Risk factors of major bleeding in elderly atrial fibrillation patients from the ANAFIE registry

Abstract

Abstract Background Bleeding is associated with shorter life expectancy during anticoagulant treatment in atrial fibrillation (AF) patients. Prior studies showed bleeding during anticoagulant treatment occurred more frequently in elderly AF patients than in younger AF patients. HAS-BLED score is a risk assessment tool for bleeding. However, since it was developed from the database of patients with warfarin, it has not been clarified whether this score is applicable in the era of direct oral anticoagulant (DOACs), especially for elderly AF patients. Purpose All Nippon AF In the Elderly (ANAFIE) registry was designed to obtain real-world information regarding patients with non-valvular AF (NVAF) aged ≥75 years, including current status of anticoagulant therapy and prognosis. The present study aimed to determine factors that associate with major bleeding for elderly NVAF patients using the dataset of ANAFIE registry conducted in Japan. Methods Total of 32,099 patients aged ≥75 years with NVAF were enrolled in ANAFIE registry, and followed for 2 years. Incidence rates of major bleeding for total population, <85 years old group and ≥85 years old group were estimated using Kaplan-Meier method. Cox proportional hazards model was used to determine independent predictors of major bleeding. The factors included in the model were selected by backward elimination procedure. Results Mean age was 81.5 years. 23,738 (74.0%) was <85 years old and 8,361 (26.0%) was ≥85 years old. 92.5% of whole population used anticoagulants including warfarin (27.6%) or DOACs (72.3%). Major bleeding occurred in 279 patients at 12 months with 189 in <85 years and 90 in ≥85 years old group. The cumulative incidence rate of major bleeding at 12 months by Kaplan-Meier method was 0.9% in whole patients, and was slightly higher in ≥85 years than in <85 years old group (1.1% vs 0.8%). In multivariate analysis of the whole patients, history of major bleeding (hazard ratio [HR]: 2.17), severe hepatic dysfunction (HR: 3.62), malignancy (HR: 1.52), falling within a year (HR: 2.07), antiplatelet use (HR: 1.37) and warfarin use (HR: 1.81) emerged as independent predictors of major bleeding. Severe hepatic dysfunction (HR: 9.17), HbA1c <6.0% (HR: 2.19) and dementia (HR: 2.00) were associated with major bleeding in patients only in aged ≥85 years. On the other hand, proton pump inhibitor use (HR: 1.36), creatinine clearance <30 mL/min (HR: 1.53) and polypharmacy (HR: 1.61) were associated with major bleeding only in those aged <85 years. Conclusion Among elderly (≥75 years old) Japanese NVAF patients in the era of DOACs, prior major bleeding, severe hepatic dysfunction, malignancy, falling within a year, antiplatelet use and warfarin use were identified as independent predictors of major bleeding. Impact of some predictors differed between the 2 age groups (<85 years vs ≥85 years). Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Daiichi Sankyo Co., Ltd.