Educational status and the risk of adverse outcomes in Asian patients with atrial fibrillation: a report from the prospective APHRS-AF Registry.

BACKGROUND: The aim of this study was to evaluate the impact of educational status (ES) on the clinical course of Asian patients with atrial fibrillation (AF). METHODS: We used data from the prospective APHRS-AF Registry. ES was classified as follows: low (primary school), medium (secondary), and high (University). The primary outcome was a composite of all-cause death, thromboembolic events, acute coronary syndrome, and heart failure. Secondary outcomes were each component of the primary outcome, cardiovascular death, and major bleeding. The one-year risk of primary and secondary outcomes was assessed through Cox-regressions. Adherence to the Atrial fibrillation Better Care (ABC) pathway was assessed. RESULTS: Among 2697 AF patients (69±12 years, 34.8% females), 34.6% had low ES; 37.3% had medium ES; and 28.1% had high ES. Compared to patients with medium-high ES, patients with low ES were older, more often females, with a higher prevalence of cardiovascular risk factors, and a lower ABC pathway adherence (30.4% vs. 40.2%, P<0.001). On multivariable analysis, low ES was associated with a higher risk for the primary outcome (HR 1.52,95%CI 1.11-2.06) and all-cause death (HR 1.76,95%CI 1.10-2.83) than medium-high ES. A significant interaction was found for the risk of composite outcome among the different age strata, with the higher risk in the elderly (P for int=0.008), whereas the beneficial effect of the ABC pathway was irrespective of ES (P for int=0.691). CONCLUSIONS: In Asian AF patients, low ES is associated with high mortality. Efforts to improve education and include ES evaluation in the integrated care approach for AF are necessary to reduce the cardiovascular burden in these patients.

Signal-averaged electrocardiography as a noninvasive tool for evaluating the ventricular substrate in patients with nonischemic cardiomyopathy: reassessment of an old tool.

Introduction: Signal-averaged electrocardiography (SAECG) provides diagnostic and prognostic information regarding cardiac diseases. However, its value in other nonischemic cardiomyopathies (NICMs) remains unclear. This study aimed to investigate the role of SAECG in patients with NICM. Methods and results: This retrospective study included consecutive patients with NICM who underwent SAECG, biventricular substrate mapping, and ablation for ventricular arrhythmia (VA). Patients with baseline ventricular conduction disturbances were excluded. Patients who fulfilled at least one SAECG criterion were categorized into Group 1, and the other patients were categorized into Group 2. Baseline and ventricular substrate characteristics were compared between the two groups. The study included 58 patients (39 men, mean age 50.4 ± 15.5 years), with 34 and 24 patients in Groups 1 and 2, respectively. Epicardial mapping was performed in eight (23.5%) and six patients (25.0%) in Groups 1 and 2 (p = 0.897), respectively. Patients in Group 1 had a more extensive right ventricular (RV) low-voltage zone (LVZ) and scar area than those in Group 2. Group 1 had a larger epicardial LVZ than Group 2. Epicardial late potentials were more frequent in Group 1 than in Group 2. There were more arrhythmogenic foci within the RV outflow tract in Group 1 than in Group 2. There was no significant difference in long-term VA recurrence. Conclusion: In our NICM population, a positive SAECG was associated with a larger RV endocardial scar, epicardial scar/late potentials, and a higher incidence of arrhythmogenic foci in the RV outflow tract.

Patterns of comorbidities in patients with atrial fibrillation and impact on management and long-term prognosis: an analysis from the Prospective Global GLORIA-AF Registry.

