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ASTRO-APS

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

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Year of Publication: 2022

Authors: Scott C. Woller, Scott M. Stevens, David Kaplan, ..., C. Greg Elliott

Journal: Blood Advances

Citation: Woller SC, Stevens SM, Kaplan D, et al. Blood Adv. 2022 Mar 22;6(6):1661–1670.

Link: https://doi.org/10.1182/bloodadvances.2021005808

Clinical Question

Is apixaban a safe and effective alternative to warfarin for preventing recurrent thrombosis in patients with thrombotic antiphospholipid syndrome (TAPS)?

Bottom Line

In this small pilot RCT, apixaban was associated with a higher rate of ischemic stroke compared to warfarin among patients with TAPS, leading to early study termination and reinforcing concerns that DOACs may not be suitable alternatives to warfarin in this population.

Major Points

  • Multicenter PROBE-design trial comparing apixaban and warfarin in 48 patients with thrombotic APS (TAPS).
  • Trial was terminated early after 6 strokes occurred in apixaban group vs 0 in warfarin group.
  • Two protocol changes: (1) apixaban dose increased from 2.5 mg to 5 mg BID, (2) exclusion of patients with history of arterial thrombosis.
  • No major or clinically relevant non-major bleeds occurred in apixaban group; 1 major bleed in warfarin group.
  • Patients on apixaban reported significantly higher satisfaction with anticoagulation therapy across all time points.

Design

Study Type: Randomized, open-label, blinded-endpoint (PROBE)

Randomization: 1

Blinding: Blinded outcome adjudication

Enrollment Period: February 2015 – March 2019

Follow-up Duration: 12 months

Centers: 2

Countries: United States

Sample Size: 48

Analysis: Intention-to-treat, as-treated, and person-time analyses

Inclusion Criteria

  • Adults with thrombotic antiphospholipid syndrome (TAPS)
  • Receiving therapeutic anticoagulation for ≥6 months
  • Classified as definite, likely, or historical APS per Sapporo criteria

Exclusion Criteria

  • Anticoagulation for another indication
  • Dual antiplatelet therapy or aspirin >165 mg/day
  • Pregnancy or intent to become pregnant
  • Life expectancy <1 year
  • Baseline hemoglobin <8 g/dL, platelets <50,000/µL, creatinine >2.5 mg/dL, total bilirubin >1.5x ULN
  • Thrombosis while on therapeutic warfarin (INR ≥2.0)

Arms

FieldApixabanControl
InterventionApixaban 2.5 mg BID initially; increased to 5 mg BID mid-trial per DSMB recommendationWarfarin with target INR 2–3, managed per clinical routine
Duration12 months12 months

Outcomes

OutcomeTypeControlInterventionHR / OR / RRP-value
Composite of clinically overt thrombosis and vascular deathPrimary0 events6 ischemic strokes
Major bleedingSecondary1 event (vaginal hemorrhage)0 events
Patient satisfaction (ACTS)SecondaryLower scores at all time pointsHigher scores at all time points<0.01
Ischemic StrokeAdverse06
Major BleedAdverse10

Subgroup Analysis

After excluding patients with prior arterial thrombosis, 2 strokes still occurred in apixaban arm (n=17) vs 0 in warfarin (n=16); trend persisted across both apixaban doses (2.5 mg and 5 mg).

Criticisms

  • Early termination due to safety concerns and funding loss
  • Small sample size (n=48) limited statistical power
  • Multiple protocol changes (dose escalation, exclusion of arterial thrombosis)
  • Open-label design may introduce bias despite blinded adjudication
  • Results not generalizable due to heterogeneous cohort and limited site participation

Funding

Investigator-initiated funding from Bristol-Myers-Squibb/Pfizer paid to Intermountain Healthcare

Based on: ASTRO-APS (Blood Advances, 2022)

Authors: Scott C. Woller, Scott M. Stevens, David Kaplan, ..., C. Greg Elliott

Citation: Woller SC, Stevens SM, Kaplan D, et al. Blood Adv. 2022 Mar 22;6(6):1661–1670.

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