Clinical Decision Rule Validation Study to Predict Low Recurrent Risk in Patients With Unprovoked Venous Thromboembolism

Up to 50% of patients with a first episode of venous thromboembolism (VTE) have no
identifiable cause (i.e. are unprovoked VTEs). The risk of recurrent VTE in this large group
of patients with unprovoked VTE after 3-6 months of anticoagulant therapy is 5-10.8% in the
year following discontinuation of oral anticoagulant therapy. One in six to one in twenty
recurrences of a new VTE are fatal. Given the intermediate risks of recurrence in unselected
unprovoked VTE patients, clinicians do not have clear guidance on whether to continue or
discontinue anticoagulants in patients with unprovoked VTE. Recently attention has turned to
the concept of risk stratification to identify subgroups of patients with unprovoked VTE who
could safely discontinue oral anticoagulation therapy (OAT).

In the REVERSE I study, a clinical decision rule derivation study conducted from 2001 to
2006, we developed and internally validated the clinical decision rule "Men continue and HER
DOO2" that identifies patients with a first unprovoked VTE who likely have a low risk of
recurrent VTE and could safely discontinue OAT subsequent to 5-7 months of OAT. The present
study will evaluate if the "Men continue and HER DOO2" rule (comprised of gender, elevated
D-dimer levels, post-thrombotic signs, obesity, and older age) is safe, clinically useful,
and reproducible when prospectively implemented in multiple centers and a variety of
settings. If this clinical decision rule is validated, it will provide physicians with
important information to allow them to more confidently identify unprovoked VTE patients at
low risk of VTE recurrence who may not need to continue OAT.

Inclusion Criteria:

- First episode of major unprovoked VTE

- VTE objectively proven

- VTE treated for 5-12 months with anticoagulant therapy authorized for the REVERSE II
study (initial or ongoing therapy)

- Absence of recurrent VTE during the treatment period

Exclusion Criteria:

- Less than 18 years of age

- Patients who have already discontinued anticoagulant therapy

- Patients requiring ongoing anticoagulation for reasons other than VTE

- Being treated for a recurrent unprovoked VTE

- Patients with high risk thrombophilia

- patients who plan on using exogenous estrogen(OCP,HRT)if anticoagulant therapy is
discontinued

- Patients with pregnancy associated VTE

- Geographically inaccessible for follow-up

- Patients unable or unwilling to provide informed consent