BACKGROUND: Clinical complexity, as the interaction between ageing, frailty, multimorbidity and polypharmacy, is an increasing concern in patients with AF. There remains uncertainty regarding how combinations of comorbidities influence management and prognosis of patients with atrial fibrillation (AF). We aimed to identify phenotypes of AF patients according to comorbidities and to assess associations between comorbidity patterns, drug use and risk of major outcomes. METHODS: From the prospective GLORIA-AF Registry, we performed a latent class analysis based on 18 diseases, encompassing cardiovascular, metabolic, respiratory and other conditions; we then analysed the association between phenotypes of patients and (i) treatments received and (ii) the risk of major outcomes. Primary outcome was the composite of all-cause death and major adverse cardiovascular events (MACE). Secondary exploratory outcomes were also analysed. RESULTS: 32,560 AF patients (mean age 70.0 ± 10.5 years, 45.4% females) were included. We identified 6 phenotypes: (i) low complexity (39.2% of patients); (ii) cardiovascular (CV) risk factors (28.2%); (iii) atherosclerotic (10.2%); (iv) thromboembolic (8.1%); (v) cardiometabolic (7.6%) and (vi) high complexity (6.6%). Higher use of oral anticoagulants was found in more complex groups, with highest magnitude observed for the cardiometabolic and high complexity phenotypes (odds ratio and 95% confidence interval CI): 1.76 [1.49-2.09] and 1.57 [1.35-1.81], respectively); similar results were observed for beta-blockers and verapamil or diltiazem. We found higher risk of the primary outcome in all phenotypes, except the CV risk factor one, with highest risk observed for the cardiometabolic and high complexity groups (hazard ratio and 95%CI: 1.37 [1.13-1.67] and 1.47 [1.24-1.75], respectively). CONCLUSIONS: Comorbidities influence management and long-term prognosis of patients with AF. Patients with complex phenotypes may require comprehensive and holistic approaches to improve their prognosis.

Adverse Events and Clinical Correlates in Asian Patients with Atrial Fibrillation and Diabetes Mellitus: A Report from Asia Pacific Heart Rhythm Society Atrial Fibrillation Registry.

Aims. To evaluate the adverse events (and its clinical correlates) in a large prospective cohort of Asian patients with atrial fibrillation (AF) and diabetes mellitus (DM). Material and Methods. We recruited patients with atrial fibrillation (AF) from the Asia-Pacific Heart Rhythm Society (APHRS) AF Registry and included those for whom the diabetic mellitus (DM) status was known. We used Cox-regression analysis to assess the 1-year risk of all-cause death, thromboembolic events, acute coronary syndrome, heart failure and major bleeding. Results. Of 4058 patients (mean age 68.5 ± 11.8 years; 34.4% females) considered for this analysis, 999 (24.6%) had DM (age 71 ± 11 years, 36.4% females). Patients with DM had higher mean CHA2DS2-VASc (2.3 ± 1.6 vs. 4.0 ± 1.5, p < 0.001) and HAS-BLED (1.3 ± 1.0 vs. 1.7 ± 1.1, p < 0.001) risk scores and were less treated with rhythm control strategies compared to patients without DM (18.7% vs. 22.0%). After 1-year of follow-up, patients with DM had higher incidence of all-cause death (4.9% vs. 2.3%, p < 0.001), cardiovascular death (1.3% vs. 0.4%, p = 0.003), and major bleeding (1.8% vs. 0.9%, p = 0.002) compared to those without DM. On Cox regression analysis, adjusted for age, sex, heart failure, coronary and peripheral artery diseases and previous thromboembolic event, DM was independently associated with a higher risk of all-cause death (HR 1.48, 95% CI 1.00-2.19), cardiovascular death (HR 2.33, 95% CI 1.01-5.40), and major bleeding (HR 1.91, 95% 1.01-3.60). On interaction analysis, the impact of DM in determining the risk of all-cause death was greater in young than in older patients (p int = 0.010). Conclusions. Given the high rates of adverse outcomes in these Asian AF patients with DM, efforts to optimize the management approach of these high-risk patients in a holistic or integrated care approach are needed.

Initial eGFR Changes with SGLT2 Inhibitor in Patients With Type 2 Diabetes and Associations With the Risk of Abnormal Serum Potassium Level.

BACKGROUND: Both high and low levels of serum potassium measurements are linked with a higher risk of adverse clinical events among patients with type 2 diabetes. The study was aimed at evaluating the implications of the various degrees of initial estimated glomerular filtration rate (eGFR) change on subsequent serum potassium homeostasis following sodium-glucose cotransporter-2 inhibitor (SGLT2i) initiation among patients with type 2 diabetes. METHODS AND RESULTS: We used medical data from a multicenter health care provider in Taiwan and recruited 5529 patients with type 2 diabetes with baseline/follow-up eGFR data available after 4 to 12 weeks of SGLT2i treatment from June 1, 2016, to December 31, 2018. SGLT2i treatment was associated with an initial mean (SEM) eGFR decline of -3.5 (0.2) mL/min per 1.73 m2 in overall study participants. A total of 36.7% (n=2028) of patients experienced no eGFR decline, and 57.9% (n=3201) and 5.4% (n=300) of patients experienced an eGFR decline of 0% to 30% and >30%, respectively. Patients with an initial eGFR decline of >30% were associated with higher variability in consequent serum potassium measurement when compared with those without an initial eGFR decline. Participants with a pronounced eGFR decline of >30% were associated with a higher risk of hyperkalemia ≥5.5 (adjusted hazard ratio,4.59 [95% CI, 2.28-9.26]) or use of potassium binder (adjusted hazard ratio, 2.65 [95% CI, 1.78-3.95]) as well as hypokalemia events <3.0 mmol/L (adjusted hazard ratio, 3.21 [95% CI, 1.90-5.42]) or use of potassium supplement (adjusted hazard ratio, 1.87 [95% CI, 1.37-2.56]) following SGLT2i treatment after multivariate adjustment. CONCLUSIONS: Physicians should be aware that the eGFR trough occurs shortly, and consequent serum potassium changes following SGLT2i initiation.

