Clinical impact of major bleeding in patients with venous thromboembolism treated with factor Xa inhibitors or vitamin K antagonists. An individual patient data meta-analysis

Thromb Haemost. 2017 Oct 5;117(10):1944-1951. doi: 10.1160/TH16-12-0946. Epub 2017 Aug 17.

Abstract

Factor Xa (fXa)-inhibitors are as effective and safer than vitamin-K-antagonists (VKA) in the treatment of venous thromboembolism (VTE). We previously classified the severity of clinical presentation and course of all major bleeding events from the EINSTEIN, AMPLIFY and HOKUSAI-VTE trials separately. The current aim was to combine these findings in order to increase precision, assess a class effect and analyse presentation and course for different types of bleeding, i. e. intracranial, gastro-intestinal, and other. We classified the clinical presentation and course of all major bleeding events using pre-defined criteria. Both classifications comprised four categories; one being the mildest, and four the most severe. Odds ratios (OR) were calculated for all events classified as category three or four between fXa-inhibitors and VKA recipients. Also, ORs were computed for different types of bleeding. Major bleeding occurred in 111 fXa-inhibitor recipients and in 187 LMWH/VKA recipients. The clinical presentation was classified as category three or four in 35 % and 48 % of the major bleeds in fXa inhibitor and VKA recipients, respectively (OR 0.59, 95 % CI 0.36-0.97). For intracranial, gastro-intestinal and other bleeding a trend towards a less severe presentation was observed for patients treated with fXa inhibitors. Clinical course was classified as severe in 22 % of the fXa inhibitor and 25 % of the VKA associated bleeds (OR 0.83, 95 % CI 0.47-1.46). In conclusion, FXa inhibitor associated major bleeding events had a significantly less severe presentation and a similar course compared to VKA. This finding was consistent for different types of bleeding.

Keywords: Major bleeding; factor Xa inhibitors; vitamin K antagonists; venous thromboembolism.

Publication types

  • Meta-Analysis

MeSH terms

  • Aged
  • Aged, 80 and over
  • Anticoagulants / administration & dosage
  • Anticoagulants / adverse effects*
  • Blood Transfusion
  • Chi-Square Distribution
  • Factor Xa Inhibitors / administration & dosage
  • Factor Xa Inhibitors / adverse effects*
  • Female
  • Gastrointestinal Hemorrhage / chemically induced
  • Hemorrhage / chemically induced*
  • Hemorrhage / diagnosis
  • Hemorrhage / mortality
  • Hemorrhage / therapy
  • Humans
  • Intracranial Hemorrhages / chemically induced
  • Logistic Models
  • Male
  • Middle Aged
  • Odds Ratio
  • Randomized Controlled Trials as Topic
  • Risk Assessment
  • Risk Factors
  • Time Factors
  • Treatment Outcome
  • Venous Thromboembolism / blood
  • Venous Thromboembolism / diagnosis
  • Venous Thromboembolism / drug therapy*
  • Venous Thromboembolism / mortality
  • Vitamin K / antagonists & inhibitors*

Substances

  • Anticoagulants
  • Factor Xa Inhibitors
  • Vitamin K