Clinical impact of bleeding in patients taking oral anticoagulant therapy for venous thromboembolism: a meta-analysis

Ann Intern Med. 2003 Dec 2;139(11):893-900. doi: 10.7326/0003-4819-139-11-200312020-00007.


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.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Anticoagulants / administration & dosage
  • Anticoagulants / adverse effects*
  • Drug Administration Schedule
  • Hemorrhage / chemically induced*
  • Humans
  • Intracranial Hemorrhages / chemically induced
  • Prospective Studies
  • Randomized Controlled Trials as Topic
  • Risk Factors
  • Thromboembolism / drug therapy*
  • Venous Thrombosis / drug therapy*


  • Anticoagulants