Oral anticoagulants for atrial fibrillation and the risk of fractures

Date of ISAC Approval: 
16/06/2016
Lay Summary: 
Strong blood thinners such as warfarin are known to work very well in reducing the risk of stroke in people who have atrial fibrillation (a condition characterized by an irregular and often rapid heart rate). Warfarin also increases the risk of bleeding, which is why physicians change the dose regularly according to the results of a specific blood test. However, there are reports that warfarin may also increase the risk of fractures, and that this risk cannot be predicted by the results of a routine blood test. Fractures in people taking blood thinners are important because their higher risk of bleeding makes it more complicate to operate. Also, fractures may cause subsequent disability, and stopping the blood thinner may bring back the risk of stroke. Also, three new blood thinners were approved in 2011 for stroke prevention in atrial fibrillation, and the risk of fractures with these medications is unknown. We will therefore conduct a study of patients with newly-diagnosed atrial fibrillation and compare the risk of fractures with warfarin and the new oral anticoagulants with that of aspirin or similar drugs.
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.
Collaborators: 

Samy Suissa - Chief Investigator - McGill University
Adi Klil-Drori - Researcher - Sir Mortimer B Davis Jewish General Hospital
Hui (Hoi) Yin - Researcher - Sir Mortimer B Davis Jewish General Hospital
Dr Kristian Filion - Researcher - McGill University
Dr Laurent Azoulay - Researcher - McGill University

Linkages: 
HES Admitted;ONS