Elderly Non-valvular Atrial Fibrillation Patients Research Articles

Gastrointestinal bleeding in elderly patients with atrial fibrillation: prespecified All Nippon Atrial Fibrillation in the Elderly (ANAFIE) Registry subgroup analysis

Gastrointestinal (GI) bleeding control is critical in elderly patients with atrial fibrillation (AF) receiving oral anticoagulants (OAC). This subgroup analysis aimed to clarify the actual state and significance of GI bleeding in elderly non-valvular AF (NVAF) patients. We evaluated the incidence and risk factors of GI bleeding during the 2-year follow-up and examined the GI bleeding impact on mortality. Of the 32,275 patients in the ANAFIE Registry, 1139 patients (3.5%) experienced GI bleeding (incidence rate, 1.92 events per 100 person-years; mean follow-up, 1.88 years); 339 upper and 760 lower GI bleeding events occurred. GI bleeding risk factors included age ≥ 85 years, body mass index ≥ 25.0 kg/m2, prior major bleeding, hyperuricaemia, heart failure, P-glycoprotein inhibitor use, GI disease, and polypharmacy (≥ 5 drugs). No significant differences in GI bleeding risk were found between direct OAC (DOAC) vs warfarin users (adjusted hazard ratios [95% confidence interval], 1.01 [0.88–1.15]). The 1-year post-GI bleeding mortality rate was numerically higher in patients with upper (19.6%) than lower GI bleeding (8.9%). In elderly Japanese NVAF patients, this large-scale study found no significant difference in GI bleeding risk between DOAC vs. warfarin users or 1-year mortality after upper or lower GI bleeding.

Pharmacokinetics of Edoxaban 15 mg in Very Elderly Patients with Nonvalvular Atrial Fibrillation: A Subanalysis of the ELDERCARE-AF Study.

We evaluated the pharmacokinetics (PK) of low-dose (15 mg) edoxaban in very elderly patients (≥80 years) with nonvalvular atrial fibrillation (NVAF) and high bleeding risk. This subanalysis of the phase 3, randomized, double-blind, placebo-controlled, multicenter ELDERCARE-AF study evaluated edoxaban plasma concentrations and compared them with the Japanese population of the ENGAGE AF-TIMI 48 and Japanese severe renal impairment (SRI) studies. The PK analysis population included 451 patients, 53.8% of whom concomitantly used antiplatelet drugs, 41.0% had SRI, and 38.0% had low body weight. Edoxaban plasma concentrations at trough and 1 to 3 hours post-dose in ELDERCARE-AF were 17.3 ± 13.9 (n = 427) and 93.3 ± 57.8 ng/mL (n = 447), respectively. These values were slightly higher than the 15 mg group in ENGAGE AF-TIMI 48 (n = 79; 12.4 ± 12.1 and n = 115; 78.7 ± 45.0 ng/mL, respectively), lower than the ENGAGE AF-TIMI 48 high-dose reduced to 30 mg group (n = 83; 25.1 ± 36.6 and n = 111; 150 ± 91.6 ng/mL, respectively), but similar to the Japanese SRI study (n = 39; 18.4 ± 11.2 and n = 40; 96.8 ± 48.3 ng/mL, respectively). ELDERCARE-AF patients with SRI and low body weight (≤45 kg) had higher concentrations than those without, and those taking antiplatelet drugs had lower concentrations than those who were not. PK data support edoxaban 15 mg once daily for very elderly NVAF patients with high bleeding risk, with caution for patients with SRI and/or low body weight.

Standardized community management on the diagnosis, treatment, and risk factors control for non-valvular atrial fibrillation in elderly patients

