The risk of recurrent venous thromboembolism after discontinuing anticoagulation in patients with acute proximal deep vein thrombosis or pulmonary embolism. A prospective cohort study in 1,626 patients

Background and Objectives While it has long been recognized that patients with acute unprovoked deep vein thrombosis (DVT) or pulmonary embolism (PE) have a higher risk of recurrent venous thromboembolism (VTE) than that of patients with secondary thrombosis, whether other clinical parameters can help predict the development of recurrent events is controversial. The aim of this investigation was to assess the rate of recurrent VTE after withdrawal of vitamin K antagonists, and to identify clinical parameters associated with a higher likelihood of recurrence. Design and Methods We followed, up to a maximum of 10 years, 1626 consecutive patients who had discontinued anticoagulation after a first episode of clinically symptomatic proximal DVT and/or PE. All patients with clinically suspected recurrent VTE underwent objective tests to confirm or rule out the clinical suspicion. Results After a median follow-up of 50 months, 373 patients (22.9%) had had recurrent episodes of VTE. The cumulative incidence of recurrent VTE was 11.0% (95% CI, 9.5-12.5) after 1 year, 19.6% (17.5-21.7) after 3 years, 29.1% (26.3-31.9) after 5 years, and 39.9% (35.4-44.4) after 10 years. The adjusted hazard ratio for recurrent VTE was 2.30 (95% CI, 1.82-2.90) in patients whose first VTE was unprovoked, 2.02 (1.52-2.69) in those with thrombophilia, 1.44 (1.03-2.03) in those presenting with primary DVT, 1.39 (1.08-1.80) for patients who received a shorter (up to 6 months) duration of anticoagulation, and 1.14 (1.06-1.12) for every 10-year increase of age. When the analysis was confined to patients with unprovoked VTE the results did not change. Interpretation and Conclusions Besides unprovoked presentation, other factors independently associated with a statistically significant increased risk of recurrent VTE are thrombophilia, clinical presentation with primary DVT, shorter duration of anticoagulation, and increasing age.