SGLT2 inhibitors vs. GLP-1 receptor agonists and clinical outcomes in patients with diabetes with/without atrial fibrillation.

CONTEXT: The coexistence of diabetes mellitus and atrial fibrillation (AF) is associated with substantial risks of adverse cardiovascular events. OBJECTIVE: The relevant outcomes associated with the use of sodium-glucose cotransporter-2 inhibitor (SGLT2i) versus glucagon-like peptide-1 receptor agonists (GLP-1RA) among patients with type 2 diabetes (T2D) with/without concomitant AF remained unknown. METHODS: In this nationwide retrospective cohort study from Taiwan National Health Insurance Research Database, there were 344,392 and 31,351 patients with T2D without AF, and 11,462 and 816 T2D patients with AF treated with SGLT2i and GLP-1RA from May 1, 2016, to December 31, 2019. Patients were followed from the drug-index date until the occurrence of study events, discontinuation of the index drug, or the end of the study period (December 31, 2020), whichever occurred first. We used propensity score stabilized weight to balance covariates across two medication groups. RESULTS: The incidence rate of all study outcomes in patients with concomitant AF was much higher than in those without concomitant AF. For the AF cohort, SGLT2i vs. GLP-1RA was associated with a lower risk of hospitalization for heart failure (2.32 vs. 4.74 events per 100 person-years; hazard ratio (HR):0.48 [95% confidential interval (CI):0.36-0.66]), with no benefit seen for the non-AF cohort (P for homogeneity < 0.01). SGLT2i vs. GLP-1RA was associated with a lower risk of composite kidney outcomes both in the AF (0.38 vs. 0.79 events per 100 person-years; HR:0.47; [95%CI:0.23-0.96]) and non-AF cohorts (0.09 vs. 0.18 events per 100 person-years; HR:0.53; [95%CI:0.43-0.64]). There were no significant differences in the risk of major adverse cardiovascular events and all-cause mortality in those who received SGLT2i compared to GLP-1RA for the AF or non-AF cohorts. CONCLUSION: Considering the high risk of developing HF and/or high prevalence of concomitant HF in patients with diabetes, whether SGLT2i should be the preferred treatment to GLP-1RA for such a high-risk population requires further investigation.

The optimal antithrombotic strategy for post-stroke patients with atrial fibrillation and extracranial artery stenosis-a nationwide cohort study.

