Long-term risk of recurrence in patients with a first unprovoked venous thromboembolism managed according to d-dimer results; A cohort study

J Thromb Haemost. 2019 Jul;17(7):1144-1152. doi: 10.1111/jth.14458. Epub 2019 May 20.

Abstract

Essentials Long-term recurrence risk after a first unprovoked VTE with negative d-dimer levels is uncertain. Anticoagulation was stopped if d-dimer was negative, and was continued if d-dimer was positive. Five years after stopping anticoagulants, recurrent VTE was 30% in men and 17% in women. Negative d-dimers do not justify stopping anticoagulants in most men but appear to in most women.

Background: The long-term risk of recurrence in patients with a first unprovoked venous thromboembolism (VTE) who have negative d-dimer results is uncertain.

Objectives: To determine this risk, including in subgroups based on sex.

Patients and methods: ln a prospective interventional cohort study of 410 patients with a first unprovoked VTE, anticoagulants were stopped if d-dimer was negative on therapy and 1 month after stopping therapy. Other patients remained on anticoagulant therapy. We previously reported findings after a mean of 2.2 years. The current report includes 3 years of additional follow-up in 293 of these patients.

Results: During a median follow-up of 5.0 years, recurrent VTE after stopping therapy in response to negative d-dimer testing was 5.1% (95% confidence interval [CI], 3.6-6.5) per patient-year overall, 7.5% (95% CI, 5.5-10.0) in men, 3.8% (95% CI, 2.0-6.6) in women with VTE not associated with estrogens, and 0.4% (95% CI, 0.0-2.3) in women with VTE associated with estrogens (P < 0.001 for three-group comparison). Risk of recurrence at 5 years was 21.5% (95% CI, 16.4-26.5) overall, 29.7% (95% CI, 22.1-37.3) in men, 17.0% (95% CI, 8.1-25.9) in non-estrogen women, and 2.3% (95% CI, 0.0-6.8) in estrogen women.

Conclusion: The long-term risk of recurrence in patients with a first unprovoked VTE who have negative d-dimer results is not low enough to justify stopping anticoagulant therapy in men, but appears to be low enough in women for many to choose stopping therapy (ClinicalTrials.gov; NCT00720915).

Keywords: cohort study; d-dimer; deep vein thrombosis; extended follow-up; pulmonary embolism; treatment; venous thromboembolism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Anticoagulants / administration & dosage*
  • Biomarkers / blood
  • Clinical Decision-Making
  • Drug Administration Schedule
  • Female
  • Fibrin Fibrinogen Degradation Products / analysis*
  • Humans
  • Male
  • Middle Aged
  • Predictive Value of Tests
  • Prospective Studies
  • Recurrence
  • Risk Assessment
  • Risk Factors
  • Sex Factors
  • Time Factors
  • Treatment Outcome
  • Venous Thromboembolism / blood
  • Venous Thromboembolism / diagnosis
  • Venous Thromboembolism / drug therapy*

Substances

  • Anticoagulants
  • Biomarkers
  • Fibrin Fibrinogen Degradation Products
  • fibrin fragment D

Associated data

  • ClinicalTrials.gov/NCT00720915