Direct oral anticoagulants in antiphospholipid syndrome: Meta-analysis of randomized controlled trials

Abstract

Background: The gold standard for secondary thromboprophylaxis in APS is long term anticoagulation with vitamin K antagonists (VKAs). Because of their widespread use and potential advantages of directs oral anticoagulants (DOACs) over VKAs, they have been prescribed in APS without definitive evidence of their safety and efficacy in this context. Recent specific randomized controlled trials (RCT) in APS and results from pivotal RCTs comparing DOACs vs VKAs are now available. Their results are conflicting but these studies have been conducted in different APS populations.

Purpose of review: To summarize available data from RCT and determine risks of recurrent thrombosis and bleeding.

Results: Four studies were included and 23 and 10 thrombotic events were recorded among 282 and 294 APS patients treated with DOACs and warfarin respectively. Overall recurrent thrombotic events were not significantly increased during DOACs treatment (OR = 2.22 [95% CI, 0.58-8.43]) compared to VKAs. However, when different types of thrombosis were analyzed separately, there was an increased risk of recurrent arterial thrombosis (5.17 [95% CI, 1.57-17.04]) with DOACs compared to warfarin but no significant higher risk of venous thrombosis (OR 0.69 [95% CI, 0.23-2.06). No increased risk of bleeding was found.

In conclusion: In APS patients treated with DOACs compared to those treated with warfarin, no evidence of a higher risk of recurrent venous thromboembolism was found however there was a significantly increased risk of recurrent arterial thrombosis. Moreover risk of recurrent arterial thrombosis tended to be more frequent in patients with a history of arterial thrombosis. These results are in line with international guidelines which recommend not to use DOACs in APS patients with a history of arterial thrombosis but raise the question of the efficacy of DOACs to prevent venous thrombosis in a subset of APS patients without a history of arterial thrombosis.

Keywords: Antiphospholipid antibodies; Antiphospholipid syndrome; Arterial thrombosis; Direct oral anticoagulants; Randomized controlled trial; Rivaroxaban.