Flexible duration anticoagulation guided by ultrasonography reduced recurrent VTE

Researchers tailored the duration of anticoagulation based on the persistence of residual thrombi on ultrasonography results.

Using the results of ultrasonography to determine the optimal duration of anticoagulation therapy among adults with proximal deep venous thrombosis reduced the rate of recurrent venous thromboembolism, according to data from a parallel, randomized trial published in Annals of Internal Medicine.

“At the moment, we have either been giving patients a fixed duration of anticoagulation if they have a provoked VTE or an indefinite duration of anticoagulation, which is sometimes lifelong anticoagulation, if they have an unprovoked and idiopathic DVT or pulmonary embolism,” Samuel Z. Goldhaber, MD, director of the Venous Thromboembolism Research Group, Brigham and Women’s Hospital, told HemOnc Today.

In an accompanying editorial, Goldhaber explained that a conflict exists between a population-based approach to anticoagulation duration and an individualized strategy. Researchers from Italy aimed to explore both sides of the debate to determine whether an individualized approach using ultrasonography to guide anticoagulation dosing could reduce the rate of recurrent VTE.

The study included 538 patients who experienced first acute proximal DVT after completing three months of anticoagulation. Patients were randomly assigned to fixed-duration (n=268) or flexible-duration (n=270) anticoagulation. Fixed-duration treatment was defined as no further anticoagulation for secondary thrombosis and an additional three months for unprovoked thrombosis. Flexible-duration treatment was defined as no further anticoagulation in patients with recanalized veins and continued therapy for up to nine months for secondary DVT and up to 21 months for unprovoked thrombosis.

Follow-up was completed in 538 patients, 78 of whom developed recurrent thromboembolism. Of the 78 events, 17.2% occurred in patients assigned to fixed-duration and 11.9% of those assigned to flexible-duration (HR=0.64; 95% CI, 0.39-0.99). The HR for recurrent VTE in patients with unprovoked DVT was 0.61 (95% CI, 0.36-1.02); for those with secondary DVT the HR was 0.81 (95% CI, 0.32-2.06). Over time, patients assigned to flexible-duration treatment had a lower rate of recurrent DVT compared with those assigned to fixed-duration (see chart).

In the fixed-duration arm, two patients with unprovoked DVT experienced a major bleeding event compared with four patients with secondary DVT and unprovoked thrombosis in the flexible-duration arm. Death occurred among 11 patients assigned to fixed-duration and 17 assigned to flexible-duration (P=.33).

“The main shortcoming of the trial is its somewhat limited applicability to standard practice,” Goldhaber wrote in his editorial. “The anticoagulation regimen for the fixed-duration group was far shorter than most practitioners prescribe.”

The researchers listed additional limitations to their study, including the exclusion of patients with previous thromboembolism, permanent risk factor for thrombosis and thrombophilic abnormalities other than Factor V leiden and prothrombin mutation. According to Goldhaber, such exclusions limit the applicability of the findings. In addition, the researchers did not compare thrombosis with other risk factors as predictors of recurrence after discontinuing anticoagulation.

“These data raise the possibility that some patients should not be assigned to either fixed or indefinite duration anticoagulation,” he said. “But there may be a role for flexible doses in some patients which would be an intermediate approach between the two current conventional approaches.”

To end his editorial, Goldhaber states that the most sensible approach is to follow current guidelines for the duration of anticoagulation, which recommend time-limited doses for provoked VTE and indefinite for idiopathic VTE. – by Stacey L. Adams

Goldhaber. Ann Intern Med. 2009;150:644-646.

Prandoni. Ann Intern Med. 2009;150:577-585.