BackgroundBy investigating the knowledge, medication, occurrence of complications, and risks among elderly non-valvular atrial fibrillation (NVAF) patients in Shanghai communities, and providing standardized comprehensive management and follow-up, we aim to explore the impact of standardized community management on improving disease awareness, standardizing atrial fibrillation (AF) treatment, reducing the risk of complications occurrence, and addressing risk factors for AF patients.MethodsThis research selected elderly atrial fibrillation patients from Zhuanqiao Community Health Service Center, Minhang District, Shanghai from July 2020 to October 2022. Their personal health records and examination results were reviewed, and the incidence of AF, awareness, medication, and complications were investigated. Age-adjusted Charlson Comorbidity Index (aCCI), CHA2DS2-VASc score, and HAS-BLED score were used to evaluate disease burden, thromboembolic risk, and bleeding risk, respectively. The patients were subjected to standardized community management, and the compliance rate of disease awareness, treatment, resting heart rate, blood pressure, fasting blood glucose, and body mass index (BMI) were assessed at the baseline, 6 months and 1 year after management.ResultsA total of 243 NVAF patients were included, with an average aCCI score of (4.5 ± 1.1). Among them, 28% of the patients were aware of their AF, and 18.1% of the patients were aware of the hazards of AF. Of the patients, 11.9% used anticoagulant drugs, including 6.6% and 5.3% for warfarin and non-vitamin K antagonist oral anticoagulants (NOACs), respectively. 7% of patients used antiplatelet drugs. 26.7% of the patients used heart rate control drugs. 10.3% of the patients experienced thromboembolic events, and 0.8% of the patients experienced bleeding events. 93.0% of the patients were at high risk of thromboembolism, and 24.7% of the patients were at high risk of bleeding. Compared with the baseline, there were significant statistical differences (P < 0.001) in disease awareness, awareness of the hazards of AF, use of anticoagulant drugs and heart rate control drugs, and control of risk factors among NVAF patients after standardized community management. Moreover, with the extension of management time, there was a linear increase in the awareness of NVAF, awareness of the hazards of AF, utilization rate of anticoagulant drugs, utilization rate of heart rate control drugs, blood pressure, blood glucose, and BMI compliance rate (P < 0.001).ConclusionCurrently, the awareness, treatment, and control of risk factors for AF in elderly NVAF patients in Shanghai community are not satisfactory. Standardized community management helps to improve the diagnosis, treatment, and control of risk factors in AF.

Abstract 16694: Impact of Frailty in Non-Valvular Atrial Fibrillation Elderly Patients on Anticoagulation Therapy

Background: As the number of elderly people increases, we see more chances to consider anticoagulant therapy for elderly people with frailty. Research Question: Does frailty affect the outcome of anticoagulation therapy? Goals: To show the impact of frailty to the effectiveness and safety of anticoagulant therapy with rivaroxaban in elderly Japanese non-valvular atrial fibrillation (NVAF) patients. Methods: The GENERAL (GENeral practitioners and Embolism pRevention in NVAF patients treated with RivAroxaban: real-Life evidence) study was an observational study of elderly NVAF patients with rivaroxaban at general practice settings in Japan. We employed multiple imputation for missing baseline characteristics, and propensity score (PS) matching to estimate the treatment effect of frailty accounting for the patients’ imbalance. In each imputed and PS matched data set, the treatment effects of frailty were assessed with Cox proportional hazard models for each outcome. Results: A total of 5,717 (mean 79.3 years old, male 64.8%) were observed for a mean of 2.0 years and up to 3 years. Of these, 485 (8.5%) were classified frailty. Variable missing rates ranged from 0% to 35%. After the imputation and matching, the patients' backgrounds were well matched and balanced between two groups. Frailty was not associated with the primary endpoint: stroke/systemic embolism (Hazard Ratio [HR] 1.128, 95% Confidence Interval [CI]: 0.500 - 2.547, p=0.767). Also, frailty was not associated with all-secondary endpoints (Figure 1). In the sensitivity analyses with the complete cases, the cases with any missing variables were deleted, frailty was significantly related with outcome events except for the bleeding events (Figure 2). Conclusion: In our study results, frailty did not affect the effectiveness or safety of anticoagulant therapy with rivaroxaban for this population. However, we should consider the necessity and benefit for this population to start anticoagulant therapy.

Management and Anticoagulation Treatment of Non-Valvular Atrial Fibrillation in Elderly Patients: The Dali Study.

