Clinical Impact of Bleeding in Patients Taking Oral Anticoagulant Therapy for Venous Thromboembolism

Clinical Impact of Bleeding in Patients Taking Oral Anticoagulant Therapy for Venous Thromboembolism

A Meta-Analysis

Lori-Ann Linkins, MD, FRCP(C);
Peter T. Choi, MD, MSc, FRCP(C); and
James D. Douketis, MD, FRCP(C)

From McMaster University, Hamilton, Ontario, Canada; and University of British Columbia, Vancouver, British Columbia, Canada.

Abstract

Background: Clinicians should consider the clinical impact of anticoagulant-related bleeding when deciding on the duration of anticoagulant therapy in patients with venous thromboembolism.

Purpose: To provide reliable estimates of the clinical impact of anticoagulant-related bleeding, defined as the case-fatality rate of major bleeding and the risk for intracranial bleeding.

Data Sources: MEDLINE (January 1989 to May 2003), Cochrane Controlled Trial Registry, thromboembolism experts, and reference lists; English-language literature only.

Study Selection: Randomized, controlled trials and prospective cohort studies that investigated patients with venous thromboembolism who received oral anticoagulant therapy (target international normalized ratio, 2.0 to 3.0) for at least 3 months and that reported major bleeding and death as primary study outcomes.

Data Extraction: Two reviewers independently extracted data on the number of anticoagulant-related major and intracranial bleeding episodes and on whether these events were fatal or nonfatal.

Data Synthesis: The authors analyzed 33 studies involving 4374 patient-years of oral anticoagulant therapy. For all patients, the case-fatality rate of major bleeding was 13.4% (95% CI, 9.4% to 17.4%) and the rate of intracranial bleeding was 1.15 per 100 patient-years (CI, 1.14 to 1.16 per 100 patient-years). For patients who received anticoagulant therapy for more than 3 months, the case-fatality rate of major bleeding was 9.1% (CI, 2.5% to 21.7%), and the rate of intracranial bleeding was 0.65 per 100 patient-years (CI, 0.63 to 0.68 per 100 patient-years) after the initial 3 months of anticoagulation.

Conclusion: The clinical impact of anticoagulant-related major bleeding in patients with venous thromboembolism is considerable, and clinicians should take this into account when deciding whether to continue long-term oral anticoagulant therapy in an individual patient.

Article and Author Information

Acknowledgments: The authors thank Drs. Clive Kearon, Mark Crowther, Lehana Thabane, and Jack Hirsh for their helpful reviews of the manuscript.
Grant Support: Dr. Linkins is the recipient of a Fellowship Award from the Heart & Stroke Scientific Research Corporation of Canada/AstraZeneca Canada, Inc. Dr. Douketis is a recipient of a Research Scholarship from the Heart and Stroke Foundation of Canada.
Potential Financial Conflicts of Interest: None disclosed.
Requests for Single Reprints: James D. Douketis, MD, FRCP(C), St. Joseph's Healthcare, Room F-541, 50 Charlton Avenue East, Hamilton, Ontario L8N 4A6, Canada; e-mail, jdouket{at}mcmaster.ca.
Current Author Addresses: Dr. Linkins: Henderson Research Centre, Room 220, 711 Concession Street, Hamilton, Ontario L8V 1C3, Canada.
Dr. Choi: Department of Anesthesia, University of British Columbia, 2329 West Mall, Vancouver V6T 1Z4, British Columbia.
Dr. Douketis: St. Joseph's Healthcare, Room F-541, 50 Charlton Avenue East, Hamilton, Ontario L8N 4A6, Canada.
Author Contributions: Conception and design: L.A. Linkins, J.D. Douketis.
Analysis and interpretation of the data: L.A. Linkins, P.T. Choi, J.D. Douketis.
Drafting of the article: L.A. Linkins, J.D. Douketis.
Critical revision of the article for important intellectual content: L.A. Linkins, P.T. Choi, J.D. Douketis.
Final approval of the article: L.A. Linkins, P.T. Choi, J.D. Douketis.
Statistical expertise: P.T. Choi.
Administrative, technical, or logistic support: J.D. Douketis.
Collection and assembly of data: L.A. Linkins.