BACKGROUND: In post-stroke atrial fibrillation (AF) patients who have indications for both oral anticoagulant (OAC) and antiplatelet agent (AP), e.g., those with carotid artery stenosis, there is debate over the best antithrombotic strategy. We aimed to compare the risks of ischemic stroke, composite of ischemic stroke/major bleeding and composite of ischemic stroke/intracranial hemorrhage (ICH) between different antithrombotic strategies. METHODS: This study included post-stroke AF patients with and without extracranial artery stenosis (ECAS) (n = 6390 and 28,093, respectively) identified from the Taiwan National Health Insurance Research Database. Risks of clinical outcomes and net clinical benefit (NCB) with different antithrombotic strategies were compared to AP alone. RESULTS: The risk of recurrent ischemic stroke was higher for patients with ECAS than those without (12.72%/yr versus 10.60/yr; adjusted hazard ratio [aHR] 1.104, 95% confidence interval [CI] 1.052-1.158, p < 0.001). For patients with ECAS, when compared to AP only, non-vitamin K antagonist oral anticoagulant (NOAC) monotherapy was associated with lower risks for ischaemic stroke (aHR 0.551, 95% CI 0.454-0.669), the composite of ischaemic stroke/major bleeding (aHR 0.626, 95% CI 0.529-0.741) and the composite of ischaemic stroke/ICH (aHR 0.577, 95% CI 0.478-0.697), with non-significant difference for major bleeding and ICH. When compared to AP only, warfarin monotherapy was associated with higher risks of major bleeding (aHR 1.521, 95% CI 1.231-1.880), ICH (aHR 2.045, 95% CI 1.329-3.148), and the composite of ischaemic stroke and major bleeding. With combination of AP plus warfarin, there was an increase in ischaemic stroke, major bleeding, and the composite outcomes, when compared to AP only. NOAC monotherapy was the only approach associated with a positive NCB, while all other options (warfarin, combination of AP-OAC) were associated with negative NCB. CONCLUSIONS: For post-stroke AF patients with ECAS, NOAC monotherapy was associated with lower risks of adverse outcomes and a positive NCB. Combination of AP with NOAC or warfarin did not offer any benefit, but more bleeding especially with AP-warfarin combination therapy.

Risk of Death and Cardiovascular Events in Asian Patients With Atrial Fibrillation and Chronic Obstructive Pulmonary Disease: A Report From the Prospective APHRS Registry.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is associated with an increased risk of adverse events in patients with atrial fibrillation (AF); however, few data are available on this topic in Asian populations. METHODS AND RESULTS: Prospective observational study conducted on patients with AF enrolled in the Asia-Pacific Heart Rhythm Society (APHRS) AF Registry. The diagnosis of COPD was based on data reported in the case report form by the investigators. Cox-regression models were used to assess the 1-year risk of a primary composite outcome of all-cause death, thromboembolic events, acute coronary syndrome, and heart failure. Analysis on single outcomes and cardiovascular death was also performed. Interaction analysis was used to assess the risk of composite outcome and all-cause death in different subgroups. The study included 4094 patients with AF (mean±SD age 68.5±12 years, 34.6% female), of whom 112 (2.7%) had COPD. Patients with COPD showed a higher incidence of the primary composite outcome (25.1% versus 6.3%, P<0.001), all-cause death (14.9% versus 2.6%, P<0.001), cardiovascular death (2.0% versus 0.6%, P<0.001), and heart failure (8.3% versus 6.0%, P<0.001). On multiple Cox-regression analysis, COPD was associated with a higher risk of the primary composite outcome (hazard ratio [HR], 3.17 [95% CI, 2.05-4.90]), all-cause death (HR, 3.59 [95% CI, 2.04-6.30]), and heart failure (HR, 3.32 [95% CI, 1.56-7.03]); no statistically significant differences were found for other outcomes. The association between COPD and mortality was significantly modified by the use of beta blockers (Pint=0.018). CONCLUSIONS: In Asian patients with AF, COPD is associated with worse prognosis. In patients with AF and COPD, the use of beta blockers was associated with a lower mortality. REGISTRATION INFORMATION: clinicaltrials.gov Identifier: NCT04807049.

Predicting stroke in Asian patients with atrial fibrillation using machine learning: A report from the KERALA-AF registry, with external validation in the APHRS-AF registry.

Atrial fibrillation (AF) is a significant risk factor for stroke. Based on the higher stroke associated with AF in the South Asian population, we constructed a one-year stroke prediction model using machine learning (ML) methods in KERALA-AF South Asian cohort. External validation was performed in the prospective APHRS-AF registry. We studied 2101 patients and 83 were to patients with stroke in KERALA-AF registry. The random forest showed the best predictive performance in the internal validation with receiver operator characteristic curve (AUC) and G-mean of 0.821 and 0.427, respectively. In the external validation, the light gradient boosting machine showed the best predictive performance with AUC and G-mean of 0.670 and 0.083, respectively. We report the first demonstration of ML's applicability in an Indian prospective cohort, although the more modest prediction on external validation in a separate multinational Asian registry suggests the need for ethnic-specific ML models.

Atrial fibrillation: stroke prevention.

