Clinical Impact of Bleeding in Cancer-Associated Venous Thromboembolism: Results from the Hokusai VTE Cancer Study

Thromb Haemost. 2018 Aug;118(8):1439-1449. doi: 10.1055/s-0038-1667001. Epub 2018 Jul 30.

Abstract

In the Hokusai VTE Cancer study, edoxaban was non-inferior to dalteparin for the composite outcome of recurrent venous thromboembolism (VTE) and major bleeding in 1,050 patients with cancer-associated VTE. The absolute rate of recurrent VTE was 3.4% lower with edoxaban, whereas the absolute rate of major bleeding was 2.9% higher. The present analysis focuses on the sites, clinical presentation, course and outcome of bleeding events, and the associated tumour types. Major bleeds and their severity (categories 1-4) were blindly adjudicated by a committee using a priori defined criteria, and data were analysed in the safety population. Major bleeding occurred in 32 of 522 patients given edoxaban (median treatment duration, 211 days) and in 16 of 524 patients treated with dalteparin (median treatment duration, 184 days); no patients had more than one major bleed. There were no fatal bleeds with edoxaban, and two with dalteparin. Severe bleeding at presentation (category 3 or 4) occurred in 10 (1.9%) and 11 (2.1%) patients in the edoxaban and dalteparin groups, respectively. The excess of major bleeding with edoxaban was confined to patients with gastrointestinal cancer. However, severe major bleeding at presentation (category 3 or 4) in this sub-group occurred in 5 of 165 (3.0%) and in 3 of 140 (2.1%) patients given edoxaban or dalteparin, respectively.In conclusion, this analysis suggests that while oral edoxaban is an appropriate alternative to subcutaneous dalteparin for treatment of cancer-associated VTE, the use of edoxaban in patients with gastrointestinal cancer requires careful benefit-risk weighting.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Anticoagulants / administration & dosage
  • Anticoagulants / adverse effects*
  • Clinical Decision-Making
  • Dalteparin / administration & dosage
  • Dalteparin / adverse effects*
  • Factor Xa Inhibitors / administration & dosage
  • Factor Xa Inhibitors / adverse effects*
  • Female
  • Hemorrhage / chemically induced*
  • Hemorrhage / diagnosis
  • Humans
  • Male
  • Middle Aged
  • Neoplasms / complications*
  • Neoplasms / diagnosis
  • Patient Selection
  • Pyridines / administration & dosage
  • Pyridines / adverse effects*
  • Recurrence
  • Risk Assessment
  • Risk Factors
  • Severity of Illness Index
  • Thiazoles / administration & dosage
  • Thiazoles / adverse effects*
  • Time Factors
  • Treatment Outcome
  • Venous Thromboembolism / diagnosis
  • Venous Thromboembolism / drug therapy*
  • Venous Thromboembolism / etiology

Substances

  • Anticoagulants
  • Factor Xa Inhibitors
  • Pyridines
  • Thiazoles
  • edoxaban
  • Dalteparin