Non-valvular atrial fibrillation (NVAF) is associated with increased stroke in elderly populations, yet anticoagulant therapy is underutilized. We analyzed clinical characteristics and anticoagulation treatment rates of elderly NVAF patients hospitalized in Dali, China, to identify potential contributing factors. We collected data for 155 elderly patients with NVAF aged ≥60 years, from July 01, 2020, to December 31, 2021. We analyzed the awareness rate, clinical characteristics, and anticoagulant treatment rate of atrial fibrillation (AF), and identified factors influencing treatment. Patients were followed up one year after discharge to assess vital status, cardiovascular events, and anticoagulation therapy status. Among 155 patients, 52.26% were female, and the average age was 75.77 years. The awareness rate of AF was 47.74% at admission, and only 21.94% received anticoagulant therapy. After discharge, the rate of anticoagulant therapy significantly increased to 70.97%, and 89.09% used new oral anticoagulants. Thromboembolic history and persistent AF predicted anticoagulant therapy at discharge, while male gender, previous bleeding history, and antiplatelet therapy predicted non-anticoagulant therapy. Out of 133 patients who completed a one-year follow-up, 23.31% died, 3.01% had strokes, and 3.01% experienced bleeding. Anticoagulant therapy decreased to 51.96% during the follow-up year. Our findings highlight the low awareness rate and anticoagulant treatment rate, and high mortality among elderly NVAF patients in Dali. The development of comprehensive intervention strategies is critical to standardize AF management and improve prognosis.

Anticoagulant therapy and home blood pressure-associated risk for stroke/bleeding events in elderly patients with non-valvular atrial fibrillation: the sub-cohort study of ANAFIE registry

The benefits of direct oral anticoagulants (DOACs) and warfarin in elderly Japanese patients with non-valvular atrial fibrillation (NVAF) and high home systolic blood pressure (H-SBP) are unclear. This sub-cohort study of the ANAFIE Registry estimated the incidence of clinical outcomes in patients receiving anticoagulant therapy (warfarin and DOACs) stratified by H-SBP levels (<125 mmHg, ≥125–<135 mmHg, ≥135–<145 mmHg and ≥145 mmHg). Of the overall ANAFIE population, 4933 patients who underwent home blood pressure (H-BP) measurements were analyzed; 93% received OACs (DOACs: 3494, 70.8%; warfarin: 1092, 22.1%). In the warfarin group, at <125 mmHg and ≥145 mmHg, the respective incidence rates (per 100 person-years) were 1.91 and 5.89 for net cardiovascular outcome (a composite of stroke/systemic embolic events (SEE) and major bleeding), 1.31 and 3.39 for stroke/SEE, 0.59 and 3.91 for major bleeding, 0.59 and 3.43 for intracranial hemorrhage (ICH), and 4.01 and 6.24 for all-cause death. Corresponding incidence rates in the DOACs group were 1.64 and 2.65, 1.00 and 1.88, 0.78 and 1.69, 0.55 and 1.31, and 3.43 and 3.51. In warfarin-treated patients, the incidence rates of net cardiovascular outcome, stroke/SEE, major bleeding, and ICH were significantly increased at H-SBP ≥ 145 mmHg versus <125 mmHg. In the DOAC group, although there was no significant difference between H-SBP < 125 mmHg and ≥145 mmHg, the incidence rates of these events tended to increase at ≥145 mmHg. These results suggest that strict BP control guided by H-BP is required in elderly NVAF patients receiving anticoagulant therapy.

Efficacy and safety of long-term warfarin anticoagulation in elderly non-valvular atrial fibrillation patients.

Efficacy and safety of long-term warfarin anticoagulation in elderly non-valvular atrial fibrillation patients.

Renal Function and Clinical Outcomes Among Elderly Patients With Nonvalvular Atrial Fibrillation From ANAFIE

