Risk of major bleeds associated with the use of direct oral anticoagulants in venous thromboembolism

Date of Approval: 
2016-07-20 00:00:00
Lay Summary: 
Venous thromboembolism (VTE) is a term used to describe a blood clot typically occurring in a large vein in the legs or causing a sudden blockage of an artery supplying blood to the lungs. To prevent recurrence of these blood clots in patients who survive, a medication called warfarin has been used for more than 50 years. The use of warfarin is complicated by the need for frequent blood tests to make sure that the concentration of warfarin in the blood is sufficient to prevent clots but not too high which may result in serious bleeding. This limitation has led to the development of another class of drugs, the direct oral anticoagulants (DOACs), which do not require monitoring by blood tests. Despite the potential benefits of DOAC therapy in the treatment of VTE, our knowledge regarding its safety is limited compared to warfarin. The purpose of this study is to determine whether DOACs are associated with an increased risk of major bleeding, such as stroke from bleeding in the brain or bleeding from the stomach or bowel, as compared to warfarin.
Technical Summary: 
The objective of this study is to assess the safety of DOACs for the treatment of VTE using real-world, population-based data sources to inform policy development and clinical practice. We will conduct a matched cohort study to assess the safety of DOACs compared with vitamin K antagonists (VKA) such as warfarin among patients with incident VTE. The investigators will carry out separate population based cohort studies using administrative health databases in Canada, the United States (US), and the United Kingdom (UK). VKA-users will be matched to DOAC-users based on age, sex, date of cohort entry and propensity score. To determine the adjusted hazard of study outcomes with DOACs use (compared with VKA), we will perform multivariable Cox proportional hazards regression to estimate the hazard ratios and their corresponding 95% confidence intervals. Analyses will be performed separately at each of the participating CNODES sites according to a common analytical protocol and then pooled using meta-analysis.
Health Outcomes to be Measured: 
Hospitalization or visit to the emergency department for a major bleed All-cause mortality
Application Number: 

Samy Suissa - Chief Investigator - McGill University
Christel Renoux - Corresponding Applicant - McGill University
Brenda R Hemmelgarn - Collaborator - University of Calgary
Lisa Lix - Collaborator - University of Manitoba
Min Jun - Collaborator - University of Calgary
Pierre Ernst - Collaborator - McGill University
Sophie Dell'Aniello - Collaborator - McGill University

HES Accident and Emergency;HES Admitted Patient Care