Atrial Fibrillation In Elderly Research Articles

Oral anticoagulants in extremely-high-risk, very elderly (>90 years) patients with atrial fibrillation

The prevalence and incidence of atrial fibrillation (AF) increase with age. However, older patients often are denied oral anticoagulation (OAC), especially if they are "very elderly" (age ≥90 years) and perceived to be high risk for bleeding, for example, those with a history of intracranial hemorrhage (ICH), gastrointestinal bleeding (GIB), or chronic kidney disease. The purpose of this study was to investigate the effectiveness and safety of OAC in this high-risk, very elderly group. We used the Taiwan National Health Insurance Research Database to identify high-risk, very elderly subjects taking OAC, either warfarin or a non-vitamin K antagonist oral anticoagulant (NOAC), and compared them to non-OAC users for the composite net clinical endpoint of ischemic stroke, ICH, major bleeding, or mortality. We studied 7362 subjects (mean age 92.5 years), of whom 1737 were taking NOACs, 670 warfarin, and 4955 non-OACs. Compared to non-OACs, warfarin was associated with a higher risk of the composite endpoint (adjusted hazard ratio [aHR] 1.163; 95% confidence interval [CI] 1.052-1.287), whereas NOACs were associated with a lower risk (aHR 0.763; 95% CI 0.702-0.830). After propensity matching, NOACs were associated with a lower risk of events compared to non-OACs or warfarin, whereas warfarin had a similar risk compared to non-OACs. Warfarin was associated with a similar or even higher risk of composite clinical outcomes compared to non-OACs. NOACs were associated with a lower risk of composite endpoint compared to warfarin or non-OACs, and their use still should be considered in these high-risk, very elderly AF patients.

Clinical outcomes according to dose reduction criteria of apixaban in Japanese elderly patients with atrial fibrillation: J-ELD AF Registry subanalysis.

Dose reduction of apixaban is applied in atrial fibrillation (AF) patients fulfilling ≥ 2 of the following criteria: (1) age ≥ 80years, (2) body weight ≤ 60kg and (3) serum creatinine ≥ 1.5mg/dL. However, the clinical significance of each criterion remains unclear. The J-ELD AF Registry is a prospective observational study of elderly (≥ 75years) Japanese AF patients receiving on-label dose of apixaban. In patients receiving the standard dose (5mg bid, n = 1243), the incidence rates (% per patient-year) of stroke or systemic embolism in those fulfilling none [n = 516] or one of the above criteria (1) [n = 328], (2) [n = 378] and (3) [n = 21] were 1.24, 2.32, 1.41 and 4.93 (log-rank P = 0.422), respectively, and those of bleeding requiring hospitalization were 1.03, 0.99, 1.98 and 4.93 (P = 0.318), respectively. In patients receiving a reduced dose (2.5mg bid, n = 1,515), the incidences of stroke or systemic embolism in those fulfilling (1)/(2) [n = 1,331], (1)/(3) [n = 65], (2)/(3) [n = 23] and all three criteria [n = 96] were 1.38, 1.64, 4.67 and 3.51 (P = 0.295), respectively, and those of bleeding requiring hospitalization were 2.04, 1.64, 0.00 and 4.71 (P = 0.318), respectively. Univariate analysis demonstrated that the types or combinations of each criterion was not significantly associated with the incidence of thromboembolic or bleeding events. The types or combinations of the three apixaban dose reduction criteria did not have significant impact on effectiveness and safety in Japanese elderly AF patients receiving on-label dose of apixaban, although the impact of the creatinine criterion remains uncertain due to the few number of the patients.

Association Between Motor and Cognitive Performances in Elderly With Atrial Fibrillation: Strat-AF Study.

