Antithrombotic strategies in antiphospholipid syndrome with arterial thrombosis: a systematic review and network meta-analysis

Abstract

Background There was still a lack of consensus regarding optimal antithrombotic strategies in Antiphospholipid syndrome (APS) with arterial thrombosis. Purpose This Systematic review and Network meta-analysis (NMA) were conducted to evaluate the relative efficacy and safety of secondary thromboprophylaxis strategies in this setting. Methods We searched OVID MEDLINE, Web of Science and the Cochrane Controlled Register of Trials (CENTRAL) from inception to the March 1, 2022 without language restriction. Eligible studies were: i) included APS with arterial thrombosis; ii) treated with any of antiplatelet, warfarin, direct oral anticoagulants (DOACs) or a combination of those treatments, and iii) reported recurrent thrombotic events. Case reports or small studies which included less than 5 patients in each arm were excluded. Two investigators independently abstracted data and assessed risk of bias of included studies. A frequentist random-effects network meta-analysis was performed. All results were analyzed using the netmeta package in R, version 3.6.2. Results The database search resulted in 4076 results. After screening, 3998 studies were excluded. A total of 78 studies were included in full-text reviews. Finally, there were 12 studies (6 randomized and 6 non-randomized studies) included in this network meta-analysis, comprising 681 participants. Dual antiplatelet therapy (DAPT) and combined antiplatelet with warfarin were associated with lower risk of recurrent thrombosis with odds ratio (OR) 0.16 (95% CI 0.03 to 0.90) and 0.25 (95% CI 0.08 to 0.78) respectively comparing to single antiplatelet therapy (SAPT). DOACs and moderate-intensity warfarin were associated with higher recurrent arterial thrombosis with OR 12.59 (95% CI 2.03 to 78.19) and 5.25 (95% CI 1.17 to 23.48) respectively. There was no significant different major bleeding risk among antithrombotic regimens. The certainty of the evidences was very-low for all outcomes. Conclusion This network meta-analysis shows that a combination of antiplatelet with warfarin and DAPT were relatively effective antithrombotic strategies secondary prevention of recurrent thrombosis in arterial-thrombotic APS as compared to SAPT. However, there was still limited quality of evidence. Funding Acknowledgement Type of funding sources: None.