Atrial fibrillation-related stroke : long-term prognosis and novel risk factors

Abstract

Stroke remains one of the leading causes of death and disability worldwide. Approximately 62% of strokes are ischemic, and atrial fibrillation (AF)-related ischemic strokes account for about 20% of all ischemic strokes. Since the publication of the RELY trial in 2009, the prevention of thromboembolic events for patients with non-valvular AF (NVAF) has entered a new era. Direct oral anticoagulants (DOACs) are characterized by rapid onset and offset, fewer drug-drug and drug-food interactions, and no need for regular INR monitoring compared to traditional vitamin K antagonists, such as warfarin. In large randomized controlled trials and multiple real-world studies, DOACs have been demonstrated to be safe and effective for primary and secondary prevention in patients with NVAF. For patients treated with DOACs, renal function is crucial, as all DOACs are excreted by the kidneys to varying degrees. Additionally, air pollution has emerged as a novel and modifiable risk factor for stroke. This thesis sought to investigate the different efficacy and safety profiles of individual DOACs, the safety and efficacy of DOACs among the oldest old patients (aged ≥85), the impact of longitudinal renal function variability on patients with NVAF and recent ischemic stroke, and whether long-term exposure to air pollution is associated with the risk of AF-related ischemic stroke and its impact on stroke severity, post-stroke disability, and short-term clinical outcomes. In the first study, 1,411 patients with NVAF following recent transient ischemic attack (TIA)/ischemic stroke who were prescribed DOACs were recruited. Apixaban and dabigatran were both associated with a lower risk of recurrent ischemic stroke/systemic embolism compared with rivaroxaban. Among the 1,596 oldest old patients (aged ≥ 85) with NVAF and recent TIA/ischemic stroke in the second study, DOACs were found to be safe and effective compared with antiplatelet agents and warfarin. The third study involved 3,809 patients with NVAF and recent TIA/ischemic stroke. Greater estimated glomerular filtration rate variability was found to be associated with increased risks of recurrent ischemic stroke/systemic embolism, total bleeding, MACE, cardiovascular, non-cardiovascular, and all-cause mortality. In the fourth study, 2,958 patients with ischemic stroke were included. Long-term exposure to particulate matter with an aerodynamic diameter of < 2.5 μm (PM2.5) and black carbon were found to be associated with an increased risk of cardioembolic stroke relative to stroke due to large artery atherosclerosis (LAA). Taken together, the findings of this thesis indicate that different DOACs vary in their safety and efficacy profiles. DOACs are safe and effective for the oldest-old NVAF patients with recent ischemic stroke. Increased renal function variability is associated with worse clinical outcomes. Additionally, ambient air pollution is a risk factor for cardioembolic stroke compared to stroke due to LAA.