Background/Objective: Growing evidence suggests a close relationship between motor and cognitive abilities, but possible common underlying mechanisms are not well-established. Atrial fibrillation (AF) is associated with reduced physical performance and increased risk of cognitive decline. The study aimed to assess in a cohort of elderly AF patients: (1) the association between motor and cognitive performances, and (2) the influence and potential mediating role of cerebral lesions burden.Design: Strat-AF is a prospective, observational study investigating biological markers for cerebral bleeding risk stratification in AF patients on oral anticoagulants. Baseline cross-sectional data are presented here.Setting: Thrombosis outpatient clinic (Careggi University Hospital).Participants: One-hundred and seventy patients (mean age 77.7 ± 6.8; females 35%).Measurements: Baseline protocol included: neuropsychological battery, motor assessment [Short Physical Performance Battery (SPPB), and walking speed], and brain magnetic resonance imaging (MRI) used for the visual assessment of white matter hyperintensities, lacunar and non-lacunar infarcts, cerebral microbleeds, and global cortical and medial temporal atrophies.Results: Mean Montreal Cognitive Assessment (MoCA) total score was 21.9 ± 3.9, SPPB total score 9.5 ± 2.2, and walking speed 0.9 ± 0.2. In univariate analyses, both SPPB and walking speed were significantly associated with MoCA (r = 0.359, r = 0.372, respectively), visual search (r = 0.361, r = 0.322), Stroop (r = −0.272, r = −0.263), short story (r = 0.263, r = 0.310), and semantic fluency (r = 0.311, r = 0.360). In multivariate models adjusted for demographics, heart failure, physical activity, and either stroke history (Model 1) or neuroimaging markers (Model 2), both SPPB and walking speed were confirmed significantly associated with MoCA (Model 1: β = 0.256, β = 0.236; Model 2: β = 0.276, β = 0.272, respectively), visual search (Model 1: β = 0.350, β = 0.313; Model 2: β = 0.344, β = 0.307), semantic fluency (Model 1: β = 0.223, β = 0.261), and short story (Model 2: β = 0.245, β = 0.273).Conclusions: In our cohort of elderly AF patients, a direct association between motor and cognitive functions consistently recurred using different evaluation of the performances, without an evident mediating role of cerebral lesions burden.

Current status of proton pump inhibitor use in Japanese elderly patients with non-valvular atrial fibrillation: A subanalysis of the ANAFIE Registry.

The real-world status of proton pump inhibitor (PPI) use in patients with atrial fibrillation (AF) receiving antithrombotic treatment is largely unknown. The All Nippon AF In the Elderly (ANAFIE) Registry, a prospective, multicenter, observational study, aimed to determine treatment patterns, risk factors, and outcomes among elderly (aged ≥75 years) Japanese non-valvular AF (NVAF) patients in the real-world clinical setting. The present subanalysis of the ANAFIE Registry determined the PPI prescription status of 32,490 elderly Japanese NVAF patients. Patients were stratified by PPI use (PPI+) or no PPI use (PPI−). Risk scores for stroke (CHADS2, CHA2DS2-VASc) and bleeding (HAS-BLED), anticoagulant use, time in therapeutic range (TTR) for warfarin, and anticoagulant/antiplatelet combination use were evaluated. PPIs were used in 11,981 (36.9%) patients. Compared with the PPI− group, the PPI+ group included a greater proportion of female patients (45.2% vs 41.3%; P <0.0001) and had significantly higher CHADS2, CHA2DS2-VASc, and HAS-BLED scores (P <0.0001 for each) as well as higher prevalences of several comorbidities. In the PPI+ group, 54.6% of patients did not have gastrointestinal (GI) disorders and were likely prescribed a PPI to prevent GI bleeding events. Most of the patients with a GI disorder in the PPI+ group had reflux esophagitis. Compared with patients not receiving anticoagulants, a significantly higher proportion of patients receiving anticoagulants received PPIs. For patients receiving anticoagulants, antiplatelet drugs, and both drugs, rates of PPI use were 34.1%, 44.1%, and 53.5%, respectively (P <0.01). Although the rate of PPI use was the highest for NVAF patients receiving both antiplatelet and anticoagulants, no clear differences were observed in the anticoagulants used. These data suggest that PPIs were actively prescribed in high-risk cases and may have been used to prevent GI bleeding among elderly NVAF patients receiving antithrombotic drugs.Trial registration: UMIN000024006

Risk factors associated with stroke/systemic embolic events in elderly non-valvular atrial fibrillation patients in the ANAFIE registry, the largest real-world elderly AF registry

