Purpose: Advanced chronic kidney disease (CKD), including end-stage renal disease (ESRD) on dialysis, increases thromboembolic risk among patients with atrial fibrillation (AF). This study examined the comparative safety and efficacy of direct-acting oral anticoagulant (DOAC) compared to warfarin or no oral anticoagulant (OAC) in AF patients with advanced CKD or ESRD on dialysis. Materials and Methods: Using data from the COmparison study of Drugs for symptom control and complication prEvention of AF (CODE-AF) registry, 260 non-valvular AF patients with advanced CKD (defined as estimated glomerular filtration rate <30 mL/min per 1.73/m2 ) or ESRD on dialysis were enrolled from June 2016 to July 2020. The study population was categorized into DOAC, warfarin, and no OAC groups; and differences in major or clinically relevant non-major (CRNM) bleeding, stroke/systemic embolism (SE), myocardial infarction/critical limb ischemia (CLI), and death were assessed. Results: During a median 24 months of follow-up, major or CRNM bleeding risk was significantly reduced in the DOAC group compared to the warfarin group [hazard ratio (HR) 0.11, 95% confidence interval (CI) 0.01 to 0.93, p=0.043]. In addition, the risk of composite adverse clinical outcomes (major or CRNM bleeding, stroke/SE, myocardial infarction/CLI, and death) was significantly reduced in the DOAC group compared to the no OAC group (HR 0.16, 95% CI 0.03 to 0.91, p=0.039). Conclusion Among AF patients with advanced CKD or ESRD on dialysis, DOAC was associated with a lower risk of major or CRNM bleeding compared to warfarin and a lower risk of composite adverse clinical outcomes compared to no OAC.ClinicalTrials.gov (NCT02786095)

Background: It has become important to identify and manage risk factors for subclinical atrial fibrillation (AF) with an increase in its detection rate. Thus, this research aimed to investigate whether alcohol consumption contrib‑ utes to the development of subclinical AF. Methods: This prospective study enrolled 467 patients without AF from a multicenter pacemaker registry. The incidence of subclinical AF (episodes of atrial rate > 220 beats per minute without symptoms) was compared between alcohol-drinking and non-drinking groups. Results: During followup (median 18 months), the incidence and risk of long-duration atrial high-rate episodes (AHRE) ≥ 24 h were increased in the alcohol group compared to the non-alcohol group [5.47 vs. 2.10 per 100 personyears, adjusted hazard ratio (HR), 2.83; 95% confidence interval (CI), 1.14–7.04; P = 0.03]. After propensity score match‑ ing, the incidence and risk of long-duration AHRE were higher in the alcohol group (6.97 vs. 1.27 per 100 personyears, adjusted HR, 7.84; 95% CI, 1.21–50.93; P = 0.03). The mean burden of long-duration subclinical AF was higher in the alcohol group than in the non-alcohol group (0.18 vs. 1.61% during follow-up, P = 0.08). Conclusion Alcohol consumption was associated with an increased risk of subclinical AF. Long-duration AHRE inci‑ dence and AHRE burden were higher in alcohol drinkers than in non-drinkers.

