Direct oral anticoagulants: an alternative treatment for thrombotic antiphospholipid syndrome?

Abstract

Background Direct oral anticoagulants (DOACs) demonstrate a lower risk-benefit ratio than vitamin K antagonists (VKAs) for secondary thromboprophylaxis of thrombotic events. But there are no data on the efficacy of DOACs for the prevention of thrombotic recurrence in patients with antiphospholipid syndrome (APS). In this study, we evaluated the efficacy of DOACs to prevent recurrences of thrombotic events in patients with APS. Methods This was a single-center pilot, using a multi-step Fleming design. If seven or fewer patients presented treatment failure with rivaroxaban, the study could conclude efficacy. Results A total of 23 patients were included. APS involved the veins only ( n = 19), arteries only ( n = 2) or both ( n = 1) and 1 patient exhibited catastrophic antiphospholipid syndrome (CAPS). Overall, two patients were positive for lupus anticoagulant, anti-beta-2 glycoprotein I antibodies and anticardiolipid antibodies (triple positivity). The mean duration of follow up was 35.6 (range, 29-40) months. A total of six treatment failures were reported: one patient, with triple positivity, developed bilateral distal pulmonary embolism (PE) after 20 months of treatment with rivaroxaban, two patients refused to take rivaroxaban, the treatment was stopped in three other patients: two with adverse effects and one with chronic iron-deficiency anemia. Conclusions Rivaroxaban may represent an alternative for secondary thromboprophylaxis for thrombo-embolism in patients with APS, in particular, those with poor international normalized ratio (INR) control and those who are not at the highest risk of recurrent thrombosis, such as those with triple positivity.

Direct oral anticoagulants in patients with venous thromboembolism and thrombophilia: a systematic review and meta‐analysis

“…Approximately 203 APS patients treated with DOACs have been reported in various case series, in which rates of VTE recurrence ranged between 0% and 75% after a median follow up of 10-35 months. More than 50% of these recurrences occurred among patients with triple positivity [40][41][42]44,45,48,49,53,54]. Similar observation of a 3.5-fold increased risk of thrombotic recurrence with triple-antibody positivity (P = .03) was made by a 2016 systematic review of DOAC use in APS patients [55].…”

Use of direct oral anticoagulants in antiphospholipid syndrome

“…The case series and cohort studies on DOAC use in APS patients suggest that recurrent thrombotic events with standard‐intensity DOACs in APS patients mainly occur when DOACs are used for secondary prevention of APS‐related arterial or microvascular thrombosis , when DOACs are unlicensed . We believe that these patient groups should not be treated with DOACs until further trial data are available.…”

“…Warfarin-treated APS patients with previous VTE, with or without SLE, were randomized 1 : 1 to warfarin or rivaroxaban, 20 mg once daily, stratified by center and SLE/non-SLE. Table 1 Case series and cohort studies in which thrombotic antiphospholipid syndrome patients treated with direct oral anticoagulants (DOACs) developed recurrent thrombosis Case series [67] Case series [68] Case series [69] Cohort [70] Cohort [71] Case series [72] No The primary outcome measure was percentage change in ETP in the TG assay from randomization to day 42, with treatment continued for 180 days and follow-up for 210 days. One hundred and sixteen patients were randomized, of whom 19% had SLE.…”

“…It is of note that the major phase 3 clinical trials that established the use of DOACs versus warfarin for the treatment and secondary preven- suggests that rivaroxaban might be useful in selected APS patients with single venous thrombosis requiring standard intensity anticoagulation; however, this needs to be confirmed with additional studies using clinical outcome measures' [7]. The case series and cohort studies on DOAC use in APS patients suggest that recurrent thrombotic events with standard-intensity DOACs in APS patients mainly occur when DOACs are used for secondary prevention of APS-related arterial or microvascular thrombosis [67][68][69][70][71][72], when DOACs are unlicensed [8][9][10][11]. We believe that these patient groups should not be treated with DOACs until further trial data are available.…”

Antiphospholipid Syndrome and the Neurologist: From Pathogenesis to Therapy

“…To date, antithrombotic therapy represents the cornerstone of APS management. This is primarily based on vitamin K antagonists (VKA), generally warfarin ( 108 ). The high risk of thrombosis recurrence, which can be seen in 5–16% of subjects ( 109 ), warrants long-term anticoagulation.…”