Comparative effectiveness and safety of non-vitamin K antagonist oral anticoagulants in stroke prevention in atrial fibrillation

• Applicant: Professor Dr. Antonios Douros
• Subject Area: Epidemiology and Medical Biometry/Statistics
• Term: from 2016 to 2018
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 327497361

The main objective of this research project is to compare the effectiveness and safety among the non-vitamin K antagonist oral anticoagulants (NOACs) dabigatran, rivaroxaban, and apixaban, and the vitamin K antagonist warfarin in patients with atrial fibrillation (AF) in routine clinical practice. AF is a common cardiac arrhythmia showing an increasing prevalence with advancing age, and it is a risk factor for stroke, heart failure, and mortality. Vitamin K antagonists such as warfarin have been the gold standard in the treatment of AF for many years. Recently, NOACs were also approved for this indication. In clinical trials NOACs reduced stroke or systemic embolic events, all-cause mortality, and intracranial hemorrhage compared to warfarin, but increased gastrointestinal bleeding. However, these trials as well as a few observational studies that followed have left several areas of uncertainty, including head-to-head-comparisons among different NOACs, NOAC use in the elderly as well as in patients with chronic kidney disease, and possible sex- or comedication-specific effects.The primary effectiveness outcome of our study will be a composite endpoint of stroke or systemic embolism, with secondary outcomes including ischemic stroke, systemic embolism, cardiovascular mortality, and all-cause mortality. The primary safety outcome will be major bleeding, with secondary outcomes including intracranial hemorrhage and gastrointestinal bleeding. A possible influence of age, sex, kidney function or specific comedications on safety and effectiveness of oral anticoagulants will be elucidated via sensitivity analyses. Three computerized healthcare databases from the Quebec region in Canada containing several millions of insurants will be used as data source. For risk quantification, nested case-control analyses will be conducted. The findings will add valuable information regarding the rational use of oral anticoagulants. Moreover, they will help us better evaluate benefits and risks of these drugs in populations often underrepresented in clinical trials such as older adults or patients with impaired kidney function.

• DFG Programme: Research Fellowships
• International Connection: Canada
• Host: Professor Samy Suissa