Abstract Background Since prevalence of atrial fibrillation (AF) is increasing by aging, AF in elderly has been recognized as a big burden to keep long lasting healthy life worldwide. CHADS2 and CHA2DS2-VASc scores are commonly used for stroke risk assessment for AF, but predictors for elderly was not well elucidated, especially for very elderly (≥85 years old) patients. Purpose All Nippon AF In the Elderly (ANAFIE) registry was designed to evaluate a real-world treatment status of elderly (≥75 years old) non-valvular AF (NVAF) patients, including anticoagulant therapy and outcomes. The present analysis aimed to identify factors for stroke/systemic embolic events (SEE) of elderly NVAF patients using the dataset of ANAFIE registry, which was 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 of stroke/SEE for total population, &amp;lt;85 years old group and ≥85 years old group was estimated using Kaplan-Meier method. Cox proportional hazards model was used to determine independent predictors of stroke/SEE. The factors included in the model were selected by backward elimination procedure. Results Mean age was 81.5 years. 23,738 (74%) was &amp;lt;85 years old and 8,361 (26%) was ≥85 years old. Women were more prevalent in ≥85 years old than in &amp;lt;85 years old group (53.2 vs 39.0%). Mean CHADS2 and CHA2DS2-VASc scores in the ≥85 years group were 3.0 and 4.7, and 2.8 and 4.4 in the &amp;lt;85 years group, respectively. 92.5% of whole population used anti-coagulants including warfarin (27.6%) or direct oral anticoagulants (DOACs) (72.3%). Stroke/SEE occurred in 396 patients at 12 month with 256 in &amp;lt;85 years old and 140 in ≥85 years old group. The cumulative incidence rate of stroke/SEE by Kaplan-Meier method at 12 months was 1.2% in the whole patients, and was higher in ≥85 years than in &amp;lt;85 years old group (1.7% vs 1.1%). In the multivariate analysis using the whole patients, age ≥85 years (hazard ratio [HR]: 1.27), history of major bleeding (HR: 1.93), persistent AF (HR: 1.64), longstanding persistent and permanent AF (HR: 1.61), high systolic blood pressure (130-&amp;lt;140 [HR: 1.43], ≥140 [HR: 1.44]), prior stroke (HR: 2.09), dementia (HR: 1.34), creatinine clearance &amp;lt;30 mL/min (HR: 1.82) emerged as independent predictors. Independent predictors for stroke/SEE were almost similar between &amp;lt;85 and ≥85 years old group except hypertension and diabetes. High blood pressure was associated with stroke/SEE only in patients aged &amp;lt;85 years, and high blood sugar was only associated in patients aged ≥85 years. Conclusion Among elderly NVAF patients in the era of DOACs, higher age (≥85 years), type of AF, prior major bleeding, high blood pressure, prior stroke, dementia, and low creatinine clearance were identified as independent predictors of stroke/SEE. The blood pressure and blood sugar control differently affected &amp;lt;85 years vs ≥85 years old group. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Daiichi Sankyo Co., Ltd.

Thromboembolic events and major bleeding in frail patients with incident atrial fibrillation: a nationwide cohort study

Abstract Background Growing evidence suggests that frail patients presenting with atrial fibrillation (AF) are less likely to receive adequate oral anticoagulant therapy (OAC) despite high thromboembolic risk. There is a paucity of evidence investigating clinical outcomes in different antithrombotic strategies. Purpose To assess thromboembolic events, bleeding, and all-cause mortality according to OAC treatment regimen in a Danish nationwide cohort of frail patients with AF Method We included all patients with non-valvular AF between 2011 and 2018 who were aged ≥64 years and had a frailty risk score &amp;gt;5 according to the ICD-10 based Hospital Frailty Risk Score. Patients with an OAC indication other than atrial fibrillation were excluded. The cohort was stratified by treatment regimen: warfarin, NOACs standard dose, NOACs reduced dose, or no OAC, determined by treatment status within 60 days before and 30 days after AF diagnosis. Patients were followed from 30 days after AF diagnosis (index date) for the occurrence of thromboembolic events and major bleeding. Cumulative incidence functions were used to depict development of outcome risk over time using on the Aalen–Johansen estimator assuming death as competing risk. Results We identified 31,745 frail AF patients (mean age 80.7 years, 53.8% female); 16540 (52.1%) received no OAC, 2993 (9.4%) received warfarin, 6181 (19.5%) received standard dose NOACs, and 6031 (19.0%) revived reduced dose NOACs. Risk of developing the outcomes over time is depicted in Figure 1. At 1-year follow-up, the absolute risk of thromboembolic events was 5.0% for patients with no OAC, 4.2% for reduced dose NOACs, 4.1% for warfarin, and 3.4% for standard dose NOACs. Bleeding risk was 6.1% for warfarin, 5.4% for reduced dose NOACs, 5.2% for No OAC, and 5.1% for standard dose NOACs. Conclusions Most patients in this nationwide cohort of elderly frail AF patients received no OAC, which was associated with a high risk of thromboembolism. The associated risk of thromboembolism was lower in patients receiving other studied treatment modalities, which might suggest a benefit of OAC across different antithrombotic strategies in frail AF patients. However, differences in risk profile and patient specific factors are likely to influence our observations, and studies investigating the comparative effectiveness and safety of NOACs including dosage regimens in frail AF patients are warranted. Figure 1. Cumulative risk of events Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Bayer AG

Real-world effectiveness and the safety of anticoagulant treatment in elderly non-valvular atrial fibrillation in the ANAFIE registry, the largest real-world elderly AF registry