BackgroundAdvancing age, decreasing renal function, and atrial fibrillation are strongly associated. Real-world evidence of direct oral anticoagulant (DOAC) use among elderly patients ≥75 years of age with nonvalvular atrial fibrillation and renal dysfunction is limited. ObjectivesThis study sought to assess 2-year outcomes and anticoagulant treatment, stratified by renal function. MethodsEnrolled patients were divided into 4 subgroups by creatinine clearance (CrCl) to determine the impact of renal dysfunction on clinical outcomes. ResultsOf 32,275 patients, 26,202 with CrCl data were analyzed (median follow-up 2.00 [IQR: 1.92-2.00] years); 1.3% of patients had CrCl <15 mL/min, 10.7% had CrCl 15 to <30 mL/min, 33.4% had CrCl 30 to <50 mL/min, 35.8% had CrCl ≥50 mL/min, and 18.9% had unknown CrCl. Cumulative incidences of stroke/systemic embolic events, major bleeding, major plus clinically relevant nonmajor bleeding, cardiovascular death, all-cause death, and net clinical outcomes increased with decreasing CrCl. In multivariable Cox regression analysis, lower CrCl emerged as an independent risk factor for these clinical outcomes, except for major bleeding, compared with CrCl ≥50 mL/min. The effectiveness and safety of DOACs over warfarin were similar or better across 3 CrCl subgroups with CrCl 15 mL/min or more. DOAC use was associated with a lower risk of stroke/systemic embolic events, major bleeding, cardiovascular death, all-cause death, and net clinical outcome compared with warfarin in patients with CrCl 30 to <50 mL/min. ConclusionsIncidences of major clinical outcomes increased with decreasing renal function in elderly nonvalvular atrial fibrillation patients. DOACs were effective and safe even in patients with renal dysfunction (CrCl 15-<50 mL/min). (Prospective Observational Study in Late-Stage Elderly Patients with Non-Valvular Atrial Fibrillation: All Nippon AF In Elderly Registry [ANAFIE Registry]; UMIN000024006)

Clinical phenotypes of older adults with non-valvular atrial fibrillation not treated with oral anticoagulants by hierarchical cluster analysis in the ANAFIE Registry.

Although anticoagulants are indicated for many elderly patients with non-valvular atrial fibrillation (NVAF), some patients do not receive anticoagulant therapy, whose characteristics and outcomes are diverse. In this sub-analysis of the All Nippon AF In the Elderly (ANAFIE) Registry, the phenotypes of patients who were not receiving anticoagulants at baseline were evaluated by cluster analysis using Ward's linkage hierarchical algorithm. Of 32,275 enrolled patients, 2445 (7.6%) were not receiving anticoagulants. Two clusters were identified: (1) elderly paroxysmal AF (PAF) patients with a high proportion of catheter ablation history (57%) and (2) very elderly patients with a high prevalence of previous major bleeding (43%). Respective mean ages were 80.9 and 84.2 years, mean CHA2DS2-VASc scores were 3.8 and 4.9, PAF prevalences were 100.0% and 31.4%, proportions of patients with catheter ablation history were 21.0% and 7.9%, and proportions of patients with a history of major bleeding were 4.0% and 10.8%. Annual incidence rates were 2.72% and 8.81% for all-cause death, 1.66% and 5.85% for major adverse cardiovascular or neurological events, 1.08% and 3.30% for stroke or systemic embolism, and 0.69% and 1.19% for major bleeding, respectively. In this cohort of elderly NVAF patients from the ANAFIE Registry who were not receiving anticoagulants, over half had PAF with a high proportion of catheter ablation history and a low incidence of adverse outcomes; for them, non-prescription of anticoagulants may be partially understandable, but they should be carefully monitored regarding AF burden or atrial cardiomyopathy and be adequately anticoagulated when adverse findings are detected. The remaining were very elderly patients with a high prevalence of previous major bleeding and a high incidence of adverse outcomes; for them, non-prescription of anticoagulants is inappropriate because of the high thromboembolic risk. Registration: http://www.umin.ac.jp/; Unique identifier: UMIN000024006.

Predictive value of neutrophil-to-apolipoprotein A1 ratio in all-cause and cardiovascular death in elderly non-valvular atrial fibrillation patients

Neutrophil-to-apolipoprotein AI ratio’s (NAR’s) predictive value for the elderly non-valvular atrial fibrillation (NVAF) patients' death has not been fully recognized. We consecutively enrolled 1224 elderly patients with NVAF (≥75 years). With an average follow-up of 733.35 ± 271.39 days, 222 all-cause deaths were identified. Among these, 101 were caused by cardiovascular diseases. Cox regression showed that after correcting for potential confounders, patients in the Q4 group had an increased all-cause (hazard ratio [HR] = 1.90, 95% confidence interval [CI]: 1.20–2.99) and cardiovascular death (HR = 2.59, 95% CI: 1.30–5.15) risk compared to those in the lowest NAR quartile. Kaplan–Meier analysis indicated that all-cause and cardiovascular death were higher in the high NAR than those in the lowest NAR category (log rank, all, P < 0.001). A nonlinear association was observed between death and NAR. NAR may be a promising predictive biomarker for identifying elderly NVAF patients with poor clinical prognoses.

