Concurrent renal dysfunction with ischemic heart disease is an important determinant for cardiac and cerebrovascular mortality in patients on chronic digoxin therapy for atrial fibrillation

Background: Major adverse cardiac and cerebrovascular events (MACCEs) are main concerns in patients with atrial fibrillation (AF); however, factors affecting MACCEs remain inconclusive in AF patients chronically treated with digoxin. We investigated the major clinical determinants for fatal MACCEs in AF patients treated with digoxin over a 10-year follow-up period. Methods: We analyzed a retrospective cohort of 1,480 AF patients at Eulji University Hospital, Daejeon, South Korea from March 2004 to August 2015. Among this population, 402 consecutive patients receiving chronic digoxin therapy were selected for the study. Data for electrocardiography, medication history, laboratory values including the serum digoxin concentration (SDC) and fatal MACCEs were collected. All data were divided and compared between groups based on the occurrence of MACCEs. Results: The overall incidence of fatal MACCEs among the 402 digoxin-treated AF patients (age, 68 11 years; male, 40.3%) was 12.1%. These fatalities resulted from heart failure (46.1%), fatal stroke (26.9%), fatal myocardial infarction (15.3%) and sudden cardiac death (5.7%). A higher prevalence of diabetes, pre-existing ischemic heart disease (IHD), lower estimated glomerular filtration rate (eGFR), higher SDC, and junctional bradycardia were more frequently observed in patients with MACCEs compared to those without MACCEs. Multivariable analysis showed that an eGFR of 60 mL/min/1.73 m 2 and pre-existing IHD had a hazard ratio of 3.35 and a confidence interval of 1.64-6.87 (P < 0.001) for fatal MACCEs. Conclusion: Chronic kidney disease stage III-V with pre-existing IHD is significantly associated with increased cardiac and cerebrovascular mortality in AF patients with chronic digoxin use.