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

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.

Apixaban for Routine Management of Upper Extremity Deep Venous Thrombosis (ARM-DVT): Methods of a prospective single-arm management study.

BACKGROUND: Upper extremity deep vein thrombosis (UEDVT) constitutes approximately 10% of all deep vein thromboses (DVTs). The incidence of UEDVT is increasing in association with use of peripherally inserted central venous catheters. Treatment for UEDVT is derived largely from evidence for treatment of lower extremity DVT. Limited evidence exists for the use of a direct oral anticoagulant for the treatment of UEDVT. POPULATION: Sequential patients identified within the Intermountain Healthcare System and University of Utah Healthcare system with symptomatic UEDVT defined as the formation of thrombus within the internal jugular, subclavian, axillary, brachial, ulnar, or radial veins of the arm. INTERVENTION: Apixaban 10 mg PO twice daily for 7 days followed by apixaban 5 mg twice daily for 11 weeks. COMPARISON: The historical literature review rate of venous thrombosis reported for recurrent clinically overt objective venous thromboembolism (VTE) and VTE-related death. If the confidence interval for the observed rate excludes the threshold event rate of 4%, we will conclude that treatment with apixaban is noninferior and therefore a clinically valid approach to treat UEDVT. SAMPLE SIZE: We elected a sample size of 375 patients so that an exact 95% confidence interval would exclude an event rate of VTE in the observation cohort of 4%. OUTCOME: Ninety-day rate of new or recurrent objectively confirmed symptomatic venous thrombosis and VTE-related death. The primary safety outcome is the composite of major and clinically relevant nonmajor bleeding.