Prognostic impact of heart rate during atrial fibrillation on clinical outcomes in elderly non-valvular atrial fibrillation patients: ANAFIE Registry sub-cohort study

BackgroundElderly patients with atrial fibrillation (AF) are at a higher risk for all-cause mortality and heart failure. Rate control is an essential component in AF management. This exploratory study assessed the relationship between resting heart rate during AF at baseline and clinical outcomes in Japanese elderly non-valvular AF (NVAF) patients, using the All Nippon AF In the Elderly Registry (ANAFIE) dataset. MethodsThis sub-cohort included patients who agreed to participate and presented with AF at enrollment in the ANAFIE study. They were categorized into six groups according to the resting heart rate during AF. Outcomes included 2-year cumulative incidences of stroke/systemic embolic events (SEE), ischemic stroke, major bleeding, cardiovascular (CV) events, CV death, all-cause death, and net clinical outcome, a composite of stroke/SEE, major bleeding, and all-cause death. ResultsOf the 8292 patients included in this sub-cohort (paroxysmal, 1496; non-paroxysmal, 6796), 90 % of patients were using anticoagulants. Higher heart rate was more frequently reported in women and in patients with paroxysmal AF and was associated with increased use of direct oral anticoagulants (DOACs) and antiarrhythmic drugs. Heart rate ≥110 beats per minute (bpm) was associated with a significantly higher incidence of cardiac events and numerically higher incidences of CV death and all-cause death compared with a heart rate of 60 to <80 bpm, all of which were driven by an increased risk in patients with non-paroxysmal AF. Hazard ratios by the type of anticoagulant for each clinical outcome were comparable across all heart rate categories, indicating no significant interactions. ConclusionsElderly Japanese patients with non-paroxysmal NVAF and a heart rate ≥110 bpm have an increased risk of cardiac events. There was no interaction between heart rate category and the relative risk of adverse clinical events in patients taking DOACs compared with those taking warfarin.

Oral Anticoagulants in Very Elderly Nonvalvular Atrial Fibrillation PatientsWith High Bleeding Risks: ANAFIE Registry.

Data on the effectiveness and safety of oral anticoagulant (OAC) agents in very elderly nonvalvular atrial fibrillation patients with high bleeding risk are lacking. This study examined 2-year outcomes and effects of OAC agents among these patients using the ANAFIE (All Nippon Atrial Fibrillation in the Elderly) registry (N=32,275) data. Patients were classified into high-risk (age:≥80 years; CHADS2 score:≥2; and presence of≥1 bleeding risk factor: creatinine clearance of 15-30mL/minute, prior bleeding at critical sites, body weight of≤45kg, or continuous antiplatelet use) and reference groups. In the high-risk (n=7,104) and reference (n=25,171) group patients, 89.0% and 93.4%, respectively, used OAC agents. Of these, respectively, 30.1% and 24.2% used warfarin, and 58.9% and 69.1% used direct-acting OAC (DOAC) agents. Compared with the reference group, the high-risk group had higher incidences of stroke/systemic embolism, major bleeding, intracranial hemorrhage, gastrointestinal bleeding, cardiovascular events, and all-cause death. In the high-risk group, DOAC agent use vs nonuse of OAC agents was associated with reduced incidences of stroke/systemic embolism (HR: 0.53; 95%CI: 0.36-0.79) and all-cause death (HR: 0.65; 95%CI: 0.52-0.81) but not with major bleeding (HR: 1.09; 95%CI: 0.63-1.89). DOAC agents were superior to warfarin in effectiveness and safety. For high-risk patients, history of major bleeding, severe liver dysfunction, and falls within 1 year were independent risk factors for major bleeding. High-risk elderly nonvalvular atrial fibrillation patients had higher event incidences. DOAC agents were associated with reduced risk of stroke/systemic embolism and all-cause death vs nonuse of OAC agents or warfarin. (Prospective Observational Study in Late-Stage Elderly Patients With Nonvalvular Atrial Fibrillation [ANAFIE registry]; UMIN000024006).

