Background
Phase III open-label RCT (TRAPS), N=120, age 18-75 with high-risk triple-positive antiphospholipid syndrome and prior thrombosis (arterial, venous, or biopsy-proven microthrombosis). Randomized to rivaroxaban vs warfarin. Triple positivity = lupus anticoagulant + anti-cardiolipin IgG/IgM (>40 GPL/MPL or >99th percentile) + anti-β2-glycoprotein I IgG/IgM (>40 U or >99th percentile). Exclusions: pregnancy, CrCl <30 mL/min, cirrhosis or LFT >3×ULN, high bleeding risk. Terminated early for excess thromboembolism with rivaroxaban.
Interventions and follow up
Arm A: rivaroxaban 20 mg daily (15 mg if CrCl 30-50 mL/min)
Arm B: warfarin, INR 2.0-3.0
Primary endpoint: composite of thromboembolic events, major bleeding, and vascular death
mFollow up: stopped at 1.5 yr for increased composite outcome
Arm B: warfarin, INR 2.0-3.0
Primary endpoint: composite of thromboembolic events, major bleeding, and vascular death
mFollow up: stopped at 1.5 yr for increased composite outcome
Results
Composite (thromboembolism, major bleeding, vascular death), A vs B: 19% vs 3%
Arterial thrombosis: 12% vs 0 (ischemic stroke 7% vs 0; MI 5% vs 0)
Major bleeding: 7% vs 3%, HR 2.5, 95%CI 0.5-13.6, P=.3
Venous thrombosis: none in either arm
Arterial thrombosis: 12% vs 0 (ischemic stroke 7% vs 0; MI 5% vs 0)
Major bleeding: 7% vs 3%, HR 2.5, 95%CI 0.5-13.6, P=.3
Venous thrombosis: none in either arm
Adverse events
Thromboembolic events: 7 with rivaroxaban (4 ischemic stroke, 3 MI) vs 0 with warfarin
Major bleeds: 4 with rivaroxaban vs 2 with warfarin
Trial status: halted prematurely for harm in the DOAC arm
Major bleeds: 4 with rivaroxaban vs 2 with warfarin
Trial status: halted prematurely for harm in the DOAC arm
Conclusions
In high-risk triple-positive antiphospholipid syndrome, rivaroxaban was associated with increased arterial thrombosis and bleeding vs warfarin. DOACs should be avoided in this population.
Key Limitations
Open-label; small N; terminated early (overestimates effect); restricted to triple-positive high-risk APS, limiting generalizability to lower-risk single/double-positive patients.
Clinical Context
TRAPS, alongside the Ordi-Ros and other APS-DOAC trials, establishes vitamin K antagonists (warfarin) as standard anticoagulation for thrombotic APS. ISTH and EULAR guidance recommends against DOACs in triple-positive APS.