IntroductionThe optimal secondary thromboprophylactic strategies for patients with antiphospholipid syndrome (APS) and arterial thrombosis remain controversial. This study aimed to evaluate the comparative efficacy and safety of various antithrombotic strategies in APS with arterial thrombosis.MethodsA comprehensive literature search was conducted using OVID MEDLINE, EMBASE, Web of Science, and the Cochrane Controlled Register of Trials (CENTRAL) from inception until 30 September 2022, with no language restrictions. The inclusion criteria for eligible studies were as follows: inclusion of APS patients with arterial thrombosis, treatment with either antiplatelet agents, warfarin, direct oral anticoagulants (DOACs), or a combination of these therapies, and reporting of recurrent thrombotic events.ResultsWe conducted a frequentist random-effects network meta-analysis (NMA) involving 13 studies with a total of 719 participants, comprising six randomized and seven non-randomized studies. In comparison to single antiplatelet therapy (SAPT), the combined use of antiplatelet and warfarin demonstrated a significant reduction in the risk of recurrent overall thrombosis, with a risk ratio (RR) of 0.41 (95% CI 0.20 to 0.85). Dual antiplatelet therapy (DAPT) showed a lower risk of recurrent arterial thrombosis compared to SAPT although the difference did not reach statistical significance, with an RR of 0.29 (95% CI 0.08 to 1.07). DOAC was associated with a significant increase in the risk of recurrent arterial thrombosis, with an RR of 4.06 (95% CI 1.33 to 12.40) when compared to SAPT. There was no significant difference in major bleeding among various antithrombotic strategies.DiscussionBased on this NMA, the combination of warfarin and antiplatelet therapy appears to be an effective approach in preventing recurrent overall thrombosis in APS patients with a history of arterial thrombosis. While DAPT may also show promise in preventing recurrent arterial thrombosis, further studies are needed to confirm its efficacy. Conversely, the use of DOACs was found to significantly increase the risk of recurrent arterial thrombosis.

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.

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