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

Disclosures

Rheumatology. 2019;58(6):969-974. 

In This Article

Discussion

In this study, we found that the effectiveness of DAPT as a secondary prophylaxis against arterial thrombosis in APS patients was similar to that of Wf + AP and superior to warfarin alone. The differences in efficacy may be attributed to the constitutional difference in arterial thrombi initiated as platelet aggregates, and venous thrombi consisting mainly of fibrin,[12] with the former being more effectively prevented by anti-platelet agents. The high recurrence rate of cerebral infarction in the Wf monotherapy group is suggestive of this mechanism (Supplementary Table S3, available at Rheumatology online).

Considering that most recurrences took place in the same vascular bed as the original thrombosis, most physicians were choosing secondary prevention therapy including warfarin for the patients with a past history of venous thrombosis (Table 1). In fact, Wf was effective in preventing new venous thrombosis occurrence (recurrence rate: 1.05 per 100 patient-years), but without similar effectiveness for arterial thrombosis (recurrence rate: 10.53 per 100 patient-years). Although the average PT-INR (2.17) herein for the Wf group was lower than those recommended in the guidelines [target PT-INR (2.5–3.5)], this reflects the real world management of warfarin treatment at the time of administration. Previous studies in APS also reported the difficulty in maintaining the optimal PT-INR range without bleeding events.[13]

A systematic review and meta-analysis of DAPT for secondary prevention of myocardial infarction and stroke has shown that long-term use of DAPT was associated with lower mortality compared with other prophylactic regimen.[14] Although treatment-related bleeding events are of serious concern during DAPT, we did not find an increased bleeding risk, most likely due to the younger age of our APS population [median age 45 years (range 31.3–53.0 years)] compared with the non-APS thrombotic population [average age (S.D.): 64.4 (9.5) years].[14] Older age has been reported as a risk of treatment-related bleeding.[15] While aspirin is the most frequently used antiplatelet drug, aspirin has a major disadvantage of aspirin resistance.[16] In fact, aspirin resistance were reported in 27% of patients[17] and was associated with short- and long-term mortality in patients with acute ischaemic stroke.[18] The use of DAPT may be an effective strategy to resolve this issue.

There are some important limitations to be considered in this single-centre Japanese study. Although longitudinal data of at least 2 years in 90 patients is worth reporting, appropriate reproducibility is warranted in a multicentred study. On a similar note, APS patients with diverse ethnic and genetic backgrounds need to be considered. In terms of study design, selection bias inherent to the retrospective observational design warrants further confirmation of the superiority of DAPT in a prospective fashion. Furthermore, the small number of patients on DAPT precluded our comparison among the specific antiplatelet regimens, and the small number of patients on each treatment may contribute to the safety assessment. Although cerebral infarction was confirmed by brain MRI or magnetic resonance angiogram or angiography in all patients, differential diagnosis between cerebral infarction and cerebral vasculitis may be difficult in some patients with SLE and APS due to the diagnostic limitations. Nevertheless, we believe our study will shed light on any prospective clinical study focused on the prophylaxis of arterial thrombosis using DAPT in APS patients.

In conclusion, our results indicate that DAPT might be an effective option for preventing arterial thrombosis in patients with APS.

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