Clinical phenotypes of older adults with non-valvular atrial fibrillation not treated with oral anticoagulants by hierarchical cluster analysis in the ANAFIE registry

Abstract Background and purpose The All Nippon AF In the Elderly (ANAFIE) registry evaluated the current status of anticoagulant therapy in older adult patients (aged ≥75 years) with non-valvular atrial fibrillation (NVAF) in Japan. Although older adult NVAF patients requires anticoagulation therapy, some of them do not receive it and the reasons would be diverse. Therefore, we aimed to identify the phenotypes of older adult NVAF patients not treated with oral anticoagulants using data from the ANAFIE registry. Methods In this sub-analysis of the ANAFIE registry, the phenotypes of patients who were not receiving anticoagulants at baseline were evaluated by cluster analysis using Ward's linkage hierarchical algorithm. We used 20 categorical variables and 6 continuous variables for the cluster analysis which were used as the risk factors in the main analysis of the ANAFIE registry [1]. Results Of 33,275 enrolled patients, 2445 (7.3%) were not receiving anticoagulants. Two clusters were identified: (1) elderly paroxysmal AF (PAF) patients with a low prevalence of comorbidities (58%) and (2) very elderly patients with a high previous major bleeding prevalence (42%). For each cluster, mean ages were 79.9 and 85.7 years, mean CHADS2 scores were 2.3 and 3.1, PAF prevalences were 83% and 54%, heart failure prevalences were 18% and 48%, the proportions of patients with a history of major bleeding were 0% and 25%, the proportions of patients with a history of catheter ablation were 21% and 8%, respectively. Annual incidence rates of each cluster were 2.62% and 9.08% for all-cause death, 1.72% and 5.83% for major adverse cardiovascular or neurological events, 1.22% and 3.14% for stroke or systemic embolism, and 0.53% and 1.43% for major bleeding. Conclusions In this cohort of elderly NVAF patients not receiving anticoagulants, more than half (∼60%) were PAF patients and had a low incidence of adverse outcomes. The remaining ∼40% were characterized as very elderly patients with a high prevalence of previous major bleeding and a high incidence of adverse outcomes. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Daiichi Sankyo Co., Ltd.

Population Pharmacokinetics and Hemorrhagic Risk Analysis of Rivaroxaban in Elderly Chinese Patients With Nonvalvular Atrial Fibrillation.

Rivaroxaban is a popular direct factor Xa inhibitor used for anticoagulation therapy in patients with nonvalvular atrial fibrillation (NVAF). The aim of this study was to establish a population pharmacokinetic (PPK) model for rivaroxaban in elderly Chinese patients with nonvalvular atrial fibrillation, evaluate precision dosing regimens, and analyze hemorrhagic risk after rivaroxaban treatment. A 1-compartment population PK model with estimated glomerular filtration rate (eGFR), total bilirubin (TBIL), and ABCB1 rs1045642 as major covariates for apparent clearance was developed using the nonlinear mixed-effects model (NONMEM). A Monte Carlo simulation was performed to evaluate various dosing schemes and different levels of covariates for the target range of therapeutic drug-monitoring concentrations (Cmax,ss and Cmin,ss ). The exposure to rivaroxaban was simulated and assessed through hemorrhagic risk evaluation. The results showed that the average probability of target attainment (PTA) for optimal dosing regimens with different covariate levels for the targeted Cmax,ss and Cmin,ss were 29.35% to 31.3% and 64.91% to 65.8%, respectively. A dosage of 10mg of rivaroxaban in elderly Chinese patients with normal renal and liver function was appropriate. The area under the concentration-time curve estimated over 24hours with precision dosing at steady state (AUC24,ss ) was statistically significantly associated with an increased risk of bleeding events (OR1.0006, 95%CI 1.0003 to 1.001, P <.0001), and the bleeding risk increased by 1.82-fold for every 1000 μg*h/L increase in AUC24,ss . A lower dose is recommended for elderly patients with renal impairment to avoid overexposure and bleeding events. The PPK model could inform individualized dosing for elderly Chinese patients with nonvalvular atrial fibrillation receiving rivaroxaban anticoagulation therapy.

