Effect of Polypharmacy on Clinical Outcomes in Elderly Patients With Non-Valvular Atrial Fibrillation

Background: This All Nippon AF in the Elderly (ANAFIE) Registry sub-analysis evaluated the impact of polypharmacy on 2-year outcomes in a large, elderly (aged >= 75 years) Japanese population with non-valvular atrial fibrillation (NVAF). Methods and Results: The ANAFIE Registry was a multicenter, prospective, observational study with a 24-month follow-up period. Of 32,275 enrolled NVAF patients, 31,419 were grouped by the number of prescribed concomitant medications (other than oral anti-coagulants [OACs]): 0-4 [38.8%], 5-8 [43.3%], and >= 9 [17.9%]). Patients receiving more concomitant medications were older, had poor renal function, and suffered more comorbidities than those receiving fewer concomitant medications. Several patient background factors, including diabetes mellitus, myocardial infarction, and chronic kidney disease, were significantly correlated with an increased number of concomitant medications. With increasing medications, OAC prescription rates decreased, but the warfarin prescription rate increased, and the cumulative incidence rates of stroke/systemic embolic events (SEE), major bleeding, gastrointestinal bleeding, fracture/falls, cardiovascular events, cardiovascular death, and all-cause death significantly increased (each, P<0.05). In multivariate analysis, increasing medications was independently associated with increases in these events, except for stroke/SEE. There were no significant interactions between the number of medications and anticoagulant treatment with direct OAC or warfarin concerning the incidence of these events. Conclusions: Polypharmacy was frequent among elderly patients with NVAF who were older with more comorbidities, and was independently associated with a higher incidence of extracranial events.