Impact of polypharmacy on clinical outcomes in elderly patients with nonvalvular atrial fibrillation: sub-analysis of the ANAFIE Registry

Abstract

Abstract Background Elderly patients with AF often have multimorbidities leading to treated by polypharmacy, which has been reported to be associated with worse prognosis. Although stroke prevention is a cornerstone of optimal anticoagulation management, data on elderly NVAF patients aged ≥75 years with polypharmacy are lacking. Purpose The All Nippon Atrial Fibrillation In the Elderly (ANAFIE) Registry is a prospective, multicenter, observational study that seeks to elucidate real-world data on the clinical status and prognosis of more than 30,000 Japanese patients (aged ≥75 y) with NVAF. This sub-analysis of the ANAFIE Registry assessed 2-year outcomes and the status of anticoagulant management in elderly NVAF patients in view of polypharmacy. Methods A total of 32,275 patients from the ANAFIE Registry were divided into 3 groups by the number of concomitant medicines other than oral anticoagulants (OAC) (0 to 4, 5 to 8, ≥9 medicines). The annualized incidence rates of clinical outcomes were determined by Kaplan-Meier analysis. Hazard ratios (HR) for clinical outcomes were determined using the Cox proportional-hazards model. Results In the overall population, the mean age was 81.5 y; men accounted for 57.3%; the mean CHA2DS2-VASc score was 4.5; the mean HAS-BLED score was 1.9; the prevalence of paroxysmal AF was 42.1%; the mean follow-up period was 1.88 y; oral anticoagulants (OAC) were used by 92.4% of patients (WF, 25.5%; DOAC, 66.9%); the major concomitant medicines were antihypertensive drugs (70.9%), antiarrhythmic drugs (56.2%), dyslipidemia drugs (37.1%), and proton pump inhibitors (36.6%). The numbers of patients using 0 to 4, 5 to 8, and ≥9 concomitant medicines were 12,186 (37.8%), 13,597 (42.1%), and 5,636 (17.5%), respectively. As the number of concomitant medicines increased, the prevalence of comorbidities and renal dysfunction of creatinine clearance <50 mL/min increased. With an increase in concomitant medications, use of WF increased and that of DOAC decreased. Overall annualized incidence rates (% per patient-year) of clinical outcomes were 1.62 for stroke or systemic embolic events (SEE), 1.08 for major bleeding, 5.91 for cardiovascular (CV) events, 1.08 for CV death, and 3.71 for all-cause mortality. The annualized incidence rates and HR for each clinical outcome are shown in the table. As the number of concomitant medicines increased, the incidence for major bleeding, gastrointestinal bleeding, CV events, and all-cause death were significantly increased. Conclusions In elderly NVAF patients from the ANAFIE registry, polypharmacy was associated with increased risks of major bleeding, CV events, CV death, and all-cause mortality. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Daiichi Sankyo Co., Ltd.