Prognosis of elderly non-valvular atrial fibrillation patients stratified by B-type natriuretic peptide: ELDERCARE-AF subanalysis

B-type natriuretic peptide (BNP) is a risk factor for stroke and cardiac death in patients with atrial fibrillation. We hypothesized the prognostic outcomes of very elderly non-valvular atrial fibrillation patients ineligible for standard anticoagulation treatment would vary according to BNP stratification. In this subanalysis of the ELDERCARE-AF trial, patients were stratified by BNP levels at enrollment, and clinical outcomes compared among BNP subgroups. Hazard ratios were adjusted for age, atrial fibrillation type, body mass index, creatine clearance, congestive heart failure, and D-dimer. BNP levels were measured using chemiluminescence enzyme immunoassays. In total, 984 patients (average age: 86.6 years) not considered eligible for oral anticoagulant therapy at approved doses for stroke prevention were included. The BNP levels at enrollment were <200 (low), 200 to <400 (moderate), and ≥400 (high) pg/mL in 428, 300, and 256 patients, respectively. The number (%) of patients with stroke or systemic embolism (SSE) was 7 (1.2%), 24 (5.9%), and 28 (8.6%) in the low, moderate, and high BNP subgroups, respectively (adjusted hazard ratio 3.82, P=.0025 for low vs moderate BNP and 4.76, P=.0007 for low vs high BNP). There was no significant difference in major bleeding incidence between the BNP subgroups. Edoxaban 15 mg was associated with a consistent reduction in SSE vs placebo in all BNP subgroups. Stratification by BNP level was associated with the incidence of SSE for very elderly non-valvular atrial fibrillation patients ineligible for standard anticoagulation treatment, and the effect of edoxaban 15 mg was consistent across BNP levels.

Effect of Cancer on Clinical Outcomes in Elderly Patients With Non-Valvular Atrial Fibrillation - Substudy of the ANAFIE Registry.

Data on outcomes for patients with atrial fibrillation (AF) and active cancer are scarce. The effect of active cancer on thrombosis and bleeding risks in elderly (≥75 years) patients with non-valvular AF (NVAF) enrolled in the All Nippon AF In the Elderly (ANAFIE) Registry were prospectively analyzed. In this subanalysis of the ANAFIE Registry, a prospective, multicenter, observational study conducted in Japan, we compared the incidence rates of clinical outcomes between active cancer and non-cancer groups. Relationships between primary outcomes and anticoagulation status were evaluated. Of the 32,725 patients enrolled in the Registry, 3,569 had active cancer at baseline; 92.0% of active cancer patients received anticoagulants (23.7%, warfarin; 68.2%, direct oral anticoagulants [DOACs]). Two-year probabilities of stroke/systemic embolic events (SEE) were similar in the cancer (3.33%) and non-cancer (3.16%) groups. Patients with cancer had greater incidences of major bleeding (2.86% vs. 2.04%), all-cause death (10.95% vs. 6.77%), and net clinical outcomes (14.63% vs. 10.00%) than those without cancer. In patients without cancer, DOACs were associated with a decreased risk of stroke/SEE, major bleeding, all-cause death, and net clinical outcome compared with warfarin. No between-treatment differences were observed in patients with active cancer. Active cancer had no effect on stroke/SEE incidence in elderly NVAF patients, but those with cancer had higher incidences of major bleeding events and all-cause death than those without cancer.

POSC245 Physician Preferences in Prescribing Oral Anticoagulation Therapy in Elderly Non-Valvular Atrial Fibrillation Patients with Comorbidities: A Clinical Vignette Study

To determine whether and how patient characteristics impact physicians’ decision to prescribe anticoagulants (AC) in elderly patients with non-valvular atrial fibrillation (NVAF), and the preference for type and dosing of AC.

Multi-Morbidity, Anti-Thrombotic Treatment, and Mortality Among the Elderly Non-Valvular Atrial Fibrillation Patients: Results from the KERALA-AF Registry Study

Multi-Morbidity, Anti-Thrombotic Treatment, and Mortality Among the Elderly Non-Valvular Atrial Fibrillation Patients: Results from the KERALA-AF Registry Study

Effectiveness and Safety of Apixaban Versus Warfarin in Obese Patients with Nonvalvular Atrial Fibrillation Enrolled in Medicare and Veteran Affairs

