Antiphospholipid Syndrome: Management & Future Directions

Dr. Ortel began with the recent European League Against Rheumatism (EULAR) recommendations for the management of APS in adults.² EULAR emphasizes that high-quality evidence is limited in APS. Nevertheless, the EULAR recommendations state that anticoagulant therapy is the treatment of choice for APS patients with new venous thromboembolism (VTE). Treatment should be initiated with either unfractionated heparin or low molecular weight heparin. When treating a first VTE, EULAR suggests that direct oral anticoagulants be considered in patients not able to achieve a target international normalized ratio (INR) despite good adherence to vitamin K antagonist or those with contraindications to vitamin K antagonist, such as allergy.

TRAPS Study
The Trial on Rivaroxaban in AntiPhospholipid Syndrome (TRAPS) study, a randomized, controlled trial that compared the ability of rivaroxaban and warfarin to prevent recurrent thrombosis in patients with APS and a prior thrombotic event, enrolled high-risk patients who were triple positive for lupus anticoagulant, anti-cardiolipin and anti-β₂GPI, and these patients were randomized to receive either rivaroxaban 20 mg/day or warfarin, with a target INR of two to three.³ The study closed after 120 patients were enrolled because it showed an increased rate of events with rivaroxaban compared to warfarin. A second prospective, randomized clinical trial comparing rivaroxaban to warfarin obtained similar results.⁴

A recent Cochrane Review addressed antiplatelet and anticoagulant agents for secondary prevention of stroke and other thromboembolic events in people with APS.⁵ The authors identified eight studies including 811 participants that compared different antiplatelet or anticoagulant agents. They concluded that non-vitamin K antagonist oral anticoagulants, such as rivaroxaban, compared with standard-dose non-vitamin K antagonists, such as warfarin, may increase the risk of stroke and do not appear to alter the risk of other outcomes, such as any thromboembolic events and major bleeding.

Dr. Ortel concluded with his personal recommendations for the treatment of APS with VTE, which he emphasized must be individualized to the patient. He explained that he treats VTE with anticoagulant therapy, but he avoids direct oral anticoagulants in triple positive APS patients with VTE. He does consider, however, direct oral anticoagulants to be an option for selected APS patients who are not triple positive. He also reminded the audience that selected APS patients with provoked VTE may not need indefinite anticoagulant therapy.

Dr. Ortel then summarized his approach to treating patients with APS with arterial thrombosis, which he believes also must be individualized to the patient. He treats definite APS patients with an initial arterial thrombosis with anticoagulant therapy, although antiplatelet therapy may be an effective alternative for selected patients with an initial arterial event and antiphospholipid antibodies. He avoids direct oral anticoagulants in most APS patients with arterial thrombosis, preferring warfarin over a direct oral anticoagulant in all definite APS patients with arterial thrombosis. He also treats patients for any other risk factors for arterial thrombosis.

Jason S. Knight, MD, PhD, foresees the field becoming more personalized, with rheumatologists treating APS proactively rather than reactively.

Dr. Knight