Background
Phase 3 double-blind, double-dummy RCT (AMPLIFY). 5,395 patients with acute symptomatic DVT or PE. Compared apixaban (single-drug oral approach with initial high-dose phase) versus conventional therapy (enoxaparin bridged to warfarin). Apixaban is an oral direct factor Xa inhibitor. Designed as a non-inferiority study for recurrent VTE. Note: AMPLIFY CLL (Tam NEJM 2025) is a separate, unrelated trial in this database (n=492); this entry covers the VTE indication.
Interventions and follow up
Arm A: Apixaban 10 mg twice daily × 7 days, then 5 mg twice daily for 6 month
Arm B: Enoxaparin 1 mg/kg twice daily × ≥5 days + warfarin (target INR 2.0–3.0) for 6 month
Primary endpoint: Recurrent symptomatic VTE or VTE-related death — non-inferiority margin 1.80 for risk ratio upper CI
mFollow up: 6 month
Arm B: Enoxaparin 1 mg/kg twice daily × ≥5 days + warfarin (target INR 2.0–3.0) for 6 month
Primary endpoint: Recurrent symptomatic VTE or VTE-related death — non-inferiority margin 1.80 for risk ratio upper CI
mFollow up: 6 month
Results
Recurrent VTE or VTE-related death: 2.3% (apixaban) vs 2.7% (enoxaparin/warfarin); RR 0.84, 95% CI 0.60–1.18 — non-inferior (P<.001)
Major bleeding: 0.6% vs 1.8%; RR 0.31, 95% CI 0.17–0.55 — P<.001 (superiority)
Clinically relevant non-major bleeding: 3.8% vs 8.0%; RR 0.44, 95% CI 0.36–0.55
Net clinical outcome (VTE + major bleeding): 3.0% vs 4.8%; RR 0.62 (P<.001)
Major bleeding: 0.6% vs 1.8%; RR 0.31, 95% CI 0.17–0.55 — P<.001 (superiority)
Clinically relevant non-major bleeding: 3.8% vs 8.0%; RR 0.44, 95% CI 0.36–0.55
Net clinical outcome (VTE + major bleeding): 3.0% vs 4.8%; RR 0.62 (P<.001)
Adverse events
Main adverse events: Major bleeding 69% lower with apixaban vs enoxaparin/warfarin (0.6% vs 1.8%; P<.001). Clinically relevant non-major bleeding also markedly reduced (3.8% vs 8.0%). No intracranial or fatal bleeds with apixaban vs 4 with enoxaparin/ warfarin. Overall bleeding reduction was more pronounced than in rivaroxaban trials.
Conclusions
Apixaban was non-inferior to enoxaparin/warfarin for acute VTE treatment and caused significantly less major and overall bleeding, with a highly favorable net clinical benefit, establishing the single-drug oral approach as the preferred treatment for acute VTE.
Key Limitations
Key Limitations: Double-blind double-dummy design is methodologically rigorous but complex. Fixed 6-month treatment duration — longer-term data needed. Warfarin TTR (time in therapeutic range) was 61% — better than many real-world cohorts, which may underestimate relative benefit in settings with poor INR control. DVT and PE were pooled — the PE-only subgroup was smaller. Cancer patients were a minority (~3%).
Clinical Context
AMPLIFY (VTE) and its extension trial AMPLIFY-EXT led to FDA approval of apixaban for acute VTE treatment and extended prophylaxis (2014). Apixaban has the most favorable bleeding data among DOACs for acute VTE and is widely preferred in clinical practice. Head-to-head data comparing DOACs directly are limited; choice among DOACs is largely based on tolerability, dosing convenience, and cost.
References