Real-world studies have evaluated the use of anticoagulants in obese patients with nonvalvular atrial fibrillation (NVAF), but they have been limited by sample size or the use of diagnosis codes on claims to define obesity. This retrospective study used body weight data of ≥100 kg or a body mass index of ≥30 kg/m2 to identify elderly (aged ≥65 years) NVAF patients with obesity in dually enrolled Veterans Affairs and fee-for-service Medicare patients. It evaluated the risk of stroke/systemic embolism (SE) and major bleeding (MB) in patients that initiated apixaban versus warfarin. Stabilized inverse probability treatment weighting was used to balance the baseline characteristics between patients prescribed apixaban and warfarin in obese patients. Cox models were used to evaluate the relative risk of stroke/SE and MB. Overall, 35.9% (n = 26,522) of the NVAF population were obese, of which 13,604 apixaban and 12,918 warfarin patients were included. After inverse probability treatment weighting, patient characteristics were balanced. The mean age was 75 years, the mean CHA2DS2-VASc score (Congestive Heart Failure, Hypertension, Age ≥75 [Doubled], Diabetes Mellitus, Prior Stroke or Transient Ischemic Attack [Doubled], Vascular Disease, Age 65-74, Female) was 3.8, the mean HAS-BLED (Hypertension, Abnormal Renal/Liver Function, Stroke, Bleeding History or Predisposition, Labile INR, Elderly, Drugs/Alcohol Concomitantly) Score was ∼2.6, and >98% of patients were males. Obese apixaban patients were associated with a similar risk of stroke/SE (hazard ratio: 0.82; 95% confidence interval: 0.66 to 1.03) and a significantly lower risk of MB (hazard ratio: 0.62; 95% confidence interval: 0.54 to 0.70) versus warfarin. No significant interaction was observed between treatment and obesity status (nonobese, obese/nonmorbid, obese/morbid) for stroke/SE (interaction p = 0.602) or MB (interaction p = 0.385). In obese patients with NVAF, apixaban was associated with a similar risk of stroke/SE and a significantly lower risk of MB versus warfarin.

Abstract 9071: Prognosis of Elderly Non-Valvular Atrial Fibrillation Patients Stratified by B-type Natriuretic Peptide Concentration: A Subanalysis of Data from the ELDERCARE-AF Trial

Introduction: B-type natriuretic peptide (BNP) is a known predictor of prognosis and disease severity in patients with heart failure. However, only limited data are available on the relation between BNP and outcomes in very elderly (age, ≥ 80 years) patients ineligible for standard anticoagulation with non-valvular atrial fibrillation (NVAF). Therefore we evaluated the prognostic and therapeutic outcomes of very elderly Japanese NVAF patients stratified by BNP concentration. Methods: This was a subanalysis of data from ELDERCARE-AF, a multicenter, randomized, double-blind, placebo-controlled phase 3 study of edoxaban 15 mg (once daily) in very elderly Japanese NVAF patients considered ineligible for standard anticoagulant treatment. Patients were stratified according to BNP concentration at enrollment, and their outcomes were compared. The primary efficacy endpoint was stroke or systemic embolism (SSE). The primary safety endpoint was major bleeding. Results: A total of 984 patients (mean age, 86.6 years) were randomized to edoxaban 15mg ( n = 492) or placebo ( n = 492). BNP concentration at enrollment was &lt; 200 pg/mL (low), 200 to &lt; 400 pg/mL (moderate), and ≥ 400 pg/mL (high) in 428, 300, and 256 patients, respectively. Mean CHADS 2 score was 2.9 in the low BNP and 3.2 in the moderate and high BNP groups. The incidences of SSE were 1.2%/patient-year (7/428), 5.9%/patient-year (24/300), and 8.6%/patient-year (28/256) in the low, moderate, and high BNP groups, respectively: unadjusted HR = 5.03 (95% confidential interval [CI], 2.17-11.67), P = 0.0002, for low versus moderate BNP; unadjusted HR = 7.07 (3.09-16.18), P &lt; 0.0001, for low versus high BNP. No significant intergroup differences were found for the incidence of major bleeding. Edoxaban 15mg was superior to placebo in preventing SSE in the moderate and high BNP groups: unadjusted HR, 0.27 (0.10-0.73), P &lt; 0.01, and unadjusted HR, 0.34 (0.15-0.81), P &lt; 0.05, respectively. There was no significant difference in major bleeding between the edoxaban 15mg and placebo groups. Conclusions: In very elderly NVAF patients, BNP concentration was positively related to the incidence of SSE, and edoxaban 15mg had a preventive effect, regardless of BNP concentration.