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Abstract
A meta-analysis of the four relevant randomized clinical trials evaluating direct oral anticoagulants (DOACs) versus warfarin in thrombotic antiphospholipid syndrome (APS) showed a significant increase in arterial thrombotic events, specifically stroke.1 No significant increase in venous thromboembolisms (VTE) or major bleeding was observed in patients receiving DOACs compared to those receiving vitamin K antagonists. The findings of this study do not support the routine use of existing DOAC regimens in patients with thrombotic APS.
The conclusions of this meta-analysis are further supported by data reported two years after the closure of Trial of Rivaroxaban in AntiPhospholipid Syndrome (TRAPS).2 Despite strong recommendations to stop rivaroxaban and take warfarin, six patients decided to continue taking DOACs. During the two-year follow-up period, eight events (i.e. thrombosis, major bleeding, and vascular death) were reported.
Two thrombotic events (one deep wein thromosis on dabigatran 150 mg bd and one ischemic stroke on rivaroxaban 20 mg od) occurred in the six patients who remained on DOACs (33.3%) and six (i.e. three thrombotic, two hemorrhagic and one vascular death) occurred in the 109 patients on warfarin (5.5%).2
On Cox regression, the risk of cumulative events was significantly higher in the DOACs group (HR 6.9; 95% CI 1.4–34.5, p=0.018).2 Reasons for DOACs failure may include poor adherence, suboptimal drug concentration with higher levels might be needed for arterial circulation with the disadvantage of bleeding risk.
Mechanism of action could be involved; warfarin inhibits the intrinsic pathway, which is important for thrombin generation, and reduces prothrombin level, providing less antigen to anti-phosphatidylserine/prothrombin antibodies always present in triple-positive patients.
Uncertainties remain about whether all thrombotic APS patients should avoid DOACs or only those at high risk of recurrence (i.e. triple positive) and only those with arterial thrombosis.
References
Khairani CD, Bejjani A, Piazza G, et al. Direct oral anticoagulants vs vitamin K antagonists in patients with antiphospholipid syndromes: Meta-analysis of randomized trials. J Am Coll Cardiol. 2023;81(1):16–30. doi: 10.1016/j.jacc.2022.10.008.
Pengo V, Hoxha A, Andreoli L, et al. Trial of rivaroxaban in antiphospholipid syndrome (TRAPS): Two-year outcomes after the study closure. J Thromb Haemost. 2021;19(2):531–35. doi: 10.1111/jth.15158.
Learning Objectives At the end of this presentation participants will be able to:
Explain why DOACs should not be used in patients with thrombotic APS
Discuss why more studies are needed to assess whether this assumption is valid for high-risk patients (i.e. triple positive) only
Discuss why more studies are needed to assess whether DOACs could be used in low risk (double or single positive) patients with VTE
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