Abstract Background The optimal anticoagulant regimen for elderly AF has not been well elucidated, because this population, especially the very elderly (≥85 years), have not been sufficiently represented in most randomized controlled clinical trials for stroke prevention in non-valvular AF (NVAF). Purpose The ANAFIE registry was designed to evaluate the real-world anticoagulant treatment status of elderly (≥75 years) NVAF patients including &amp;gt;8,000 very elderly patients. In this main analysis of the ANAFIE, the incidence of stroke or systemic embolic events (stroke/SEE), and major bleeding were compared between warfarin (WF) and direct oral anticoagulants (DOACs). Methods A total of 33,018 NVAF patients aged ≥75 years was enrolled in the ANAFIE, and followed for 2 years. The incidence of stroke/SEE and major bleeding by type of anticoagulants (WF and all DOACs) was estimated using Kaplan-Meier method. Hazard ratio (HR) and 95% confidence interval (95% CI) were calculated by Cox proportional hazard model. Results In the analysis set of 32,099 patients, the mean age was 81.5 years. 23,738 (74%) were &amp;lt;85 years and 8,361 (26.0%) were ≥85 years. 92.5% of the whole population used anticoagulants including WF (27.6%) or DOACs (72.3%). The ratio of each DOAC was dabigatran 7.8%, rivaroxaban 21.5%, apixaban 26.9% and edoxaban 16.1%. Stroke/SEE and major bleeding was observed in 396 patients (1.24/100 patient-years [py]) and 279 patients (0.87/100py). The time in therapeutic range for patients &amp;lt;85 years and ≥85 years in the WF group was 76.7% and 72.2%, respectively. The incidence of stroke/SEE was numerically lower in patients taking any DOAC vs. WF regardless of age group (&amp;lt;85 years [HR 0.83] and ≥85 years [HR 0.71]). Major bleeding was also lower vs. WF in both age groups (&amp;lt;85 years [HR 0.60] and ≥85 years [HR 0.65]). Conclusion In elderly NVAF patients enrolled in the ANAFIE registry, the incidence of stroke/SEE and major bleeding was lower in patients taking a DOAC compared with WF for all patients ≥75 years, even for very elderly patients. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Daiichi Sankyo Co., Ltd.

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

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, &amp;lt;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 &amp;lt;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 &amp;lt;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 &amp;lt;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 &amp;lt;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 &amp;lt;30 mL/min (HR: 1.53) and polypharmacy (HR: 1.61) were associated with major bleeding only in those aged &amp;lt;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 (&amp;lt;85 years vs ≥85 years). Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Daiichi Sankyo Co., Ltd.

Edoxaban treatment of elderly patients with atrial fibrillation in routine clinical practice: 1-year results of the non-interventional Global ETNA-AF program

Abstract Background The prevalence of atrial fibrillation (AF) and the need for appropriate anticoagulation increase with age. The benefit/risk profile of direct oral anticoagulants such as edoxaban in elderly population with AF in regular clinical practice is therefore of particular interest. Purpose Analyses of Global ETNA-AF data were performed to report patient characteristics, edoxaban treatment, and 1-year clinical events by age subgroups. Methods Global ETNA-AF is a multicentre, prospective, noninterventional program conducted in Europe, Japan, Korea, Taiwan, and other Asian countries. Demographics, baseline characteristics, and 1-year clinical event data were analysed in four age subgroups. Results Of 26,823 patients included in this analysis, 50.4% were ≥75 years old and 11.6% were ≥85 years. Increase in age was generally associated with lower body weight, lower creatinine clearance, higher CHA2DS2-VASc and HAS-BLED scores, and a higher percentage of patients receiving the reduced dose of 30 mg daily edoxaban. At 1-year, rates of ISTH major bleeding and ischaemic stroke were generally low across all age subgroups. The proportion of intracranial haemorrhage within major bleeding events was similar across age groups. All-cause mortality increased with age more than cardiovascular mortality. Conclusion Data from Global ETNA-AF support the safety and effectiveness of edoxaban in elderly AF patients (including ≥85 years) in routine clinical care with only a small increase in intracranial haemorrhage. The higher all-cause mortality with increasing age is not driven by cardiovascular causes. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Daiichi Sankyo

Oral anticoagulants in extremely high risk very elderly (&amp;gt;90 years) patients with Atrial Fibrillation

