Atrial fibrillation (AF) is a disease in which patients suffer from an irregular heartbeat, and this makes them prone to experiencing a stroke. In order to reduce the risk of stroke, these patients are often treated with medications called anticoagulants, which include the traditional vitamin-K antagonists (VKA), and the newer novel oral anticoagulants (NOAC). Whereas VKA are well studied, the effectiveness and safety of NOAC are less well established. Using real-world information from the UK, this study will compare how effective NOAC and VKA are in preventing stroke in patients with AF. This study will also compare how frequently these two types of anticoagulants cause undesirable side effects such as uncontrolled bleeding. In addition to evaluating the general AF population, this study will also examine subgroups of vulnerable AF patients who experience a higher risk of stroke and/or bleeding side effects. These include those who have already had a previous stroke, and those with chronic kidney disease. By comparing the effectiveness and safety of NOAC and VKA, this study will equip health care providers with evidence that will help them determine which anticoagulant would be most appropriate for each of their individual AF patients.
We will create a cohort of all adult AF patients with a first-time prescription for NOAC or VKA between 1 August 2011 and 30 September 2016. Patients newly exposed to NOAC at cohort entry will be matched on high-dimensional propensity score in a 1:1 ratio to patients newly exposed to VKA. The main outcomes of interest will be ischemic stroke/systemic embolism and bleeding, which will be assessed separately. A Poisson model will be used to calculate cumulative incidence rates in patients newly exposed to NOAC and VKA. Cox regression will be used to estimate the hazard ratio of each individual outcome, in patients exposed to NOAC compared to patients exposed to VKA. Separate models will be constructed using different measures of exposure. In the first model, patients will be censored when stopping or switching anticoagulant treatment group whereas in the second model, exposure to anticoagulant will be time-dependent. All analyses will be conducted for the general AF population, as well as for subgroups of AF patients with chronic kidney disease, and a history of stroke/transient ischemic attack. Several sensitivity analyses will be conducted to evaluate the robustness of the primary results.
Ischemic stroke/systemic embolism; Intracerebral bleeding; Myocardial infarction; Major bleeding; All-cause mortality.
Samy Suissa - Chief Investigator - Sir Mortimer B Davis Jewish General Hospital
Christel Renoux - Corresponding Applicant - McGill University
James Brophy - Collaborator - McGill University
Simone Loo - Collaborator - McGill University
Sophie Dell'Aniello - Collaborator - McGill University