87-15.75), most significantly for stroke (8.6% vs. 0%, OR, 10.74; 95% CI, 2.29-50.38). Similarly, the composite of arterial or venous thrombotic events (11.5% vs. 2.5%, OR, 4.46; 95% CI, 1.12-17.84) was higher for DOAC- versus VKA-treated groups. The odds of subsequent VTE (1.7% vs. 1.3%, OR, 1.20; 95% CI, 0.31-4.55) and major bleeding (4.3% vs. 4.2%, OR, 1.02; 95% CI, 0.42-2.47) were not significant between the two groups. There was no difference in the main outcome between those with “triple positive” and other forms of APS as well as for patients with prior arterial versus venous thrombotic events.
Conclusions:
The authors concluded that patients with thrombotic APS randomized to DOACs, as compared to VKAs, appear to have increased risk for arterial thrombotic events.
Perspective:
Patients with APS are at elevated risk for both arterial and venous thrombotic events. While DOACs have become first-line treatment for most patients with VTE, RCTs among patients with APS have shown better outcomes with VKA than DOAC treatment. However, these trials were relatively small and enrolled populations with different levels of thrombotic events. This meta-analysis highlights several important findings. First, the rate of arterial events was higher than VTE, especially among the DOAC-treated arms. Second, patients had fewer arterial and composite arterial plus venous thrombotic events when treated with VKAs than DOACs. Third, the benefits of DOACs over VKAs were consistent across most subgroups, including those with “triple positive” versus single or double positive APS, patients with arterial versus venous thrombotic index events, and male versus female. Clinically, patients should be aware of these discrepancies when deciding between VKAs and DOACs for prevention of future thrombotic events. This meta-analysis supports VKAs as first-line therapy for most patients with thrombotic APS.
Clinical Topics: Anticoagulation Management, Prevention, Pulmonary Hypertension and Venous Thromboembolism, Vascular Medicine, Anticoagulation Management and Venothromboembolism
Keywords: AHA22, AHA Annual Scientific Sessions, Antibodies, Anticoagulants, Antiphospholipid Syndrome, Hemorrhage, Risk, Secondary Prevention, Stroke, Thrombosis, Vascular Diseases, Venous Thromboembolism, Vitamin K
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