Background: The prognostic significance of resting heart rate and its therapeutic target in atrial fibrillation (AF) is uncertain. We sought to investigate the relationship between resting heart rate and cardiovascular outcomes in patients with non-paroxysmal AF (non-PAF). Methods: In this propensity score-weighted, multi-center prospective cohort study, 3217 patients with non-PAF were analyzed. Patients were categorized according to the baseline resting heart rate and cardiovascular outcomes were accessed for a median follow-up of 30 months. The primary outcome was a composite of cardiovascular death, heart failure hospitalization, and myocardial infarction/critical limb ischemia. Results: Freedom from primary outcome was longest among patients with resting heart rate 80–99 beats per minute (bpm) whereas shortest among those with ≤ 59 bpm (weighted log rank, p = 0.008). Compared with heart rate ≥ 100 bpm, resting heart rate 80–99 and 60–79 bpm was associated with reduced risk of primary outcome (weighted hazard ratio [WHR] 0.52, 95% confidence interval [CI] 0.32–0.84, p = 0.008 and WHR 0.58, 95% CI 0.37–0.92, p = 0.021 for heart rate 80–99 and 60–79 bpm, respectively). Using weighted restricted cubic spline curves, there was a U-shaped association between the resting heart rate and primary outcome with reduced risk of primary outcome in heart rate range of 68–99 bpm. This association was maintained regardless of atrioventricular node (AVN) blocker use or persistent/permanent AF (p for interaction 0.767 for AVN blocker use and 0.720 for AF type). Conclusion Resting heart rate was associated with cardiovascular outcomes in patients with non-PAF and those with resting heart rate between 68 and 99 bpm had lower risk of adverse cardiovascular events regardless of AVN blocker use or persistent/permanent AF.

Background and Objectives: In patients with atrial fibrillation (AF), females taking vitamin K antagonist are at higher risk of stroke or systemic embolism (SSE), bleeding and all-cause death than males. This study investigated the relationship between sex and adverse clinical events in a contemporary AF patient cohort taking anticoagulation. Methods: This prospective multicenter AF registry study comprised 6,067 patients with AF (mean age, 70±9 years; men, 59%) with intermediate to high risk of stroke (CHA 2 DS 2-VAscore ≥1) and receiving oral anticoagulation therapy. Adverse clinical outcomes, including SSE, bleeding, death were evaluated in patients stratified by sex and anticoagulation patterns. Results: Women were older and used more direct oral anticoagulants (85% vs. 78%, p<0.001) than men. During a median (25 the and 75 the percentiles) follow-up of 30 (24, 38) months, the incidence rate and risk of SSE (0.7 in women vs. 0.7 in men per 100 person-years) and major bleeding (0.1 in women vs. 0.1 in men per 100 person-years) were not different between the sexes. However, women had a lower all-cause death rate (0.4 in women vs. 0.6 in men per 100 person-years, hazard ratio: 0.48, 95% confidence interval: 0.25–0.91, p=0.025) than men. Conclusions In contemporary anticoagulation for AF, SSE and major bleeding risks did not differ between sexes. However, women showed a lower risk of all-cause death rate than men, indicating that the use of oral anticoagulants for treating AF in females does not appear to be a risk factor for adverse clinical events.

Purpose: The incidence of stroke and/or systemic thromboembolism (SSE) has not been properly evaluated in well-anticoagulated atrial fibrillation (AF) patients. This study investigated the incidence of SSE according to CHA2DS2-VASc score in contemporary well-anticoagulated Korean AF patients. Materials and Methods: From the prospective multicenter COmparison study of Drugs for symptom control and complication prEvention of Atrial Fibrillation (CODE-AF) registry, we identified 9503 patients with non-valvular AF (mean age, 68±8 years; female 35.5%) enrolled between June 2016 and May 2020 with eligible follow-up visits. Stroke incidence in the CODE-AF registry was compared with that in an oral anticoagulant (OAC)-naïve AF cohort from the Korean National Health Insurance database. Results: The usage rates of OACs and antiplatelet agents were 73.5% (non-vitamin K OACs, 56.4%; warfarin, 17.1%) and 23.8%, respectively. During a mean follow-up period of 26.3±9.6 months, 163 (0.78 per 100 person-years) patients had SSE. The incidence rate (per 100 person-years) of SSE was 0.77 in the total population, 0.26 in low-risk patients [CHA2DS2-VASc score 0 (male) or 1 (female)], and 0.88 in high-risk patients (CHA2DS2-VASc score ≥2). Contemporary AF patients had a stroke rate that was about one-fifth the stroke rate reported in a Korean OAC-naïve AF cohort. In this cohort, most risk factors for CHA2DS2-VASc score showed significant associations with SSE. Female sex was not associated with an increased risk of stroke/SSE in well-anticoagulated AF patients. Conclusion Contemporary AF patients have a stroke rate about one-fifth that in OAC-naïve AF patients and exhibit different stroke risk factors.

