Direct Oral Anticoagulants in Patients with Antiphospholipid Syndrome: Results from a Retrospective Study in a Real-life Patient Cohort

Background: The current mainstay for the treatment of thrombotic antiphospholipid syndrome (APS) is anticoagulation with vitamin K antagonists (VKAs). Direct oral anticoagulants (DOACs) have been shown to be effective and safe compared with VKAs in randomized controlled trials, but these results may not be generalizable to patients with APS. Small studies and case series have been published for the use of DOACs in APS patients, with conflicting results. A recent meta-analysis showed that triple antibody positivity may indicate the presence of increased risk of recurrent thrombosis. The ISTH-SSC has suggested avoiding DOACs in patients with APS although there is a general paucity of data.

Methodology: We have conducted a retrospective analysis for the time period from 2010 to 2017 in which we included all patients from our thrombosis clinic with a diagnosis of APS taking either VKAs or DOACs. The diagnosis was based on the revised Sapporo criteria. Monospecific enzyme-linked immunoassays were performed on the Euroimmun analyzer I to identify antiphospholipid antibodies (APA) of the IgG and IgM type against cardiolipin and beta2-glycoprotein-1 (Euroimmun, Lübeck, Germany). Lupus anticoagulant (LA) was identified using LA Screen and LA Confirm reagents from Siemens (Marburg, Germany) on a BCS-XP instrument. Clinical and laboratory data were collected from the electronic and physical patient files. Statistics were calculated using GraphPad Prism 7 software and SPSS 24.

Findings: A total of 290 patients were identified, 12 of which were excluded because a diagnosis of APS could not be confirmed (no or negative second test >12 weeks after the initial test), and 2 others because they attended the clinic only once. In the total cohort of 276 patients, 123 were treated with VKAs, and 153 with DOACs. The two groups did not differ with regard to clinical manifestation (~80% venous and ~20% arterial thromboembolism), sex, presence of LA, and frequency or strength of APAs. Patients with DOACs were significantly older. In the VKA group, there were 5 venous and 2 arterial thrombotic events; in the DOAC group, there were 3 venous and 2 arterial thrombotic events. The total number of patients with any thromboembolic event was 7/123 (5.7%) in the VKA group and 4/153 (2.6%) in the DOAC group. The unadjusted hazard ratio (HR) for any thromboembolic event for patients under DOACs compared with VKA was 0.82 (95% confidence interval, 0.22 to 3.04), and the HR adjusted for age, sex, and triple positivity, was 0.76 (95% confidence interval, 0.20 to 2.87).

Conclusions: We conclude that for patients attending the thrombosis clinic with a confirmed diagnosis of APS, treatment with DOACs does not increase the risk of thromboembolism in comparison to patients treated with VKAs. However, the number of patients with triple antibody positivity in our study was low and an increased risk of thromboembolism under DOAC for this sub-cohort of patients cannot be excluded.

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