Abstract Background The prevalence and incidence of atrial fibrillation (AF) increases with age, resulting in a high mortality and morbidity, especially from stroke and systemic thromboembolism (SSE). Nonetheless, the elderly are often denied oral anticoagulants (OACs), especially if they are “very elderly” (age ≥90 years) and perceived to be “high risk” of bleeding, for example, those with a history of intracranial haemorrhage (ICH), gastrointestinal bleeding or chronic kidney disease. We aimed to investigate the effectiveness and safety of OAC in this “high risk” very elderly group. Methods We used the Taiwan National Insurance Database to identify “high risk” very elderly subjects taking OACs, whether warfarin or non-vitamin K antagonist OACs (NOACs), who were compared to non-OAC users for the composite clinical endpoint of “ischemic stroke, ICH, major bleeding or mortality”. Propensity score matching was used for comparisons of the treatment groups. Results We studied 7,362 subjects (48.4% males; mean age 92.5 years, SD 2.78), of which 1737 were taking NOACs, 670 warfarin and 4955 were non-OAC users. Using non-OAC users as the reference group, warfarin use in “high risk” very elderly patients was associated with a higher risk of the composite endpoint (adjusted hazard ratio [aHR] 1.163, 95% CI 1.052–1.287), while NOACs were associated with a lower risk (aHR 0.763, 0.702–0.830). After propensity matching, NOACs were associated with a lower risk of events compared to “non-OAC use” or “warfarin”, while warfarin had a similar risk compared to non-OAC use (Figure). Conclusions Warfarin was associated with a similar (after propensity matching) or higher (Cox model before matching) risk of the composite clinical outcome compared to non-OAC use. NOACs were associated with a significantly lower risk of the composite clinical outcome compared to warfarin or non-OAC use. NOACs should be considered as the preferred OAC strategy in these “high risk” very elderly AF patients. Funding Acknowledgement Type of funding source: None

Oral Anticoagulant Use in Elderly Japanese Patients With Non-Valvular Atrial Fibrillation - Subanalysis of the ANAFIE Registry.

Background: Oral anticoagulants (OACs) are effective in preventing stroke in patients with atrial fibrillation (AF), but are challenging for elderly patients because of the higher risk of bleeding complications.Methods and Results: The ANAFIE Registry is a prospective multicenter observational study of elderly (≥75 years) Japanese AF patients. This subanalysis evaluated the current use of OACs. Of 32,713 patients (mean age 81.5 years), 30,068 (91.9%) were receiving OACs, including 8,354 (25.5%) on warfarin and 21,714 (66.4%) on direct OACs (DOACs); 2,645 (8.1%) were not receiving OACs. The most common prescribed dose was a reduced dose for all DOACs. A substantial proportion of patients receiving the reduced dose did not fulfill dose reduction criteria (underdosing): apixaban, 25.1%; rivaroxaban, 26.3%; and edoxaban, 13.7%. Some patients received a lower off-label dose rather than the reduced dose: apixaban, 5.9%; rivaroxaban, 0.3%; edoxaban, 5.3%; and dabigatran, 13.6%. In multivariate analyses, advanced age, history of hemorrhage, paroxysmal AF, and antiplatelet drug use were significantly associated with no OAC. Advanced age, persistent or permanent AF, chronic kidney disease, and concomitant antiplatelet drugs were associated with warfarin rather than DOAC use.Conclusions: In the ANAFIE Registry, >90% of elderly Japanese AF patients received OAC therapy, mostly DOACs. Inappropriate low doses of DOACs that did not fulfill dose reduction criteria were prescribed in 20–30% of patients.

Cause of Death and Associated Factors in Elderly Patients With Atrial Fibrillation - Long-Term Retrospective Study.

Background: Oral anticoagulant (OAC) therapy reduces the risk of stroke in patients with atrial fibrillation (AF). This study elucidated the causes of death and related factors in elderly Japanese AF patients.Methods and Results: Over a median (interquartile range [IQR]) follow-up period of 46 (20–76) months, there were 171 all-cause deaths (28% cardiovascular, 46% non-cardiovascular, and 26% unknown causes) among 389 AF patients (median [IQR] age 80 [74–85] years; CHAD2DS2-VASc score 5 [4–6]). Cox regression analysis indicated that diabetes was associated with an increase in all-cause death (hazard ratio [HR] 1.48; 95% confidence interval [CI] 1.02–2.13), whereas hypercholesterolemia (HR 0.53; 95% CI 0.35–0.79), pre-existing heart failure (HR 0.67; 95% CI 0.48–0.95), and OAC use (HR 0.62; 95% CI 0.44–0.88) were associated with reductions in all-cause death. Pre-existing heart failure was associated with both cardiovascular (HR 3.03; 95% CI 1.33–8.20) and non-cardiovascular (HR 0.44; 95% CI 0.30–0.65) deaths, in opposite directions. OAC use was associated with a reduction in cardiovascular death (HR 0.34, 95% CI 0.17–0.69). The predominance of non-cardiovascular death and death-related factors were equivalent regardless of when observations started (before 2009 or in 2009 and later).Conclusions: The predominant cause of death in elderly Japanese AF patients was non-cardiovascular. Distinct clinical factors were associated with cardiovascular and non-cardiovascular death.

Novel oral anticoagulant vs. warfarin in elderly atrial fibrillation patients with normal, mid-range, and reduced left ventricular ejection fraction.

