Net-clinical benefit of extended prophylaxis of venous thromboembolism with betrixaban in medically ill patients aged 80 or more

J Thromb Haemost. 2019 Dec;17(12):2089-2098. doi: 10.1111/jth.14600. Epub 2019 Aug 26.

Abstract

Background: Extended-duration thromboprophylaxis with betrixaban reduces the risk of venous thromboembolism (VTE) without increasing major bleeding rates in acutely ill medical patients as compared to standard duration enoxaparin. We aimed to assess the risk-benefit of betrixaban in patients aged ≥ 80 years enrolled in the APEX trial.

Methods: APEX was a randomized, double-blind trial in which patients hospitalized for acute medical illnesses received enoxaparin 40 mg qd for 10 ± 4 days or oral betrixaban 80 mg qd for 35 to 42 days. The primary efficacy outcome was VTE, the principal safety outcome was major bleeding. Net clinical benefit (NCB) was defined by the occurrence of VTE or major bleeding.

Results: Of 7513 patients enrolled in the APEX trial, 2781 (37%) were aged ≥ 80 years. In this subgroup, VTE or major bleeding occurred in 7.0% of betrixaban patients and in 8.4% of enoxaparin patients, for a relative risk in the NCB of 0.82 (95% confidence interval 0.62-1.10). The relative risk reduction obtained with betrixaban was similar between those aged ≥ 80 years and patients younger than 80 years (5.0% and 6.7%, respectively, NCB 0.75, 0.58-0.96, P = .024), with no significant interaction across age groups (P = .33).

Conclusions: Event rates were higher in medically ill patients aged ≥ 80 years enrolled in the APEX study than in patients younger than 80 years. The predefined NCB was reduced with extended betrixaban therapy in both groups with no signs of age-related interactions. However, the primary efficacy endpoint was not achieved with betrixaban for patients 80 years of age or older.

Keywords: betrixaban; elderly; medical patients; prophylaxis; venous thromboembolism.

Publication types

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

MeSH terms

  • Administration, Oral
  • Adult
  • Aged
  • Aged, 80 and over
  • Anticoagulants / administration & dosage*
  • Anticoagulants / adverse effects
  • Benzamides / administration & dosage*
  • Benzamides / adverse effects
  • Blood Coagulation / drug effects*
  • Double-Blind Method
  • Drug Administration Schedule
  • Enoxaparin / administration & dosage*
  • Enoxaparin / adverse effects
  • Factor Xa Inhibitors / administration & dosage*
  • Factor Xa Inhibitors / adverse effects
  • Female
  • Hemorrhage / chemically induced
  • Humans
  • Male
  • Middle Aged
  • Progression-Free Survival
  • Pyridines / administration & dosage*
  • Pyridines / adverse effects
  • Risk Assessment
  • Risk Factors
  • Time Factors
  • Venous Thromboembolism / blood
  • Venous Thromboembolism / etiology
  • Venous Thromboembolism / mortality
  • Venous Thromboembolism / prevention & control*

Substances

  • Anticoagulants
  • Benzamides
  • Enoxaparin
  • Factor Xa Inhibitors
  • Pyridines
  • betrixaban