Apixaban compared with warfarin to prevent thrombosis in thrombotic antiphospholipid syndrome: a randomized trial

Abstract

Thrombotic antiphospholipid syndrome (TAPS) is characterized by venous, arterial, or microvascular thrombosis. Patients with TAPS merit indefinite anticoagulation, and warfarin has historically been the standard treatment. Apixaban is an oral factor Xa inhibitor anticoagulant that requires no dose adjustment or monitoring. The efficacy and safety of apixaban compared with warfarin for TAPS patients remain unknown. This multicenter prospective randomized open-label blinded endpoint study assigned anticoagulated TAPS patients to apixaban or warfarin (target international normalized ratio 2-3) for 12 months. The primary efficacy outcome was clinically overt thrombosis and vascular death. Apixaban was first given at 2.5 mg twice daily. Two protocol changes were instituted based on recommendations from the data safety monitoring board. After the twenty-fifth patient was randomized, the apixaban dose was increased to 5 mg twice daily, and after the thirtieth patient was randomized, subjects with prior arterial thrombosis were excluded. Primary outcomes were adjudicated by independent experts blinded to treatment allocation. Patients randomized between 23 February 2015 and 7 March 2019 to apixaban (n = 23) or warfarin (n = 25) were similar. Among the components of the primary efficacy outcome, only stroke occurred in 6 of 23 patients randomized to apixaban compared with 0 of 25 patients randomized to warfarin. The study ended prematurely after the forty-eighth patient was enrolled. Conclusions from our study are limited due to protocol modifications and low patient accrual. Despite these limitations, our results suggest that apixaban may not be routinely substituted for warfarin to prevent recurrent thrombosis (especially strokes) among patients with TAPS. This trial was registered at www.clinicaltrials.gov as #NCT02295475.

Graphical abstract

Figure 1.

Consort diagram of patients screened. One MRI screen fail was because of the identification of a brain tumor, and the other was because the patient had white matter changes disproportionate for age. MRI, magnetic resonance imaging.

Figure 2.

Kaplan-Meier cumulative event rate for thrombosis. The solid red line is for apixaban, and the solid blue line is for warfarin.

Figure 3.

Assessment of patient satisfaction with anticoagulation treatment using ACTS among patients randomized to apixaban or warfarin. Shown is a comparison of patient satisfaction with anticoagulation treatment assessment measured with a validated assessment tool (ACTS) at the shown time points. The midline in each box represents the median, and the top and the bottom of each box represent the cutoffs of the interquartile range. The whiskers represent 1.5 times the interquartile range, and outliers are represented as dots. Apixaban was significantly favored over warfarin at every interval assessment.