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Duration of Oral Anticoagulation for Venous Thromboembolism

Using D-dimer tests to evaluate low-risk patients allows for anticoagulation duration to be adjusted on a case-by-case basis.

Recurrent venous thromboembolism (VTE) occurs in as many as 30% of patients who discontinue oral anticoagulant therapy. Many factors are associated with high risk for recurrence, including proximal (versus distal) vein thrombosis, male sex, and body-mass index >30 kg/m² (Pathophysiol Haemost Thromb 2005; 34:6). Although continuing oral anticoagulation lowers risk for VTE recurrence, long-term treatment with warfarin is inconvenient and is associated with an annual 1% to 3% risk for major bleeding. Identifying patients whose risk for recurrence is low, and whose anticoagulation therapy could be safely discontinued, is a priority. D-dimer is a cross-linked degradation product of fibrin, and its concentration increases in patients with acute VTE. Persistent high levels of D-dimer can indicate ongoing risk for thrombus formation.

Investigators conducted a multicenter prospective examination of 608 patients (age range, 18–85) who experienced first episodes of symptomatic unprovoked VTE during 2002 to 2005. Patients took oral anticoagulants for at least 3 months; then, treatment was discontinued. One month later, D-dimer tests (Clearview Simplify rapid whole-blood method) were performed. Patients with normal D-dimer levels did not resume anticoagulants (385 patients; Group 1); those with elevated levels were randomized either to resume anticoagulation therapy (103; Group 2) or to remain off anticoagulants (120; Group 3).

During an average follow-up of 1.4 years, recurrence rates were 6.2% in Group 1, 1.9% in Group 2, and 15% in Group 3. Among patients who discontinued anticoagulants (Group 1 and Group 3), the hazard ratio for thrombotic events in Group 3 (high D-dimer levels) was 2.49 compared with Group 1 (P=0.003). Furthermore, among patients with high D-dimer levels (Group 2 and Group 3), those who did not resume anticoagulants had an HR of 5.36 compared with those who did (P=0.007). The authors concluded that high D-dimer levels predict high risk for recurrent VTE, and such risk can be minimized by resuming anticoagulant therapy.

Comment: Current recommendations call for patients with first episodes of unprovoked, proximal-vein thrombosis to continue oral anticoagulants for at least 6 to 12 months (Chest 2004; 126:401S). However, an alternate strategy would be to discontinue anticoagulation after 3 to 6 months in low-risk patients — those without major risk factors, such as obesity, cancer, antiphospholipid antibody syndrome, or large residual thrombi. After an interval of 2 to 4 weeks without anticoagulants, D-dimer concentrations should be measured. Those with normal results can remain off anticoagulants, and those with elevated values can resume therapy and be retested annually. Although the safety and efficacy of this strategy require further evaluation, the results of this study support such an approach.

— David Green, MD, PhD

Published in Journal Watch Oncology and Hematology October 30, 2006

Citation(s):

Palareti G et al. D-Dimer testing to determine the duration of anticoagulation therapy. N Engl J Med 2006 Oct 26; 355:1780-9.

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