Interaction between chronic kidney disease and atrial fibrillation on incident stroke and all-cause mortality: Matched cohort study of 49,594 patients

Background and aims: The interaction between full-spectrum chronic kidney disease (CKD) and atrial fibrillation (AF) on ischemic stroke and all-cause mortality risk, particularly in stage 4 and 5 CKD, remains undetermined. Methods: This matched cohort study identified incident AF patients using the International Classification of Disease codes and electrocardiograms from the Clinical Research Data Repository of China Medical University Hospital between 2003 and 2020. For each AF patient, we selected four controls without AF and matched them by age, sex, eGFR within 10 mL/min/1.73 m(2), end-stage kidney disease (ESKD) vintage, and diagnosis year. Multivariable Cox proportional hazard models were utilized to assess the interaction between AF and CKD on three-year ischemic stroke and all-cause mortality outcomes. Results: Within a total of 10,155 patients and 39,439 controls, incidence rates were 3.03 % and 1.48 % for ischemic stroke and 15.6 % and 9.53 % for overall mortality, respectively. In AF, the stroke risk was the highest among patients with stage 4 and 5-ND (non-dialysis) CKD with adjusted hazard ratio (aHR) of 3.31 (95 % CI, 2.46-4.45) and 2.73 (1.88-3.96), respectively. The mortality risk difference varied between 45% and 177 % with the highest difference noted in ESKD (aHR 3.36 [95 % CI, 2.84-3.98] in AF vs. 1.59 [95 % CI, 1.28-1.96] in non-AF; interaction p < 0.001). Anticoagulation therapy significantly lowered the mortality risk among patients with AF and advanced CKD (3-way interaction p < 0.001). Conclusions: The risk of ischemic stroke and overall mortality was particularly high among patients with concurrent AF and stage 4 and 5-ND CKD, underscoring the urgent evidence to optimize prognosis.