Apixaban for the Treatment of Venous Thromboembolism Associated with Cancer

N Engl J Med. 2020 Apr 23;382(17):1599-1607. doi: 10.1056/NEJMoa1915103. Epub 2020 Mar 29.

Abstract

Background: Recent guidelines recommend consideration of the use of oral edoxaban or rivaroxaban for the treatment of venous thromboembolism in patients with cancer. However, the benefit of these oral agents is limited by the increased risk of bleeding associated with their use.

Methods: This was a multinational, randomized, investigator-initiated, open-label, noninferiority trial with blinded central outcome adjudication. We randomly assigned consecutive patients with cancer who had symptomatic or incidental acute proximal deep-vein thrombosis or pulmonary embolism to receive oral apixaban (at a dose of 10 mg twice daily for the first 7 days, followed by 5 mg twice daily) or subcutaneous dalteparin (at a dose of 200 IU per kilogram of body weight once daily for the first month, followed by 150 IU per kilogram once daily). The treatments were administered for 6 months. The primary outcome was objectively confirmed recurrent venous thromboembolism during the trial period. The principal safety outcome was major bleeding.

Results: Recurrent venous thromboembolism occurred in 32 of 576 patients (5.6%) in the apixaban group and in 46 of 579 patients (7.9%) in the dalteparin group (hazard ratio, 0.63; 95% confidence interval [CI], 0.37 to 1.07; P<0.001 for noninferiority). Major bleeding occurred in 22 patients (3.8%) in the apixaban group and in 23 patients (4.0%) in the dalteparin group (hazard ratio, 0.82; 95% CI, 0.40 to 1.69; P = 0.60).

Conclusions: Oral apixaban was noninferior to subcutaneous dalteparin for the treatment of cancer-associated venous thromboembolism without an increased risk of major bleeding. (Funded by the Bristol-Myers Squibb-Pfizer Alliance; Caravaggio ClinicalTrials.gov number, NCT03045406.).

Publication types

  • Equivalence Trial
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Aged
  • Anticoagulants / administration & dosage*
  • Anticoagulants / adverse effects
  • Dalteparin / administration & dosage*
  • Dalteparin / adverse effects
  • Female
  • Hemorrhage / chemically induced*
  • Hemorrhage / epidemiology
  • Humans
  • Incidence
  • Injections, Subcutaneous
  • Intention to Treat Analysis
  • Male
  • Middle Aged
  • Neoplasms / complications*
  • Neoplasms / mortality
  • Proportional Hazards Models
  • Pulmonary Embolism / prevention & control
  • Pyrazoles / administration & dosage*
  • Pyrazoles / adverse effects
  • Pyridones / administration & dosage*
  • Pyridones / adverse effects
  • Secondary Prevention / methods*
  • Single-Blind Method
  • Venous Thromboembolism / drug therapy
  • Venous Thromboembolism / etiology
  • Venous Thromboembolism / prevention & control*
  • Venous Thrombosis / prevention & control

Substances

  • Anticoagulants
  • Pyrazoles
  • Pyridones
  • apixaban
  • Dalteparin

Associated data

  • ClinicalTrials.gov/NCT03045406