This vanguard pilot study compares rivaroxaban and apixaban, two of the new oral blood thinners for the treatment of blood clots. Half of the patients will receive apixaban and half will receive rivaroxaban. The main objective is to determine the feasibility of patient recruitment and resources required to follow enrolled patients and inform for a larger, multi-centered trial and to assess which one is safer.

Recently developed new oral anticoagulants (OAC) overcome some of the limitations of established therapy with vitamin K antagonists (VKA) and low molecular weight heparin (LMWH) for treatment of acute venous thromboembolism (VTE), due to ease of administration and more predictable pharmacokinetic properties. Many clinical questions about the new OAC remain unanswered because there have not been direct head-to-head comparison trials. For example, although studies have shown that rivaroxaban and apixaban are at least as effective and safe as LMWH and VKA, meta-analyses suggest that apixaban may be associated with lower bleeding risk. Concerns about the potential impact of medication non-adherence have been raised. Compliance with twice daily medications (e.g. apixaban) is often worse than once daily medications (e.g. rivaroxaban). Both of these medications are approved by Health Canada for treatment of VTE yet there is genuine uncertainty about which of the two direct OAC confer the best risk-to-benefit ratio.This is a multi-centre, prospective randomized open blinded end-point (PROBE) trial assessing clinical feasibility for a larger multi-centered trial comparing bleeding outcomes using apixaban vs. rivaroxaban for treatment of acute VTE. The primary objective of the study is to determine if it is feasible to conduct a large randomized multicenter trial comparing apixaban vs. rivaroxaban for the treatment of acute VTE. The secondary objectives are to assess safety and superiority of apixaban vs rivaroxaban.

Inclusion Criteria:

• Confirmed newly diagnosed acute VTE (proximal lower extremity deep vein thrombosis and segmental or greater pulmonary embolism)
• Age ≥ 18 years old
• Written informed consent

Exclusion Criteria:

• Any contraindication for anticoagulation such as active bleeding
• Clinically significant liver disease or alanine aminotransferase (ALT) levels ≥ 3 times the upper limit of normal range
• Creatinine clearance < 30 ml/min calculated with the Cockcroft-Gault formula (29)
• Known allergies to either apixaban or rivaroxaban
• Pregnancy
• Use of contraindicated medications with apixaban or rivaroxaban
• Active malignancy in the last 6 months (excluding localized skin malignancy)
• No private insurance coverage for the study drug or not willing to pay for study drug