Systematic review: case-fatality rates of recurrent venous thromboembolism and major bleeding events among patients treated for venous thromboembolism

Ann Intern Med. 2010 May 4;152(9):578-89. doi: 10.7326/0003-4819-152-9-201005040-00008.


Background: Case-fatality rates are important for assessing the risks and benefits of anticoagulation in patients with venous thromboembolism (VTE).

Purpose: To summarize case-fatality rates of recurrent VTE and major bleeding events during anticoagulation and recurrent VTE after anticoagulation.

Data sources: MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, and all evidence-based medicine reviews in the Ovid interface through the second quarter of 2008.

Study selection: 69 articles (13 prospective cohort studies and 56 randomized, controlled trials) that reported on patients with symptomatic VTE who received anticoagulation therapy for at least 3 months and on the rate of fatal recurrent VTE and fatal major bleeding.

Data extraction: Two reviewers independently extracted data onto standardized forms.

Data synthesis: During the initial 3 months of anticoagulation, the rate of recurrent fatal VTE was 0.4% (95% CI, 0.3% to 0.6%), with a case-fatality rate of 11.3% (CI, 8.0% to 15.2%). The rate of fatal major bleeding events was 0.2% (CI, 0.1% to 0.3%), with a case-fatality rate of 11.3% (CI, 7.5% to 15.9%). After anticoagulation, the rate of fatal recurrent VTE was 0.3 per 100 patient-years (CI, 0.1% to 0.4%), with a case-fatality rate of 3.6% (CI, 1.9% to 5.7%).

Limitations: Estimates come from heterogeneous trial and cohort populations and are not derived from patient-level longitudinal data. Differences in case-fatality rates during and after anticoagulation may be attributable to unmeasured patient characteristics.

Conclusion: The case-fatality rates of recurrent VTE and major bleeding events are similar during the initial period of VTE treatment. The case-fatality rate of recurrent VTE decreases after completion of the initial period of anticoagulation. When combined with absolute rates of recurrent VTE and major bleeding events, case-fatality rates provide clinicians with a surrogate measure of mortality to balance the risks and benefits of anticoagulant therapy in patients with VTE.

Primary funding source: Canadian Institute for Health Research and Heart and Stroke Foundation of Ontario.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Anticoagulants / adverse effects*
  • Hemorrhage / chemically induced*
  • Hemorrhage / mortality
  • Humans
  • Recurrence
  • Risk Assessment
  • Venous Thromboembolism / drug therapy*
  • Venous Thromboembolism / mortality*


  • Anticoagulants