Drug interactions with anticoagulant therapy are a major, preventable cause of harm. To improve knowledge on anticoagulant safety, we plan to conduct bidirectional self-controlled case series studies, among concomitant users of warfarin and a skeletal muscle relaxant and, as pre-specified negative control comparators, among concomitant users of an inhaled corticosteroid and a skeletal muscle relaxant. Each study will examine a composite outcome of venous thromboembolism / ischemic stroke.
Data will be obtained from both CPRD GOLD and CPRD Aurum with linkage to Hospital Episode Statistics and ONS mortality records. The study populations will consist of any individual initiating warfarin (the object drug of interest, the affected agent in a drug interaction pair) and inhaled corticosteroids (the prespecified negative control object drug). Among object drug users, we will define periods of exposure and non-exposure to skeletal muscle relaxants (precipitant drugs, affected agents in a drug interaction pair). We will limit each cohort to individuals experiencing the outcome of interest during their observation period.
We will dichotomise each day of the observation period as a risk or non-risk day, based on the presence or absence of exposure to a skeletal muscle relaxant. We will use conditional Poisson regression models to estimate incidence rate ratios and 95% confidence intervals and conduct sensitivity analyses to examine the robustness of our findings and assess potential violations of the self-controlled case series designs underlying assumptions.
Darren Ashcroft - Chief Investigator - University of Manchester
Matthew Carr - Corresponding Applicant - University of Manchester
Charles Leonard - Collaborator - University of Pennsylvania
Sean Hennessy - Collaborator - University of Pennsylvania
Warren Bilker - Collaborator - University of Pennsylvania