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Evevident
Original paper
2013NEJMHematology/Oncology

AMPLIFY

Oral apixaban for the treatment of acute venous thromboembolism

RCTVTE

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Overview

Apixaban was noninferior to enoxaparin/warfarin for acute VTE treatment and caused less major bleeding.

Clinical takeaway

AMPLIFY supports apixaban as a single-drug oral treatment strategy for DVT/PE without initial heparin bridging in eligible patients.

Key result

Apixaban was noninferior for recurrent VTE (2.3% vs 2.7%) and roughly halved major bleeding.

Practice impact

DOAC-based VTE treatment replaced heparin-to-warfarin for many eligible patients.

Evidence

Study design

Randomized, double-blind, active-controlled noninferiority trial.

Enrollment

5,395

Follow-up

6 months.

Geography

Multinational

Clinical question

Is apixaban noninferior to conventional therapy for acute VTE, and does it reduce bleeding?

Population

  • Patients with acute symptomatic proximal DVT or pulmonary embolism.

Intervention

Apixaban 10 mg twice daily for 7 days, then 5 mg twice daily, as a single-drug oral regimen.

Comparator

Enoxaparin followed by warfarin (target INR 2-3).

Primary outcome

Recurrent symptomatic VTE or VTE-related death (efficacy); major bleeding (safety).

Single-drug apixaban was noninferior to enoxaparin/warfarin for recurrent VTE and caused significantly less major bleeding.

Relative risk / 0.84 / CI 95% CI 0.60-1.18 / p=<0.001 for noninferiority

Key results

  • Recurrent VTE or VTE-related death: 2.3% with apixaban vs 2.7% with conventional therapy; RR 0.84 (95% CI 0.60-1.18), meeting noninferiority (p<0.001).
  • Major bleeding: 0.6% with apixaban vs 1.8% with conventional therapy; RR 0.31 (95% CI 0.17-0.55; p<0.001).
  • The composite of major and clinically relevant nonmajor bleeding was also markedly lower with apixaban.

Harms

  • Major bleeding was substantially lower with apixaban than with enoxaparin/warfarin.
  • As with all anticoagulants, bleeding remains the principal risk.

Clinical Use

When to cite

  • When selecting oral anticoagulation for acute VTE and discussing apixaban as a no-bridge option with less major bleeding than conventional therapy.

Practice impact

  • DOAC-based VTE treatment replaced heparin-to-warfarin for many eligible patients.

Applicability

  • Most applicable to patients with acute symptomatic proximal DVT or pulmonary embolism.

Limitations

  • Excluded some high-risk groups such as severe renal impairment and certain cancer-associated thrombosis contexts.
  • Adherence is critical with DOAC therapy given the twice-daily regimen.
  • Active-controlled noninferiority design, not a superiority test for efficacy.

Common misinterpretations

  • Apixaban is given as a single oral drug with an initial higher-dose lead-in; no separate parenteral heparin bridge is needed.
  • The efficacy result is noninferiority; the clear superiority is in reduced bleeding, not in preventing recurrence.

Related evidence

ARISTOTLE - Same Drug Class

Citation

Agnelli G, Buller HR, Cohen A, et al. Oral apixaban for the treatment of acute venous thromboembolism. N Engl J Med. 2013;369(9):799-808. doi:10.1056/NEJMoa1302507

A fixed-dose regimen of apixaban alone was noninferior to conventional therapy for the treatment of acute venous thromboembolism and was associated with significantly less bleeding.