Identifying unprovoked thromboembolism patients at low risk for recurrence who can discontinue anticoagulant therapy

Abstract

Background: Whether to continue oral anticoagulant therapy beyond 6 months after an "unprovoked" venous thromboembolism is controversial. We sought to determine clinical predictors to identify patients who are at low risk of recurrent venous thromboembolism who could safely discontinue oral anticoagulants.

Methods: In a multicentre prospective cohort study, 646 participants with a first, unprovoked major venous thromboembolism were enrolled over a 4-year period. Of these, 600 participants completed a mean 18-month follow-up in September 2006. We collected data for 69 potential predictors of recurrent venous thromboembolism while patients were taking oral anticoagulation therapy (5-7 months after initiation). During follow-up after discontinuing oral anticoagulation therapy, all episodes of suspected recurrent venous thromboembolism were independently adjudicated. We performed a multivariable analysis of predictor variables (p < 0.10) with high interobserver reliability to derive a clinical decision rule.

Results: We identified 91 confirmed episodes of recurrent venous thromboembolism during follow-up after discontinuing oral anticoagulation therapy (annual risk 9.3%, 95% CI 7.7%-11.3%). Men had a 13.7% (95% CI 10.8%-17.0%) annual risk. There was no combination of clinical predictors that satisfied our criteria for identifying a low-risk subgroup of men. Fifty-two percent of women had 0 or 1 of the following characteristics: hyperpigmentation, edema or redness of either leg; D-dimer > or = 250 microg/L while taking warfarin; body mass index > or = 30 kg/m(2); or age > or = 65 years. These women had an annual risk of 1.6% (95% CI 0.3%-4.6%). Women who had 2 or more of these findings had an annual risk of 14.1% (95% CI 10.9%-17.3%).

Interpretation: Women with 0 or 1 risk factor may safely discontinue oral anticoagulant therapy after 6 months of therapy following a first unprovoked venous thromboembolism. This criterion does not apply to men.

Trial registration: ClinicalTrials.gov NCT00261014.

Figures

Figure 1: Flow of participants through the study.

Figure 2: Potential predictor variables for men at optimal cutoff points, by strength of association. *Determined by χ2 testing, unless stated otherwise. †Presence of antiphospholipid (APL) antibodies was determined by anticardiolipin antibody (IgG or IgM) ≥ 6 U/mL or by a positive result for lupus anticoagulant. ‡Determined by the Fisher exact test. Note: BMI = body mass index, CI = confidence interval, HER = hyperpigmentation, edema or redness, RR = relative risk, VTE = venous thromboembolism.

Figure 3: Potential predictor variables for women at optimal cut-off points, by strength of association. *Determined by χ2 testing, unless stated otherwise. †Presence of antiphospholipid (APL) antibodies was determined by anticardiolipin antibody (IgG or IgM) ≥ 4 U/mL or by a positive result for lupus anticoagulant. ‡Determined by the Fisher exact test. Note: BMI = body mass index, CI = confidence interval, HER = hyperpigmentation, edema or redness, HRT = hormone replacement therapy, OCP = oral contraceptive pills, RR = relative risk, VTE = venous thromboembolism.

Figure 4: Survival estimates and cumulative risk of recurrent venous thromboembolism (VTE) after discontinuing oral anticoagulant therapy after 5–7 months. Patients were classified as low or high risk according to the candidate diagnostic rules for men and women. We performed the survival analysis with updated data in June 2007 (mean follow-up 22.5 months). Note: CI = confidence interval.

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