Patient Care

Extended Anticoagulation Therapy and Recurrent Rates of Venous Thromboembolism


Clinical question: Among patients with a first episode of unprovoked pulmonary embolism (PE), what are the benefits and harms of extending the duration of anticoagulation for secondary prophylaxis against recurrent VTE?

Background: Optimal duration of anticoagulation after initial unprovoked PE is not known. Prior studies demonstrated risk reduction of recurrent VTE while on therapy but have had inadequate long-term monitoring of patients or enrollment of patients with PE, who are known to have a higher case-fatality rate of recurrent VTE than patients with DVT.

Study design: Multicenter, randomized, double-blinded, parallel-grouped, placebo-controlled trial.

Setting: Fourteen French hospitals from 2007 to 2012.

Synopsis: Investigators randomized 371 patients with a first episode of symptomatic unprovoked PE who had completed six months of warfarin to 18 additional months of warfarin or placebo. Patients were followed for 24 months after discontinuation of therapy.

During the treatment period, the primary outcome (composite of recurrent VTE and major bleeding) occurred in 3.3% of the warfarin group vs. 13.5% of the placebo group (HR 0.22). This difference was primarily due to reduction in risk of recurrent VTE (1.7% vs. 13.5%, HR 0.15), with only minimal increased bleeding risk (2.2% vs. 0.5%, NS).

There was no significant difference in the composite outcome (20.8% in warfarin group vs. 24% in placebo) on analysis of the entire study period (treatment and follow-up), however, suggesting the benefit of extended warfarin therapy upon recurrent VTE risk diminished upon cessation.

Bottom line: Patients treated with extended-therapy warfarin after a first unprovoked PE have a decreased risk of recurrent VTE compared to standard therapy only while on treatment; the risk of recurrent VTE returns upon cessation of therapy.

Citation: Couturand F, Sanchez O, Pernod G, et al. Six months vs extended oral anticoagulation after a first episode of pulmonary embolism: The PADIS-PE randomized clinical trial. JAMA. 2015;314(1):31-40.

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