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Optimal Duration of Anticoagulation for Venous Thromboembolism

Using ultrasonography data to guide duration of therapy helped lower rates of recurrent VTE.

After a first episode of deep venous thrombosis (DVT), most patients receive anticoagulation therapy with warfarin for 3 to 6 months. However, thrombi can recur after therapy is discontinued. Although ongoing anticoagulation can forestall recurrence, the longer the duration of therapy, the higher the risk for major bleeding. To provide guidance in selecting the optimal duration of anticoagulation therapy, investigators conducted a randomized, multicenter trial involving 538 Italian outpatients with first-proximal DVT to assess whether serial duplex ultrasonography (US) can facilitate treatment decisions.

After receiving anticoagulation therapy for 3 months, patients were randomized to fixed-duration or US-guided (flexible-duration) warfarin therapy. In the fixed-duration group, patients who had idiopathic DVT received an additional 3 months of therapy, and patients who experienced provoked DVT (i.e., after surgery, trauma, prolonged immobilization, or hormonal therapy) discontinued therapy. In the US-guided group, therapy was continued if thrombi persisted and discontinued if veins had recanalized. US was repeated at 3, 9, 15, and 21 months after randomization in patients with idiopathic DVT and at 3 and 9 months in those with provoked DVT.

Overall, after 33 months, fewer patients in the US-guided group (32 of 270 [12%]) than in the fixed-duration group (46 of 268 [17%]) experienced recurrent venous thromboembolism (VTE; hazard ratio, 0.64; 95% confidence interval, 0.39–0.99). Similarly, among patients with idiopathic DVT, fewer in the US-guided group (24 of 155 [15%]) than in the fixed-duration group (36 of 151 [24%]) had recurrent VTE (HR, 0.61; 95% CI, 0.36–1.02); however, among those with provoked DVT, the HR for this comparison was not significant (see chart). Among all patients, fewer in the US-guided group than in the fixed-duration group had residual thrombi (54 of 270 [20%] vs. 79 of 268 [29%]; P=0.02). Bleeding complications were rare in both groups.

Comment: Patients and physicians are often disappointed by the slow and incomplete recanalization of proximal DVT. These findings show that, despite continuing anticoagulation for as long as 2 years, 20% of patients still had residual thrombi and that longer-term anticoagulation had only a modest effect on preventing recurrent VTE. Nevertheless, the study demonstrates that US can assist in decision making about the duration of anticoagulation; moreover, US can complement clinical examination and D-dimer testing in helping to determine treatment length.

— David Green, MD, PhD

Published in Journal Watch Oncology and Hematology May 19, 2009

Citation(s):

Prandoni P et al. Residual thrombosis on ultrasonography to guide the duration of anticoagulation in patients with deep venous thrombosis: A randomized trial. Ann Intern Med 2009 May 5; 150:577.

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