AimsPatients with concomitant atrial fibrillation (AF) and reduced left ventricular ejection fraction (LVEF) have poor prognosis. Outcomes of novel oral anticoagulant (NOAC) in elderly AF patients with normal, mid‐range, and reduced LVEF were investigated.Methods and resultsData were retrieved from Chang Gung Research Database during 2010–2017 for patients with AF. We excluded patients with venous thromboembolism within 6 months, total knee/hip replacement and heart valve replacement within 6 months, end‐stage renal disease, stroke/systemic embolism (SE)/death within 7 days, age <65 years old, or no records of LVEF. Primary outcomes were ischaemic stroke (IS)/SE, major bleeding, and death from any cause. There was a total of 50 035 elderly AF patients retrieved. After exclusion criteria, 9615 patients with normal LVEF ≥ 50%, 737 with mid‐range LVEF 41–49%, and 908 with reduced LVEF ≤ 40% were studied. At end of follow‐up, patients on NOAC had significantly reduced IS/SE compared with warfarin in LVEF ≥ 50% [adjusted hazard ration (aHR) 0.80, 95% confidence interval (CI) 0.71–0.89] and LVEF 41–49% (aHR 0.57, 95% CI 0.36–0.88) after adjusting for covariates, while there was no difference in LVEF ≤ 40%. Patients on NOAC had significantly reduced major bleeding in all LVEF groups. In addition, patients on NOAC had significantly reduced death compared with warfarin in LVEF ≥ 50% (aHR 0.81, 95% CI 0.67–0.98).ConclusionsIn elderly AF patients ≥65 years, using NOAC was associated with lower IS/SE compared with warfarin in normal and mid‐range LVEF but not in reduced LVEF. Using NOACs was associated with lower death compared with warfarin in normal LVEF.

Differences in treatment and prognosis by the experience of falls or bone fracture in elderly patients with atrial fibrillation.

Treatment and prognosis of elderly patients with atrial fibrillation (AF) may differ by the experience of fall or bone fracture. However, their current status is still unclear. From our institute database between 2010 and 2015, 674 AF patients with age ≥ 70years were selected and were divided into those who experienced fall or fracture during the observation period (F/F group; n = 49) and those who did not (non-F/F group; n = 625). We compared the treatment and prognosis between the 2 groups. Patients in the F/F group were older (79 vs 76years, P < 0.001) and had more comorbidities compared with those in the non-F/F group. The prescription rate of oral anticoagulant was similar between the two groups (77.6% vs 68.2%, P = 0.201), where warfarin was predominant. The F/F group was not associated with higher incidence of ischemic stroke. The F/F group was associated with a higher incidence of heart failure events (adjusted odds ratio (OR) 3.88; 95% confidence intervals (Cl) 1.70-8.85; P = 0.001), and cardiovascular events (OR 3.43; 95% Cl 1.71-6.85; P < 0.001). In elderly AF patients in a cardiovascular hospital, the experience of fall or fracture did not affect the prescription of oral anticoagulants and the incidence of ischemic stroke, but it was significantly associated with increase of heart failure.

Abstract P369: Polypharmacy, Adverse Outcomes, and Treatment Effectiveness in Elderly Patients With Atrial Fibrillation

Background: Polypharmacy is highly prevalent in elderly individuals with chronic conditions, including atrial fibrillation (AF). The impact of polypharmacy on adverse outcomes and on treatment effectiveness in elderly AF patients remains unaddressed. Methods: We studied 338,810 AF patients ≥75 years of age with 1,761,660 active prescriptions [mean (SD), 5.1 (3.8) per patient] enrolled in the MarketScan Medicare Supplemental database in 2007-2015. Polypharmacy was defined as ≥5 active prescriptions at AF diagnosis based on outpatient pharmacy claims. AF treatments (oral anticoagulation, rhythm and rate control) and cardiovascular endpoints (ischemic stroke, bleeding, heart failure) were defined based on inpatient, outpatient and pharmacy claims. Multivariable Cox models were used to estimate associations of polypharmacy with cardiovascular endpoints and the interaction between polypharmacy and AF treatments in relation to cardiovascular endpoints. Results: Prevalence of polypharmacy was 52% (176,007 of 338,810). Patients with polypharmacy had increased risk of major bleeding [hazard ratio (HR) 1.16, 95% confidence interval (CI) 1.12, 1.20] and heart failure (HR 1.33, 95%CI 1.29, 1.36), but not of ischemic stroke (HR 0.96, 95%CI 0.92, 1.00), compared to those not with polypharmacy (Table). Polypharmacy status did not consistently modify the effectiveness of oral anticoagulants. However, rhythm control (vs. rate control) was more effective in preventing heart failure hospitalization in patients not with polypharmacy (HR 0.87, 95%CI 0.76, 0.99) than among those with polypharmacy (HR 0.98, 95%CI 0.91, 1.07, p for interaction = 0.02). Conclusion: Polypharmacy is frequent among elderly patients with AF, associated with adverse outcomes, and potentially affecting the effectiveness of AF treatments. Optimizing management of polypharmacy in elderly AF patients may lead to improved outcomes.

