Patients who have experienced an unprovoked pulmonary embolism (PE) may experience recurrence after stopping anticoagulant therapy, but the optimal duration of anticoagulation treatment is unclear. The primary objective of the double-blind multicenter PADIS-PE study [Couturaud F et al. JAMA. 2015] was to evaluate the efficacy and safety of an additional 18 months of oral anticoagulant treatment following an initial 6 months of therapy. The ability to classify patients according to risk of recurrence is also of benefit given the risks associated with anticoagulation therapy. Another objective of the study was to identify such risk factors. Findings from the study were presented by Francis Couturaud, MD, PhD, European Brittany University, Brest, France.

In the PADIS-PE study, 371 patients with their first unprovoked PE received 6 months of vitamin K antagonist treatment and were randomized to an additional 18 months of warfarin treatment (n = 184) or placebo (n = 187). At randomization, blood samples were taken, and patients underwent a ventilation/perfusion (V/Q) lung scan, echocardiography, and compression ultrasound of the legs. Patients were evaluated at the end of the 18-month treatment period and followed for an additional 2 years.

During 18 months of treatment, the primary outcome (composite of recurrent symptomatic venous thromboembolism [VTE] and major bleeding at 18 months) occurred in 3.3% of warfarin-treated patients vs 13.5% of placebo-treated patients (HR, 0.22; 95% CI, 0.09 to 0.55; P = .001). Recurrent symptomatic VTE occurred in 1.7% of warfarin-treated patients and 13.5% of those receiving placebo (HR, 0.11; 95% CI, 0.03 to 0.37; P < .0001). Major bleeds were not significantly different between the 2 groups (2.2% warfarin, 0.5% placebo; HR, 4.07; 95% CI, 0.45 to 36.38; P = .18). Over the entire study period, there were no statistically significant differences between the 2 treatment groups in composite events (20.8% warfarin vs 24.0% placebo; HR, 0.74; 95% CI, 0.47 to 1.17; P = .19), recurrent symptomatic VTE (17.9% warfarin vs 22.1% placebo; HR, 0.67; 95% CI, 0.41 to 1.08; P = .10), or major bleeds (3.5 warfarin vs 3.0 placebo; HR, 1.12; 95% CI, 0.38 to 4.10; P = .71).

One of the secondary objectives was to determine risk factors for recurrent symptomatic VTE during the 42-month follow-up period. Symptomatic recurrent VTEs were defined as follows: nonfatal recurrent PE (clinical suspicion of PE with positive V/Q lung scan, spiral computed tomography angiography, pulmonary angiography, or new noncompressibility of a proximal vein on ultrasound), fatal recurrent VTE (autopsy or unexplained sudden death), and symptomatic recurrent deep vein thrombosis (DVT; clinical suspicion of DVT and noncompressibility of a new segment of a proximal vein on ultrasound). Univariate analysis and a multivariate model were used to identify risk factors for recurrent VTE.

Age, residual perfusion defect at study inclusion, and residual DVT at study inclusion were identified as independent risk factors associated with recurrent VTE based on multivariate analysis (Table 1). On the basis of these findings, Dr Couturaud noted that it may be useful to perform a V/Q lung scan and lower limb ultrasound after 6 months of anticoagulation to help determine a patient’s risk of recurrent VTE if treatment is discontinued.