Extending venous thromboembolism secondary prevention with apixaban in cancer patients. The EVE trial

J Thromb Haemost. 2024 Jun;22(6):1704-1714. doi: 10.1016/j.jtha.2024.03.011. Epub 2024 Mar 25.

Abstract

Background: Cancer-associated venous thromboembolism (VTE) management guideline recommendations include continued therapeutic anticoagulation while active cancer persists. The Federal Drug Administration label for apixaban for secondary VTE prevention includes a dose reduction to 2.5 mg twice daily after 6 months of treatment.

Objectives: The study's purpose was to determine whether this dose reduction is advisable for cancer-associated VTE.

Methods: A randomized, double-blind trial compared apixaban 2.5 mg with 5 mg twice daily for 12 months among cancer patients with VTE who had completed 6 to 12 months of anticoagulation therapy. The primary outcome was combined major bleeding plus clinically relevant nonmajor bleeding.

Results: Of 370 patients recruited, 360 were included in the intention-to-treat analyses. Major plus clinically relevant nonmajor bleeding occurred in 16 of 179 patients (8.9%) in the apixaban 2.5 mg group compared with 22 of 181 patients (12.2%) in the 5 mg group (hazard ratio [HR], 0.72; 95% CI, 0.38-1.37; P = .39). Major bleeding occurred in 2.8% of the apixaban 2.5 mg group and in 2.2% of the 5 mg group (HR, 1.26; 95% CI, 0.34-4.66; P = .73). Recurrent VTE or arterial thrombosis occurred in 9 of 179 patients (5.0%) in the apixaban 2.5 mg group and 9 of 181 patients (5.0%) in the 5 mg group (HR, 1.0; 95% CI, 0.40-2.53; P = 1.00). All-cause mortality rates were similar between groups, 13% vs 12% (HR, 1.14; 95% CI, 0.63-2.04; P = .67).

Conclusion: For secondary prevention of cancer-associated VTE, apixaban 2.5 mg compared with 5 mg twice daily did not lower combined bleeding events (EVE trial NCT03080883).

Keywords: apixaban; cancer; secondary prevention; venous thromboembolism.

Publication types

  • Randomized Controlled Trial
  • Multicenter Study

MeSH terms

  • Aged
  • Anticoagulants / administration & dosage
  • Anticoagulants / adverse effects
  • Anticoagulants / therapeutic use
  • Double-Blind Method
  • Drug Administration Schedule
  • Factor Xa Inhibitors* / administration & dosage
  • Factor Xa Inhibitors* / adverse effects
  • Factor Xa Inhibitors* / therapeutic use
  • Female
  • Hemorrhage* / chemically induced
  • Humans
  • Male
  • Middle Aged
  • Neoplasms* / complications
  • Neoplasms* / drug therapy
  • Pyrazoles* / administration & dosage
  • Pyrazoles* / adverse effects
  • Pyridones* / administration & dosage
  • Pyridones* / adverse effects
  • Risk Factors
  • Secondary Prevention*
  • Time Factors
  • Treatment Outcome
  • Venous Thromboembolism* / diagnosis
  • Venous Thromboembolism* / drug therapy
  • Venous Thromboembolism* / etiology
  • Venous Thromboembolism* / mortality
  • Venous Thromboembolism* / prevention & control

Substances

  • Pyridones
  • apixaban
  • Pyrazoles
  • Factor Xa Inhibitors
  • Anticoagulants

Associated data

  • ClinicalTrials.gov/NCT03080883