Background/Purpose:

Long-term anticoagulation with vitamin K antagonists (VKAs) is the standard of care in thrombotic antiphospholipid syndrome (APS) but requires frequent monitoring and dose adjustment. Rivaroxaban, an orally active direct factor Xa inhibitor, provides more consistent anticoagulation but its use in APS is controversial.

Methods:

This is a phase 3 non-inferiority open-label RCT. We randomly (1:1) assigned 190 patients with thrombotic APS (arterial or venous) receiving warfarin to receive either rivaroxaban (at a daily dose of 20 mg) or dose-adjusted acenocumarol (standard of care, normalized ratio (INR) 2-3 or 3.1 to 4.1 in those with recurrent thrombotic episodes). The per-protocol analysis was designed to determine the rivaroxaban noninferiority to warfarin for the primary endpoint of recurrent thrombosis. Secondary efficacy outcomes include time to thrombosis, type of recurrent events (arterial or venous), and overall causes of death. The primary safety outcome was major bleeding.

Results:

In the primary analysis, thrombotic events occurred in 11 patients in the rivaroxaban group (11.6%; 4.59 patients-year) and in 6 patients in the VKAs group (6.3%; 2.26 patients-year) (hazard ratio, 1.93; 95% CI, 0.69 to 5.39; p=0.210). In the intention-to treat analysis, thrombotic events occurred in 12 patients in the rivaroxaban group (12.6%; 4.68 patients-year) and in 6 patients in the VKAs group (6.3%; 2.22 patients-year) (hazard ratio, 2.13; 95% CI, 0.77 to 5.88; p=0.144). in the per-protocol population and in the intention-to-treat population, patients in the rivaroxaban group had a higher rate of stroke (9 events (3.75 patient-year) and 10 events (3.90 patient-year), respectively, than those in the VKAs group (0 events) (hazard ratio in the rivaroxaban group, 16.16; 95% CI, 0.84 to 309.43; p=0.065, in the PP study and 20.04; 95% CI, 1.04 to 386.58; p=0.047 in the ITT study). Major and nonmajor clinically relevant bleeding occurred similarly in both groups (31.6% in the rivaroxaban and 26.3% in the VKAs), but with less intracranial hemorrhage and critically significant bleeding in the rivaroxaban group

Conclusion:

In patients with APS, rivaroxaban could not demonstrate its noninferiority to VKAs for the prevention of recurrent thrombosis, and stroke occurred more frequently in the rivaroxaban group. There were no significant between-group difference in the risk of major bleeding, although critical bleeding occurred less frequently in the rivaroxaban (ClinicalTrials.gov number: 02926170)

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/rivaroxaban-versus-warfarin-as-secondary-thromboprophylaxis-in-patients-with-antiphospholipid-syndrome-a-randomized-multicenter-open-label-clinical-trial/