Background and Objectives: Atrial high-rate episodes (AHREs) can be continuously detected by cardiovascular implantable electronic devices (CIEDs); however, the predictors of clinically relevant AHREs are unclear. Methods: This prospective multicenter study monitored 816 patients (median age 73 years, 40.4% male) without atrial fibrillation (AF) from September 2017 to July 2020. AHREs was defined as a programmed atrial detection rate >220 beats/min. The reference values of 6 minutes and 6 hours were set to analyze clinical implication of AHREs based on previously published data that the 6 minutes excluded most episodes of oversensing. Results: During a median follow-up of 18 months (interquartile interval 9–26 months), AHREs with the longest durations of >15 seconds, >6 minutes, and >6 hours and clinically documented AF by electrocardiography were noted in 246 (30.1%), 112 (13.7%), 49 (6.0%), and 24 (2.9%) patients, respectively. Among patients developing AHREs >6 minutes, 102 (91.1%) of 112 patients were identified at the 6-month visit. Patients with AHREs >6 minutes had higher proportions of sick sinus syndrome, subjects with atrial premature beat >1% on Holter monitoring, and larger left atrium (LA) size than patients with AHREs ≤6 minutes.Multivariable logistic regression analysis showed that LA diameter >41 mm (odds ratio [OR], 2.08; 95% confidence interval [95% CI], 1.25–3.45), and sick sinus syndrome (OR, 3.22; 95% CI, 1.91–5.43) were associated with AHREs >6 minutes. Conclusions In patients with LA diameter >41 mm, and sick sinus syndrome before CIEDs implantation is associated with risk of developing AHREs >6 minutes.

Background and Objectives: Atrial high-rate episodes (AHREs) can be continuously detected by cardiovascular implantable electronic devices (CIEDs); however, the predictors of clinically relevant AHREs are unclear. Methods: This prospective multicenter study monitored 816 patients (median age 73 years, 40.4% male) without atrial fibrillation (AF) from September 2017 to July 2020. AHREs was defined as a programmed atrial detection rate >220 beats/min. The reference values of 6 minutes and 6 hours were set to analyze clinical implication of AHREs based on previously published data that the 6 minutes excluded most episodes of oversensing. Results: During a median follow-up of 18 months (interquartile interval 9–26 months), AHREs with the longest durations of >15 seconds, >6 minutes, and >6 hours and clinically documented AF by electrocardiography were noted in 246 (30.1%), 112 (13.7%), 49 (6.0%), and 24 (2.9%) patients, respectively. Among patients developing AHREs >6 minutes, 102 (91.1%) of 112 patients were identified at the 6-month visit. Patients with AHREs >6 minutes had higher proportions of sick sinus syndrome, subjects with atrial premature beat >1% on Holter monitoring, and larger left atrium (LA) size than patients with AHREs ≤6 minutes.Multivariable logistic regression analysis showed that LA diameter >41 mm (odds ratio [OR], 2.08; 95% confidence interval [95% CI], 1.25–3.45), and sick sinus syndrome (OR, 3.22; 95% CI, 1.91–5.43) were associated with AHREs >6 minutes. Conclusions In patients with LA diameter >41 mm, and sick sinus syndrome before CIEDs implantation is associated with risk of developing AHREs >6 minutes.

