What is the preferred anticoagulant, warfarin or direct acting anticoagulants (DAA) such as rivaroxaban (Xarelto) or apixaban (Eliquis), for patients with antiphospholipid antibody syndrome?

Warfarin is the Preferred Anticoagulant for Antiphospholipid Antibody Syndrome, Not Direct Acting Anticoagulants

Warfarin is strongly recommended over direct acting anticoagulants (DAOCs) for patients with antiphospholipid antibody syndrome (APS), as DOACs are associated with excess thrombotic events compared to warfarin, particularly in high-risk patients. 1

Diagnosis and Classification of APS

• APS is characterized by persistent (repeat testing 12 weeks apart) presence of lupus anticoagulant, anti-cardiolipin, or anti-β2 glycoprotein-I antibodies plus clinical evidence of vascular thrombosis or pregnancy morbidity 1, 2
• Triple-positive APS (positive for all three antibodies) represents the highest risk category for thrombotic events 2
• Testing for APS should be considered in patients with:
  • Prior venous thromboembolism 1
  • Second trimester abortion 1
  • Rheumatologic disorders 1
  • Cryptogenic stroke with history of thrombosis 1

Anticoagulation Recommendations

First-Line Therapy: Warfarin

• Warfarin with target INR 2.0-3.0 is the recommended first-line therapy for confirmed APS 1, 2
• For patients with ischemic stroke or TIA who meet APS criteria, warfarin anticoagulation is reasonable to reduce recurrent stroke/TIA risk 1
• Target INR 2.0-3.0 provides optimal balance between thrombosis prevention and bleeding risk 1, 2
• High-intensity warfarin (INR >3) is not recommended as it increases bleeding risk without providing additional thrombosis protection 1, 3

DOACs: Not Recommended

• Rivaroxaban is specifically contraindicated in APS, especially in triple-positive patients 1, 4
• In an open-label RCT of high-risk triple-positive APS patients, rivaroxaban was associated with 19% event rate compared to 3% with warfarin 4
• Other DOACs (apixaban, dabigatran) should also be avoided until further evidence is available 2, 5
• Even in single or double antibody-positive APS, DOACs showed nearly three times higher thromboembolism recurrence rates compared to warfarin (15.4% vs 5.3%) 6

Special Situations

• For patients with isolated antiphospholipid antibody who do not fulfill complete APS criteria, antiplatelet therapy alone (aspirin) is recommended 1, 2
• When testing for APS, antibody testing should be deferred or repeated at least 4-6 weeks after acute thrombosis as protein levels may be altered during the acute phase 1

Monitoring and Follow-up

• Regular INR monitoring is essential for patients on warfarin therapy 2
• The highest risk of thrombosis recurrence occurs during the first six months after warfarin discontinuation 3
• Triple-positive APS patients require particularly careful monitoring and strict adherence to warfarin therapy 2, 4

Knowledge Gaps and Ongoing Research

• The ASTRO-APS trial is evaluating whether increased thrombosis risk with DOACs is a class effect or specific to rivaroxaban 1
• There is ongoing research to determine if DOACs might be appropriate for specific APS subgroups (e.g., venous-only thrombosis with single antibody positivity) 5
• The role of dual antiplatelet therapy in APS requires further investigation 1