Comparison of Oral Anticoagulants for Extended VEnous Thromboembolism

Determine if apixaban is superior to warfarin in the reduction of clinically relevant
bleeding. Determine if rivaroxaban is superior to warfarin in the reduction of clinically
relevant bleeding. Determine if apixaban is non-inferior to warfarin in the prevention of
recurrent venous thromboembolism. Determine if rivaroxaban is non-inferior to warfarin in the
prevention of recurrent venous thromboembolism. An exploratory comparison of apixaban versus
rivaroxaban for the prevention of clinically relevant bleeding and recurrent Venous
Thromboembolism (VTEs) as a secondary objective.

3.1 Inclusion Criteria

To be eligible for this trial, patients must meet all of the following criteria:

- Have confirmed acute, symptomatic, first lower extremity proximal DVT and/or PE that
is NOT associated with a transient risk factor.

- Have completed an initial treatment course of oral anticoagulant therapy for 3-12
months and have a recommendation from their provider to continue anticoagulation
indefinitely.

- Have the capacity to understand and sign an informed consent form.

- Be 18 years of age and older.

- Under the direct care of a healthcare provider for treatment of VTE for the length of
time in the study.

3.2 Exclusion Criteria

If a patient meets any of the following criteria, he or she may not be enrolled in the
study:

- Creatinine clearance (CrCl) < 30 mL/min as determined by Cockcroft-Gault formula
documented within 3 months from date of consent

- Significant liver disease (Child-Pugh B or C)

- Concomitant use of medications that are strong P-glycoprotein or CYP3A4
inducers/inhibitors

- Another indication for chronic therapeutic-dose anticoagulation, such as atrial
fibrillation (i.e., rivaroxaban, 10 mg daily, or apixaban, 2.5 mg twice daily, would
not be appropriate therapy)

- A clinical indication for a specific anticoagulant regimen (e.g., warfarin with a
target INR of 2-3 is recommended for patients with 'triple-positive' antiphospholipid
syndrome).

- Life expectancy < 3 months

- Currently pregnant or breast feeding

- Unable / unwilling to pay for one (or more) of the treatment options

- Active Cancer defined as:

Diagnosed with cancer within the past 6 months; or Recurrent, regionally advanced or
metastatic disease; Currently receiving treatment or have received any treatment for cancer
during the 6 months prior to randomization; or A hematologic malignancy not in complete
remission

• Unwilling / unlikely to agree to follow up