Thromb Haemost 2017; 117(10): 1944-1951
DOI: 10.1160/TH16-12-0946
Stroke, Systemic or Venous Thromboembolism
Schattauer GmbH

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
Suzanne M. Bleker*
1  Department of Vascular Medicine, Academic Medical Center, Amsterdam, the Netherlands
,
Marjolein P.A. Brekelmans*
1  Department of Vascular Medicine, Academic Medical Center, Amsterdam, the Netherlands
,
Elise S. Eerenberg
1  Department of Vascular Medicine, Academic Medical Center, Amsterdam, the Netherlands
,
Alexander T. Cohen
2  Department of Haematological Medicine, Guy’s and St Thomas’ Hospitals, King’s College London, London, UK
,
Saskia Middeldorp
1  Department of Vascular Medicine, Academic Medical Center, Amsterdam, the Netherlands
,
Gary Raskob
3  College of Public Health, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA
,
Harry R. Büller
1  Department of Vascular Medicine, Academic Medical Center, Amsterdam, the Netherlands
› Author Affiliations
Further Information

Publication History

Received: 19 December 2016

Accepted after major revision: 24 June 2017

Publication Date:
28 November 2017 (online)

Summary

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.

* Both authors contributed equally to this manuscript.