Stroke prevention is central to the management of patients with atrial fibrillation (AF) which has moved towards a more holistic or integrative care approach. The published evidence suggests that management of AF patients following such a holistic approach based on the Atrial fibrillation Better Care (ABC) pathway is associated with a lower risk of stroke and adverse events. Risk assessment, re-assessment and use of direct oral anticoagulants (DOACs) are important for stroke prevention in AF. The stroke and bleeding risks of AF patients are not static and should be re-assessed regularly. Bleeding risk assessment is to address and mitigate modifiable bleeding risk factors, and to identify high bleeding risk patients for early review and follow-up. Well-controlled comorbidities and healthy lifestyles also play an important role to achieve a better clinical outcome. Digital health solutions are increasingly relevant in the diagnosis and management of patients with AF, with the potential to improve stroke prevention. In this review, we provide an update on stroke prevention in AF, including importance of holistic management, risk assessment/re-assessment, and stroke prevention for special AF populations. Evidence-based and structured management of AF patients would reduce the risk of stroke and other adverse events.

Feasibility of Auto-Quantified Epicardial Adipose Tissue in Predicting Atrial Fibrillation Recurrence After Catheter Ablation.

BACKGROUND: The aim of this study was to build an auto-segmented artificial intelligence model of the atria and epicardial adipose tissue (EAT) on computed tomography (CT) images, and examine the prognostic significance of auto-quantified left atrium (LA) and EAT volumes for AF.Methods and Results: This retrospective study included 334 patients with AF who were referred for catheter ablation (CA) between 2015 and 2017. Atria and EAT volumes were auto-quantified using a pre-trained 3-dimensional (3D) U-Net model from pre-ablation CT images. After adjusting for factors associated with AF, Cox regression analysis was used to examine predictors of AF recurrence. The mean (±SD) age of patients was 56±11 years; 251 (75%) were men, and 79 (24%) had non-paroxysmal AF. Over 2 years of follow-up, 139 (42%) patients experienced recurrence. Diabetes, non-paroxysmal AF, non-pulmonary vein triggers, mitral line ablation, and larger LA, right atrium, and EAT volume indices were linked to increased hazards of AF recurrence. After multivariate adjustment, non-paroxysmal AF (hazard ratio [HR] 0.6; 95% confidence interval [CI] 0.4-0.8; P=0.003) and larger LA-EAT volume index (HR 1.1; 95% CI 1.0-1.2; P=0.009) remained independent predictors of AF recurrence. CONCLUSIONS: LA-EAT volume measured using the auto-quantified 3D U-Net model is feasible for predicting AF recurrence after CA, regardless of AF type.

Which dose of apixaban is suitable for Asian patients with atrial fibrillation who have a serum creatinine < 1.5 mg/dL but an estimated glomerular filtration rate < 50 mL/min?

Introduction: Reduced-dose (Low-dose [LD]) apixaban is recommended in patients with atrial fibrillation (AF) who fulfill 2 of 3 criteria: age ≥ 80 years, body weight ≤ 60 kg, and a serum creatinine (sCr) ≥ 1.5 mg/dl. However, the suitable (appropriate) dose for Asian patients who have a sCr < 1.5 mg/dl but an estimated glomerular filtration rate (eGFR) < 50 mL/min is unknown. Methods: This is a retrospective study using the Chang Gung Memorial hospital medical database in Taiwan. A total of 13,508 AF patients receiving oral anticoagulants (OACs) from 2012 to 2018 were reviewed and 1595 patients with a sCr < 1.5 mg/dL and an eGFR < 50 mL/min who met 1 criterion of dose reduction of apixaban other than sCr (that is, age ≥ 80 years or body weight < 60 kg) were identified. Clinical outcomes were compared between LD and SD apixaban versus warfarin. Results: Their OACs use was as follows: 343 receiving apixaban (128 patients on standard dose [SD] and 215 on LD), 174 receiving warfarin, and 1078 on other NOACs. Patients with an eGFR < 50 mL/min had higher risk of mortality (adjusted hazard ratio [aHR], 1.264; 95 % confidence interval [CI], 1.086-1.472) and composite endpoint of 'ischemic stroke/systemic embolism (IS/SE) or major bleeding or mortality (aHR, 1.202; 95 % CI, 1.056-1.370) compared to those with an eGFR ≥ 50 mL/min whereas the risk of IS/SE and major bleeding were similar. LD apixaban was associated with lower risk of composite endpoint of IS/SE or major bleeding (aHR, 0.567; 95 % CI, 0.331 - 0.972), mortality (aHR, 0.336; 95 % CI, 0.138 - 0.815), and 'IS/SE or major bleeding or mortality (aHR, 0.551; 95 % CI, 0343 - 0.886) compared to warfarin while the risk was comparable between SD apixaban and warfarin (aHR, 0.745; 95 % CI, 0.402 - 1.378; aHR, 0.407; 95 % CI, 0.145 - 1.143; aHR, 0.619; 95 % CI, 0.354 - 1.084, respectively). Conclusion: In patients with sCr < 1.5 mg/dL and eGFR < 50 mL/min, SD and LD apixaban were comparable in the prevention of IS/SE, but LD apixaban was superior in reducing the composite endpoint of 'IS/SE or major bleeding or mortality'. Therefore, LD apixaban might be a preferred dose for this population.

