DOACs: risk of recurrent thrombotic events in patients with antiphospholipid syndrome


  • Drug Updates
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Direct-acting oral anticoagulants (DOACs) indicated for treatment and prevention of venous thromboembolism (VTE) and prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation with one or more risk factors. DOACs available are apixaban, dabigatran etexilate, edoxaban, and rivaroxaban.

An EU review has concluded that use of DOACs in patients with antiphospholipid syndrome could be associated with increased rates of recurrent thrombotic events compared with therapy with a vitamin K antagonist.

The level of evidence for an increased risk of recurrent thrombotic events in patients with antiphospholipid syndrome differs among DOACs. However, DOACs are not recommended in patients with antiphospholipid syndrome, particularly high-risk patients (those who test positive for all 3 antiphospholipid tests: lupus anticoagulant, anticardiolipin antibodies, and anti-beta 2 glycoprotein I antibodies). Changes are therefore being made to the product information for these medicines to advise that use of DOACs in these patients with antiphospholipid syndrome is not recommended.

In an open-label, randomised, multicentre (TRAPS) study with blinded endpoint adjudication. Outcomes with rivaroxaban were compared with warfarin in patients with antiphospholipid syndrome and a history of thrombosis, and at high risk for thromboembolic events (patients who persistently tested positive for all 3 antiphospholipid tests).

The trial was terminated prematurely after the enrolment of 120 patients due to an excess of thromboembolic events among patients in the rivaroxaban arm. Follow-up, 569 days. In the study, 59 patients were randomly assigned to rivaroxaban 20 mg (15 mg dose for patients with creatinine clearance

Thromboembolic events occurred in 12% of patients assigned to receive rivaroxaban. No thromboembolic events were reported in patients assigned to receive warfarin. Major bleeding events occurred in 4 patients in rivaroxaban group and 2 patients in warfarin group. No deaths were reported.

Available data for apixaban, edoxaban and dabigatran etexilate are more limited than for rivaroxaban because there have been no completed clinical trials of these products in patients with antiphospholipid syndrome. However, available data suggest these other DOACs may be associated with a similarly increased risk of recurrent thrombotic events as with use of rivaroxaban.

Healthcare professionals are advised to report suspected adverse drug reactions to DOACs including any thromboembolic events suspected to be due to lack of efficacy via the Yellow Card Scheme.