Comparison of effectiveness and safety of direct oral anticoagulants versus vitamin-k antagonists in elderly patients with atrial fibrillation: a systematic review and cost-effectiveness analysis protocol.

BackgroundCurrent evidence regarding the effectiveness and safety of direct oral anticoagulants (DOACs) in the elderly with atrial fibrillation (AF) remains scarce. Based on the emerging evidence from real-world studies (RWSs) associated with DOACs, we will perform a systematic review and meta-analysis of data from RWSs and randomized controlled trials (RCTs) to compare the effectiveness, safety and cost of DOACs versus Vitamin K antagonists (VKAs) in elderly patients with AF.MethodsThe MEDLINE, EMBASE and Cochrane Library databases will be systematically searched until June 30, 2019 for eligible RWSs and RCTs that reported the clinical outcomes between DOACs and VKAs in elderly patients with AF. The effectiveness outcome is stroke or systemic embolism (SE), and the safety outcomes are major bleeding, intracranial haemorrhage (ICH), gastrointestinal bleeding (GIB), myocardial infarction (MI) and all-cause mortality. A random-effects model will be used to calculate adjusted hazard ratios (HRs) for RWSs and relative risks (RRs) for RCTs, separately. The interaction analysis and the ratio of HRs (RHRs) will be applied to compare the treatment effect difference between RWSs and RCTs. A Markov model will be constructed to evaluate the cost-effectiveness of DOACs versus VKAs in elderly AF patients in real-world setting.DiscussionThis study will summarize all available evidences from RWSs and RCTs for a comprehensive and rigorous systematic review on the effectiveness and safety associated with DOACs, as well as perform a cost-effectiveness analysis to evaluate the price performance of DOACs among elderly AF patients in real clinical setting.Trial registrationPROSPERO register platform (CRD42019142881, www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID =142881).

Integrated management of atrial fibrillation in primary care: results of the ALL-IN cluster randomized trial.

AimsTo evaluate whether integrated care for atrial fibrillation (AF) can be safely orchestrated in primary care.Methods and resultsThe ALL-IN trial was a cluster randomized, open-label, pragmatic non-inferiority trial performed in primary care practices in the Netherlands. We randomized 26 practices: 15 to the integrated care intervention and 11 to usual care. The integrated care intervention consisted of (i) quarterly AF check-ups by trained nurses in primary care, also focusing on possibly interfering comorbidities, (ii) monitoring of anticoagulation therapy in primary care, and finally (iii) easy-access availability of consultations from cardiologists and anticoagulation clinics. The primary endpoint was all-cause mortality during 2 years of follow-up. In the intervention arm, 527 out of 941 eligible AF patients aged ≥65 years provided informed consent to undergo the intervention. These 527 patients were compared with 713 AF patients in the control arm receiving usual care. Median age was 77 (interquartile range 72–83) years. The all-cause mortality rate was 3.5 per 100 patient-years in the intervention arm vs. 6.7 per 100 patient-years in the control arm [adjusted hazard ratio (HR) 0.55; 95% confidence interval (CI) 0.37–0.82]. For non-cardiovascular mortality, the adjusted HR was 0.47 (95% CI 0.27–0.82). For other adverse events, no statistically significant differences were observed.ConclusionIn this cluster randomized trial, integrated care for elderly AF patients in primary care showed a 45% reduction in all-cause mortality when compared with usual care.

Prevalence and Associated Risk Factors of Cerebral Microbleeds in Egyptian Patients with Acute Ischemic Stroke and Atrial Fibrillation