Use of artificial intelligence and I-Score for prediction of recurrence before catheter ablation of atrial fibrillation.

BACKGROUND: Based solely on pre-ablation characteristics, previous risk scores have demonstrated variable predictive performance. This study aimed to predict the recurrence of AF after catheter ablation by using artificial intelligence (AI)-enabled pre-ablation computed tomography (PVCT) images and pre-ablation clinical data. METHODS: A total of 638 drug-refractory paroxysmal atrial fibrillation (AF) patients undergone ablation were recruited. For model training, we used left atria (LA) acquired from pre-ablation PVCT slices (126,288 images). A total of 29 clinical variables were collected before ablation, including baseline characteristics, medical histories, laboratory results, transthoracic echocardiographic parameters, and 3D reconstructed LA volumes. The I-Score was applied to select variables for model training. For the prediction of one-year AF recurrence, PVCT deep-learning and clinical variable machine-learning models were developed. We then applied machine learning to ensemble the PVCT and clinical variable models. RESULTS: The PVCT model achieved an AUC of 0.63 in the test set. Various combinations of clinical variables selected by I-Score can yield an AUC of 0.72, which is significantly better than all variables or features selected by nonparametric statistics (AUCs of 0.66 to 0.69). The ensemble model (PVCT images and clinical variables) significantly improved predictive performance up to an AUC of 0.76 (sensitivity of 86.7% and specificity of 51.0%). CONCLUSIONS: Before ablation, AI-enabled PVCT combined with I-Score features was applicable in predicting recurrence in paroxysmal AF patients. Based on all possible predictors, the I-Score is capable of identifying the most influential combination.

External Validation of COOL-AF Scores in the Asian Pacific Heart Rhythm Society Atrial Fibrillation Registry.

Background: The COOL-AF (Cohort of Antithrombotic Use and Optimal International Normalized Ratio Levels in Patients with Atrial Fibrillation) risk scores for death, bleeding, and thromboembolic events (TEs) were derived from the COOL-AF cohort from Thailand and require external validation. Objectives: The authors sought to externally validate the COOL-AF scores in the APHRS (Asia-Pacific Heart Rhythm Society) registry and to compare their performance in the ESC-EHRA (European Society of Cardiology-European Heart Rhythm Association) EORP-AF (EURObservational Research Programme in Atrial Fibrillation) General Long-Term Registry. Methods: We studied 3,628 APHRS and 8,825 EORP-AF patients. Receiver operating characteristic (ROC) curves and Cox regression analyses were used to test the predictive value of COOL-AF scores and to compared them with the CHA2DS2-VASc and HAS-BLED scores. Results: Patients in the EORP-AF were older, had a higher prevalence of male sex, and were at higher thromboembolic and hemorrhagic risk than APHRS patients. After 1 year of follow-up in APHRS and EORP-AF, the following events were recorded: 87 (2.4%) and 435 (4.9%) death for any causes, 37 (1.0%) and 111 (1.3%) major bleeding, and 25 (0.7%) and 109 (1.2%) TEs, respectively. In APHRS, the COOL-AF scores showed moderate-to-good predictive value for all-cause mortality (area under the curve [AUC]: 0.77; 95% CI: 0.71-0.83), major bleeding (AUC: 0.68; 95% CI: 0.60-0.76), and TEs (AUC: 0.61; 95% CI: 0.51-0.71), and were similar to the CHA2DS2-VASc and HAS-BLED scores. In EORP-AF, the predictive value of COOL-AF for all-cause mortality (AUC: 0.68; 95% CI: 0.65-0.70) and major bleeding (AUC: 0.61; 95% CI: 0.60-0.62) was modest and lower than in APHRS. In EORP-AF, the COOL-AF score for TE was inferior to the CHA2DS2-VASc score. Conclusions: The COOL-AF risk scores may be an easy tool to identify Asian patients with AF at risk for death and major bleeding and performs better in Asian than in European patients with AF. (Clinical Survey on the Stroke Prevention in Atrial Fibrillation in Asia [AF-Registry]; NCT04807049).

