Efficacy of Dual Antiplatelet Therapy for Preventing Recurrence of Arterial Thrombosis in Patients With Antiphospholipid Syndrome

Naoki Ohnishi; Yuichiro Fujieda; Ryo Hisada; Hiroyuki Nakamura; Masaru Kato; Kenji Oku; Toshiyuki Bohgaki; Olga Amengual; Shinsuke Yasuda; Tatsuya Atsumi


Rheumatology. 2019;58(6):969-974. 

In This Article

Abstract and Introduction


Objective: Warfarin is regarded as the standard treatment for preventing thrombotic events in APS, but the recurrence rate is still high. Dual antiplatelet therapy (DAPT) has been shown to be effective for the prevention of acute coronary syndrome or stroke. The objective of this study was to evaluate the efficacy of DAPT for the prevention of thrombosis recurrence in APS patients with history of arterial thrombosis.

Methods: This retrospective cohort study of APS patients was conducted at Hokkaido University Hospital between 1990 and 2016. The secondary prophylactic effects and safety of warfarin monotherapy (Wf), antiplatelet monotherapy (AP), warfarin and antiplatelet combination therapy (Wf + AP) and DAPT were evaluated. The primary endpoints were set as thrombosis-free and adverse events-free survival period. Adverse events were defined as severe bleeding and death.

Results: A total of 90 APS patients were enrolled. Thrombotic recurrence was found in 40 patients (35 arterial and 5 venous thromboses) and serious adverse events in 20 patients (9 severe bleeding events and 14 deaths). Kaplan–Meier analysis demonstrated a 10-year recurrence-free survival rate of 62%. The recurrence rate per 100 patient-years was as follows: Wf: 11.6, AP: 5.5, Wf: + AP: 3.7, DAPT: 1.8. We demonstrated that DAPT significantly reduced the rate of recurrence compared with Wf (log-rank P = 0.001). There were no significant differences in the rate of serious adverse events among the groups.

Conclusion: DAPT might be considered as an effective and safe option for the prophylaxis of recurrent arterial thrombosis in APS.


APS is an autoimmune disease characterized by thrombotic events and pregnancy complications with persistently positive aPL.[1] APS patients suffer from thrombosis in both arteries and veins, while protein C deficiency, Factor V Leiden, and other thrombophilia mostly affect the venous circulation.

According to the guidelines for the management of patients with APS, anticoagulation using warfarin is recommended for secondary prophylaxis of arterial/venous thrombosis by targeting the PT-International normalized ratio (PT-INR) between 2.0 and 3.0.[2] On the other hand, the APS Workshop guidelines recommend that APS patients with an arterial thrombotic event should be treated with warfarin at PT-INR >3.0 or with antiplatelet plus warfarin combination therapy at PT-INR between 2.0 and 3.0.[3] The difference between these recommendations may be due to the discrepancy in their main objectives of avoiding treatment-related bleeding events[4] or preventing severe recurrent thrombosis.[5] However, a major limitation in both recommendations is that there is no definitive evidence of prevention of recurrent arterial events.

Dual antiplatelet therapy (DAPT) is commonly used in clinical practice for the secondary prevention of arterial thrombotic events in patients at high recurrence risk. Defined as the combination of aspirin and a P2Y12-receptor inhibitor, DAPT has demonstrated superior efficacy over anticoagulant therapy in coronary artery disease. Although there have been no reports of retrospective/prospective studies that compare the effectiveness and safety of DAPT in APS patients,[6] the benefit of antiplatelet therapy is highly suggestive as most arterial thromboses recur as arterial thrombosis.[7,8] Although arterial thrombosis in APS is reported most frequently in Japan compared with other countries, still the low prevalence of disease makes prospective trials very difficult.[5,8] Therefore, our longitudinal APS cohort was used to evaluate the benefit of DAPT in patients with a history of arterial thrombosis.