Incidence of Recurrent Venous Thromboembolism According to Duration of Vitamin K Antagonists: Results of a Meta-Analysis on Individual Data.

Objective: 1) to describe the incidence of recurrent venous thromboembolism (VTE) after stopping treatment with vitamin K antagonists (VKA); 2) to determine if the incidence of recurrent VTE is influenced by the duration of VKA therapy.

Methods: We performed a meta-analysis on the individual data of patients included in five randomized controlled trials (ODAC, DURAC 1, LAFIT, WODIT DVT, DOTAVK studies) that assessed several durations of oral treatment with VKA after an episode of VTE. A Poisson linear regression model was used to estimate the rate of recurrent VTE over time in patients off treatment with VKA, according to the duration of treatment (1.5, 3, 6 and ≥12 months).

Results: 2365 patients were followed for an average of 24.5 months after stopping therapy, and 330 recurrent VTE were observed. Estimation of the hazard functions in patients off treatment revealed that the rate of recurrent VTE decreased rapidly over the first year following the index event, independently of the duration of treatment with VKA, and stabilized afterwards. In addition, a peak of recurrences was observed in the first 1 to 3 months after stopping therapy, in all treatment duration groups. The rate of recurrent VTE after the short-term peak did not seem to be modified by the duration of therapy, after accounting for the time elapsed since the index event.

Discussion: After a treated episode of VTE, the rate of recurrence declined exponentially over time. This result may be explained by 1) the natural evolution of recurrence rate after an acute VTE; 2) the heterogeneity of recurrence rate among patients (with higher risk patients experiencing recurrences sooner than lower risk patients). The peak of recurrent VTE observed in the first 1 to 3 months after stopping treatment regardless of the duration of anticoagulant therapy may suggest that some patients are exposed to a very high risk of recurrence as soon as the protective effect of treatment is released.