Comparison of different direct oral anticoagulant regimens in atrial fibrillation patients with high bleeding risk.

BACKGROUND: The optimal dose of direct oral anticoagulants (DOACs) to prevent ischemic stroke (IS) and systemic thromboembolism (STE) in atrial fibrillation (AF) patients with a predisposing bleeding risk remains unclear. OBJECTIVE: The purpose of this study was to compare the effectiveness and safety of different DOAC dosage regimens in AF patients with high bleeding risk but low thrombosis risk. METHODS: This retrospective observational study was conducted with the National Health Insurance claims database in Taiwan to include AF patients aged 20 up to 75 years, under DOAC therapy, with CHA2DS2-VASc score of 1 for males and 2 for females and HAS-BLED score ≥3. Standard-dose regimen was defined as dabigatran 300 mg, rivaroxaban 20 mg, apixaban 10 mg, or edoxaban 60 mg per day. Any other lower-dose regimen were defined as the low-dose regimen. The primary outcomes were IS and major bleeding (MB). The secondary outcomes were STE, gastrointestinal bleeding, intracranial hemorrhage, and cardiovascular death. RESULTS: A total of 964 patients were included (52.1% standard-dose regimen). Median HAS-BLED score was 3 [interquartile range 3-3]. Compared with standard-dose group, patients in the low-dose group had a significantly increased risk of IS (adjusted hazard ratio [aHR] 5.13; 95% confidence interval 1.37-19.22) and STE (aHR 3.14 [1.05-9.37]) but similar risk of MB (aHR 0.45 [0.12-1.67]). The risks of other hemorrhage and cardiovascular death were similar between the 2 dose groups. CONCLUSION: Among patients with a predominant bleeding risk but relatively low thrombosis risk, the low-dose DOAC regimen is not a more appropriate selection than standard-dose regimen.

Cardiovascular and renal outcomes in patients with atrial fibrillation and stage 4-5 chronic kidney disease receiving direct oral anticoagulants: a multicenter retrospective cohort study.

The role of direct oral anticoagulants (DOAC) in patients with atrial fibrillation (AF) and stage 4-5 chronic kidney disease (CKD) is controversial. Electronic medical records from 2012 to 2021 were retrieved for patients with AF and stage 4-5 CKD receiving oral anticoagulants. Patients were separated into those receiving DOACs (dabigatran, rivaroxaban, apixaban, or edoxaban) or vitamin K antagonists (VKA). Primary outcomes included ischemic stroke (IS), systemic thrombosis (SE), major bleeding, gastrointestinal bleeding, hemorrhagic stroke, acute myocardial infarction, cardiovascular death, and all-cause death. Renal outcomes included eGFR declines, creatinine doubling, progression to dialysis, and major adverse kidney events (MAKE). The primary analysis was until the end of follow up and the results at 1-year and 2-year of follow ups were also assessed. 2,382 patients (DOAC = 1,047, VKA = 1,335) between 2012 and 2021 with AF and stage 4-5 CKD were identified. The mean follow-up period was 2.3 ± 2.1 years in DOCAs and 2.6 ± 2.3 years in VKA respectively. At the end of follow up, the DOAC patients had significantly decreased SE (subdistribution hazard ratio [SHR] = 0.50, 95% confidence interval [CI] = 0.34-0.73), composite of IS/SE (SHR = 0.78, 95% CI = 0.62-0.98), major bleeding (HR = 0.77, 95% CI = 0.66-0.90), hemorrhagic stroke (HR = 0.52, 95% CI = 0.36-0.76), and composite of bleeding events (SHR = 0.80, 95% CI = 0.69-0.92) compared with VKA patients. The IS efficacy outcome revealed neutral between DOAC and VKA patients (HR = 1.05, 95% CI = 0.79-1.39). In addition, DOAC patients had significantly decreased rates of eGFR decline > 50% (SHR = 0.75, 95% CI = 0.64-0.87), creatinine doubling (SHR = 0.80, 95% CI = 0.67-0.95), and MAKE (SHR = 0.81, 95% CI = 0.71-0.93). In patients with AF and stage 4-5 CKD, use of DOAC was associated with decreased rates of a composite of ischemic stroke/systemic embolism, a composite of bleeding events, and renal events compared to VKA. Efficacy and safety benefits associated with apixaban at standard doses were consistent throughout follow-up.

