Efficacy and safety of direct oral anticoagulants compared with warfarin in antiphospholipid syndrome. Results of a multicenter retrospective cohort study

Background: Direct oral anticoagulants (DOACs) have become firstline treatment for many thrombotic conditions, but their use in antiphospholipid syndrome (APS) patients remains controversial. Objectives: This multicenter, retrospective cohort study conducted at Emory and McMaster University Medical Centers aimed to explore pattern of DOAC use among APS patients and compare the efficacy and safety of DOACs vs warfarin. Methods: We included APS patients aged ≥18 years who experienced acute thrombosis between 2012 and 2018 and initiated DOACs or warfarin. Clinical endpoints were recurrent thrombosis, clinically relevant bleeding, and a composite of thrombosis and bleeding (net clinical benefit). Cox proportional hazards models estimated hazard ratios (HRs) for the clinical endpoints and defined DOAC or warfarin exposure as time-varying to account for anticoagulant switching. Results: A total of 152 patients were identified: 77 initiated treatment with warfarin and 75 with DOACs. Sixty patients switched anticoagulation therapy at least once. Twenty-four patients had triple-positive antiphospholipid antibodies anticoagulation class (DOAC vs warfarin) did not influence risk of recurrent thrombosis (HR, 0.91; 95% CI, 0.46-1.79) or net clinical benefit (HR, 0.81; 95% CI, 0.46-1.43). Conversely, DOACs were associated with 57% reduction in risk of clinically relevant bleeding (HR, 0.43; 95% CI, 0.20-0.95). The risk of recurrent venous or arterial thrombosis was comparable between DOAC and warfarin cohorts. Conclusion: This study demonstrated comparable efficacy and improved safety of DOACs over warfarin in a predominantly lower-risk APS population. Caution is advised, particularly in APS patients with triple-positive antiphospholipid antibodies or history of arterial thrombosis.