The Risk of Recurrent Venous Thromboembolism After Discontinuing Anticoagulation in Patients with Acute Proximal DVT or PE
Prandoni P, Noventa F, Ghirarduzzi A, Pengo V, Bernardi E, Pesavento R, Iotti M, Tormene D, Simioni P, Pagnan A. 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. Haematologica 2007; 92:199-205.
ABSTRACT: 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.
Discontinuing Anticoagulation Therapy in Patients with Venous Thromboembolism: A Risky Proposition
Review by Ranjith Shetty, MD
Up to 25% of patients with symptomatic deep vein thrombosis (DVT) or pulmonary embolism (PE) will have recurrent venous thromboembolism (VTE) within 5 years after their initial diagnosis. It is well established that patients with venous thromboembolic events that are of unknown origin or idiopathic have a much higher rate of recurrent VTE than patients with VTE following surgery or trauma. What is not well established is which other risk factors predispose patients to recurrent VTE. In this prospective cohort study, consecutive patients with proximal DVT and/or PE received anticoagulation therapy with warfarin for 3 months if VTE was provoked or at least 6 months if VTE was idiopathic. Enrollment in the study took place on the day of warfarin discontinuation, and patients were followed for a maximum of 10 years. Patients were excluded if they had a history of previous, symptomatic VTE, active cancer, required indefinite duration anticoagulation for other medical conditions, or had a life expectancy < 6 months. The goal of the study was to identify clinical parameters associated with a higher likelihood of recurrence in both the entire cohort and, separately, in patients with idiopathic VTE.
Patients were classified as having secondary or provoked VTE if they were pregnant, had given birth within the last 3 months, took estrogens, recent (less than 3 months) leg trauma, fracture, or surgical intervention, or bedridden for more than 1 week because of a chronic medical illness. All other patients were considered to have an idiopathic VTE.
1,626 patients completed the initial period of anticoagulation and were enrolled. 373 (22.9%) experienced recurrent VTE. 43 (11.5%) of all recurrences were either documented fatal PE or sudden and otherwise inexplicable deaths, in which PE could not be ruled out. Cumulative incidence of recurrent VTE at 10 years was reported as 39.9% (95% CI, 35.4 to 44.4).
Among patients with provoked VTE, those with medical diseases were more likely to develop recurrent thromboembolism than those with recent trauma or surgery (31.8% versus 11.4 %). Patients with idiopathic thrombosis were more than twice as likely to have a recurrent VTE than those who had a provoked DVT (52.6% versus 22.5%). Thrombophilia was found to be an independent risk factor in the entire cohort and in the subgroup of patients with unprovoked VTE. Patients with DVT had a 50% higher risk of recurrence than patients with PE. Patients with clinically manifested PE, however, were more likely to develop a recurrent PE than patient with DVT alone (57% versus 24%). Shorter courses of anticoagulation were also associated with significantly higher rates of recurrence than were longer periods of anticoagulation. Men and women had a similar risk of recurrence.
As expected, the study identified those patients with idiopathic VTE as being high risk for recurrence. Independently, however, patients with increasing age, thrombophilia, prolonged immobility due to medical disease, a presenting diagnosis of DVT, and shorter duration of anticoagulation were also at higher risk for recurrence. More studies need to be done to verify these clinical features as risk factors for recurrent VTE, but they deserve consideration when deciding when to discontinue anticoagulation therapy.About Ranjith Shetty, MD: Dr. Shetty completed his internship and residency in internal medicine at Georgetown University. During his year as a Venous Thromboembolism Research Fellow, he was currently involved with investigator initiated and multi-center trials at Brigham and Women’s hospital looking at novel anticoagulant treatment strategies for venous thromboembolism. Currently, Dr. Shetty is a first year Cardiology Fellow at the Medical College of Virginia in Richmond, VA.