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

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.