Comparison of bleeding risk between rivaroxaban and apixaban for the treatment of acute venous thromboembolism

Principal Investigator: Dr Lana Castellucci, Ottawa Hospital Research Institute

Local Investigator: Dr Marcel Émond (emergency physician)- Dr Benoît Côté (physician intensivist), CHU de Québec – Université Laval

Local research coordinator: Alexandra Nadeau

Granting agency: Canadian Institutes of Health Research – CIHR

The main objective is to compare the risk of bleeding between rivaroxaban and apixaban for the treatment of acute venous thromboembolism.

Venous thromboembolism (VTE) is the third leading cause of death from cardiovascular disease. Standard treatment for acute VTE uses a combination of low molecular weight heparin and oral vitamin K antagonists for 3 months and carries a significant risk of bleeding. The rate of major and/or clinically insignificant bleeding events is reported to be between 8.1 to 9.7% during initial treatment. This treatment is constraining because of the subcutaneous injections, drug interactions and blood test monitoring that this treatment requires. Direct oral anticoagulants are easier to use and do not require these blood tests.

Rivaroxaban and apixaban are two direct oral anticoagulants. Each of these drugs has been shown to be separately effective and safe compared to standard treatment. Comparison of bleeding rates between studies would favour the use of apixaban over rivaroxaban (4.3 versus 8.1%). However, the limitations of the trials and the lack of direct comparison between these two agents prevent definitive conclusions from being drawn, which means that these two drugs are considered standard drugs for the treatment of venous thromboembolism. This represents a dilemma for clinical practice because of the absence of convincing differences in safety has created real uncertainty about the nature of the risk/benefit ratio of direct oral anticoagulants. To address this clinical balance, a randomized controlled trial comparing apixaban and rivaroxaban to verify the safety of each is needed.

Intervention

Patients will be randomized to one of the two groups:

  1. Group receiving apixaban: 10 mg oral, twice daily for 1 week, then 5 mg oral, twice daily for the remainder of the 3 months of treatment;
  2. Group receiving rivaroxaban: 15 mg oral, twice daily for 3 weeks, then 20 mg oral for the remainder of the 3 months of treatment.

The main measure of the research project is the rate of relevant bleeding events, as defined by a major bleeding event and/or a non-major but clinically significant bleeding event.

For the project, patients with deep vein thrombosis (proximal to the popliteal fold) OR pulmonary embolism (Proximal or segmented), and who are at least 18 years old are eligible for the study. In addition, in order to be included, patients must not have received anticoagulants for more than 72 hours, must not have a creatine clearance rate < 30 mL/min and must not have any contraindications to receive oral anticoagulants.