BackgroundFew studies addressed the prevalence of cerebral microbleeds (CMB) and associated risk factor profile in Egyptian ischemic cerebral stroke patients with atrial fibrillation (AF). MethodsThe prevalence of CMB was estimated in 150 cases of AF ischemic stroke patients and compared to the prevalence in 150 age- and sex-matched controls of ischemic stroke patients without AF. CMB-associated risk factors were identified by comparing AF ischemic stroke patients with and without CMB. All participants were subjected to complete general, neurological examination, and magnetic resonance imaging. ResultsThe prevalence of CMBs in ischemic stroke with and without AF was 40.7% and 49.3%, respectively. Age, hypertension, diabetes mellitus, past history of stroke, antiplatelet, anticoagulant, National Institutes of Health Stroke Scale, CHA2DS2VASc, and white matter lesions (WML) were significant risk factors associated with CMB on univariate analysis. On multivariable logistic regression analysis, age (odds ratio [OR] 1.1, confidence interval [CI] 1.02-1.13), hypertension (OR 3.2, CI 1.19-8.81), anticoagulant (OR 3.3, CI 1.17-9.40), and WML (OR 9.6, CI 3.49-26.3) were the only independent risk factors associated with the presence of CMBs. ConclusionsAF in ischemic stroke patients was not associated with higher prevalence of CMBs. Old age, hypertension, anticoagulant treatment, and WML were the independent risk factors associated with CMB in AF ischemic stroke patients. Our results suggest that elderly hypertensive AF ischemic stroke patients maintained on anticoagulant therapy should be screened for the incidence of CMBs and monitored regularly for the development of intracerebral hemorrhage.

Rhythm versus rate control strategies regarding anticoagulant use in elderly non-valvular atrial fibrillation patients: Subanalysis of the ANAFIE (All Nippon AF In the Elderly) Registry

BackgroundData on real-world antiarrhythmic and anticoagulant therapy use in elderly atrial fibrillation (AF) patients are lacking; thus, we performed a subanalysis of data from the ANAFIE registry to clarify the current management of Japanese patients aged ≥75 years with non-valvular AF. MethodsThe ANAFIE registry was a multicenter, prospective, observational study. Patients were stratified into three groups: rhythm control group, rate control group, and no antiarrhythmic group. The CHADS2, CHA2DS2-VASc, and HAS-BLED scores were used to estimate embolic and bleeding risk. ResultsAmong 32,490 patients, the overall frequencies of AF by type were 42.0 % (paroxysmal), 30.1 % (persistent and long-standing persistent), and 27.9 % (permanent). Significant differences (p < 0.0001, each) in age were observed among the three groups; more patients aged 75–79 years received rhythm control (44.2 %) vs rate control (38.8 %). Patients aged ≥85 years received either rate control therapy or no antiarrhythmic agent (∼20 %, each). In the overall population, 36.9 % and 19.6 % of patients were receiving rate and rhythm control therapy, respectively; 43.4 % were not receiving antiarrhythmic therapy. The rate control group consisted mainly of patients with persistent (16.3 %) and permanent AF (38.6 %), and the rhythm control group, of patients with paroxysmal AF (79.0 %). Significantly lower embolic and bleeding risk scores and significantly higher embolic risk scores were observed in patients in the rhythm and rate control groups, respectively. In total, 92.1 % of elderly Japanese patients with AF were receiving anticoagulant therapy. The frequency of direct-acting oral anticoagulant (DOAC) use was similar (∼66 %) among the three groups. Significantly more patients in the rate control group (28.6 %) were being treated with warfarin than in the rhythm control group (21.6 %) (p < 0.0001). ConclusionsUse versus non-use and antiarrhythmic therapy varied significantly by age, stroke risk scores, type of AF, and DOAC use between subgroups.

Clinical Factors Associated with a Successful Catheter Ablation Outcome in Elderly Patients with Atrial Fibrillation.

Catheter ablation is currently an established treatment for symptomatic paroxysmal atrial fibrillation (AF). We focused on elderly patients with a high prevalence of AF and attempted to identify the clinical factors associated with unsuccessful ablation outcomes.Among 735 consecutive patients who underwent AF ablation procedures, 108 (14.7%, 66 men) aged ≥ 75 years were included. Of them, 80 had paroxysmal AF, and the remaining 28 non-paroxysmal AF. All patients underwent pulmonary vein (PV) isolation and occasionally additional ablation. When AF recurred, redo ablation procedures were performed if the patient so desired.The mean number of ablation procedures was 1.1 ± 0.4 times per patient. During a mean follow-up of 38.7 ± 21.7 months, sinus rhythm was maintained in 100 patients (92.6%) without any antiarrhythmic drugs, but not in the remaining 8 (7.4%). Left atrial diameter (LAD, P < 0.001), left ventricular (LV) systolic diameter (P < 0.001), LV diastolic diameter (P = 0.001), non-PV AF foci (P = 0.036), and diabetes (P = 0.045) were associated with unsuccessful ablation procedures. Multivariate logistic regression analysis revealed a large LAD and non-PV AF foci were significant independent predictors of AF recurrences, with odds ratios of 0.76 (P = 0.019) and 0.04 (P = 0.023), respectively. In a total of 124 procedures, one major (0.8%) and 11 minor (8.9%) complications occurred.In elderly AF patients, catheter ablation of AF is effective and safe. Non-PV AF foci and a large LAD were independent clinical predictors of unsuccessful AF ablation outcomes.