Oral anticoagulants for atrial fibrillation and the risk of fractures

Date of Approval
Application Number
Technical Summary

The objective of this study is to examine fracture risk with the use of oral anticoagulants for stroke prevention in patients with atrial fibrillation. We will assemble a cohort of patients newly-diagnosed with atrial fibrillation between 1998 and 2015 using the Clinical Practice Research Datalink (CPRD) with linkage to the Hospital Episode Statistics (HES) and the Office for National Statistics (ONS). Cohort entry will be defined by the date of atrial fibrillation diagnosis, as determined by Read codes in CPRD. Primary exposure will be defined in a time-dependent fashion as current use of vitamin K antagonists (VKA) or direct oral anticoagulants (DOACs), separately, and the reference group will be the use of antiplatelet drugs. The primary outcome will be the first hospitalization with a diagnosis of rib, spine, hip or wrist fracture, identified in HES by international classification of diseases-10 codes. Time-dependent Cox models will be used to assess the hazard ratio for hospitalized osteoporotic fractures associated with current use of VKA or DOACs, compared with antiplatelet use. Secondary analyses will include duration-response analyses of fracture risk with VKA and DOAC use, stratification of patients by age and history of osteoporosis, and stratification of the outcome by fracture type.

Health Outcomes to be Measured

The composite of rib, wrist, hip, and spine fractures identified in HES.


Samy Suissa - Chief Investigator - McGill University
Adi Klil-Drori - Collaborator - Sir Mortimer B Davis Jewish General Hospital
Hui Yin - Collaborator - Sir Mortimer B Davis Jewish General Hospital
Kristian Filion - Collaborator - McGill University
Laurent Azoulay - Collaborator - McGill University


HES Admitted Patient Care;ONS Death Registration Data