Risk of Incident Atrial Fibrillation and Subsequent Use of Oral Anticoagulants in Patients with Dementia.

BACKGROUND: Dementia and atrial fibrillation (AF) have many shared risk factors. Besides, patients with dementia are under-represented in randomized trials, and even if AF is present, oral anticoagulants (OACs) are not prescribed frequently. This study aimed to report the incidence of newly diagnosed AF in dementia patients, and the impacts of use of vitamin K antagonist (VKA; e.g., warfarin) and non-VKA OAC (NOACs) on stroke and bleeding outcomes. METHODS: Our study utilized the Taiwan National Health Insurance Research Database. A total of 554,074 patients with dementia were compared with 554,074 age- and sex-matched patients without dementia regarding the risk of incident AF. Among patients with dementia who experienced incident AF, the risks of clinical events of patients treated with warfarin or NOACs were compared with those without OACs (reference group). RESULTS: The risk of incident AF was greater for patients with dementia compared with those without (adjusted hazard ratio [aHR]: 1.054; 95% confidence interval [CI]: 1.040-1.068 for all types of dementia, aHR: 1.035; 95% CI: 1.020-1.051 for presenile/senile dementia, and aHR: 1.125; 95% CI: 1.091-1.159 for vascular dementia). Among patients with dementia and experienced incident AF, warfarin use was associated with a higher risk of ischemic stroke (aHR: 1.290; 95% CI: 1.156-1.440), intracranial hemorrhage (ICH; aHR: 1.678; 95% CI: 1.346-2.090), and major bleeding (aHR: 1.192; 95% CI: 1.073-1.323) compared with non-OACs. NOAC use was associated with a lower risk of ischemic stroke (aHR: 0.421; 95% CI: 0.352-0.503) and composite risk of ischemic stroke or major bleeding (aHR: 0.544; 95% CI: 0.487-0.608) compared with non-OACs. These results were consistent among the patients after the propensity matching. CONCLUSION: In this large nationwide cohort, the risk of newly diagnosed AF was higher in patients with dementia (all dementia, presenile/senile dementia, and vascular dementia) compared with those without dementia. For patients with dementia who experienced incident AF, NOAC use was associated with a better clinical outcome compared with non-OAC. Patients with dementia require a holistic approach to their care and management, including the use of NOACs to reduce the risks of clinical events.

The Report of Community-Based and Government-Endorsed Screening Program of Atrial Fibrillation in Taiwan.

BACKGROUND: Although international guidelines recommended opportunistic screening for atrial fibrillation (AF), the community-based AF screening program incorporated into the government-endorsed health care system is rarely reported in Asian countries. OBJECTIVES: We aimed to test the feasibility of adding AF screening into the preexistent adult health check program and report the AF detection rate and percentages of OAC prescriptions before and after AF screening with the involvement of public health care systems. METHODS: We performed this program in three counties (Chiayi county, Keelung City, and Yilan county) in Taiwan which have their own official preexistent adult health check programs conducted by public health bureaus for years. However, electrocardiography (ECG) was not included in these programs before. We cooperated with the public health bureaus of the three counties and performed single-lead 30-second ECG recording for every participant. RESULTS: From January to December 2020, AF screening was performed in 199 sessions with 23,572 participants. AF was detected in 278 subjects with a detection rate of 1.19% (age ≥65 years: 2.39%; ≥75 years: 3.73%). The mean CHA2DS2-VASc score of these 278 subjects was 2.36, with 91% of them had a score ≥1 (males) or ≥2 (females). The number needed to screen was 42 and 27 for subjects aged ≥65 and ≥75 years, respectively. The prescription rate of OACs significantly increased from 11.4 to 60.6% in Chiayi county and from 15.8 to 50.0% in Keelung City after screening (both p-values <0.001). CONCLUSION: This community-based and government-endorsed AF screening project in Taiwan demonstrated that incorporation of AF screening into the preexistent adult health check programs through co-operations with the government was feasible. Actions to detect AF, good education, and well-organized transferring plan after AF being detected with the involvement of public health care systems could result in a substantial increase in the prescription rate of OACs.