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.
© 2019 International Society on Thrombosis and Haemostasis.
D-dimer testing to select patients with a first unprovoked venous thromboembolism who can stop anticoagulant therapy: a cohort study.Ann Intern Med. 2015 Jan 6;162(1):27-34. doi: 10.7326/M14-1275. Ann Intern Med. 2015. PMID: 25560712 Clinical Trial.
Patient-level meta-analysis: effect of measurement timing, threshold, and patient age on ability of D-dimer testing to assess recurrence risk after unprovoked venous thromboembolism.Ann Intern Med. 2010 Oct 19;153(8):523-31. doi: 10.7326/0003-4819-153-8-201010190-00009. Ann Intern Med. 2010. PMID: 20956709 Review.
Systematic review: D-dimer to predict recurrent disease after stopping anticoagulant therapy for unprovoked venous thromboembolism.Ann Intern Med. 2008 Oct 7;149(7):481-90, W94. doi: 10.7326/0003-4819-149-7-200810070-00008. Ann Intern Med. 2008. PMID: 18838728 Review.
Long term risk of symptomatic recurrent venous thromboembolism after discontinuation of anticoagulant treatment for first unprovoked venous thromboembolism event: systematic review and meta-analysis.BMJ. 2019 Jul 24;366:l4363. doi: 10.1136/bmj.l4363. BMJ. 2019. PMID: 31340984 Free PMC article.
The long-term recurrence risk of patients with unprovoked venous thromboembolism: an observational cohort study.J Thromb Haemost. 2016 Dec;14(12):2402-2409. doi: 10.1111/jth.13524. Epub 2016 Nov 19. J Thromb Haemost. 2016. PMID: 27696701 Clinical Trial.
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