Background/Aims: Comparative occurrence of ischemic stroke for rhythm versus rate control strategy in patients with non-valvular atrial fibrillation (NVAF) is still inconclusive. The purpose of this study was to investigate whether the rhythm control strategy is associated with a lower risk of ischemic stroke compared to the rate control strategy in NVAF patients. Methods: The CODE-AF registry prospectively enrolled 6,280 consecutive patients who were treated for NVAF at 10 tertiary referral centers in South Korea. Of these, 2,513 NVAF patients (age, 67 ± 10 years; male, 61.8%) were clinically followed up for over 1-year and divided into rate and rhythm control groups. Results: Those treated with the rhythm control strategy were younger and had less proportions of underlying disease compared to those treated with the rate control strategy. After the propensity matching analysis, those treated with the rhythm control strategy had similar baseline characteristics including the CHA 2 DS 2 -VASC score compared to those treated with the rate control strategy.The rate of oral anticoagulation, all bleeding, and hospitalization were also similarly between the two groups. The incidence rate of ischemic stroke in the rhythm control group was significantly lower than in the rate control group (0.7 vs. 6.9 per 1,000 person-years, p = 0.011). Conclusions The rhythm control strategy demonstrated a beneficial effect to lower the risk of ischemic stroke during a 1-year follow-up compared to the rate control strategy.

Background/Aims: Atrial fibrillation (AF)-related stroke accounts for 20% of ischemic strokes. Rivaroxaban use in AF patients for preventing stroke and systemic embolism was approved in 2013 in Korea. This study was to investigate the safety and effectiveness of rivaroxaban use in Korean patients with non-valvular AF in a real-world setting. Methods: This was an analysis of the Korean patients in Xarelto for Prevention of Stroke in Patients with Atrial Fibrillation in Asia-Pacific (XANAP), which was a prospective, observational cohort study including patients with non-valvular AF starting rivaroxaban treatment to prevent stroke or non-central nervous system systemic embolism (non-CNS SE), conducted in 10 Asian countries. Results: A total of 844 patients were enrolled in the Korean portion of the XANAP study. In XANAP Korea, the mean age was 70.1 years and 62.6% were males. The mean CHADS2 score was 2.5 and the mean CHA2DS2-VASc score was 3.8. 47% of the patients had experienced prior stroke or non-CNS SE or transient ischemic attack. 73.6% of the patients had CHADS2 score ≥ 2. Incidence proportions of 0.8% of the patients (1.1 per 100 patient-years) developed adjudicated treatment-emergent major bleeding. Death was observed in 1.2% of the patients. The incidence of non-major bleeding as well as thromboembolic event were 8.4% (11.6 per 100 patient-years) and 1.5% (2.0 per 100 patient-years), respectively. Conclusions This study reaffirmed the consistent safety profile of rivaroxaban. We found consistent results with overall XANAP population for rivaroxaban in terms of safety in non-valvular AF patients for the prevention of stroke and non-CNS SE.

Background/Aims: Atrial fibrillation (AF)-related stroke accounts for 20% of ischemic strokes. Rivaroxaban use in AF patients for preventing stroke and systemic embolism was approved in 2013 in Korea. This study was to investigate the safety and effectiveness of rivaroxaban use in Korean patients with non-valvular AF in a real-world setting. Methods: This was an analysis of the Korean patients in Xarelto for Prevention of Stroke in Patients with Atrial Fibrillation in Asia-Pacific (XANAP), which was a prospective, observational cohort study including patients with non-valvular AF starting rivaroxaban treatment to prevent stroke or non-central nervous system systemic embolism (non-CNS SE), conducted in 10 Asian countries. Results: A total of 844 patients were enrolled in the Korean portion of the XANAP study. In XANAP Korea, the mean age was 70.1 years and 62.6% were males. The mean CHADS2 score was 2.5 and the mean CHA2DS2-VASc score was 3.8. 47% of the patients had experienced prior stroke or non-CNS SE or transient ischemic attack. 73.6% of the patients had CHADS2 score ≥ 2. Incidence proportions of 0.8% of the patients (1.1 per 100 patient-years) developed adjudicated treatment-emergent major bleeding. Death was observed in 1.2% of the patients. The incidence of non-major bleeding as well as thromboembolic event were 8.4% (11.6 per 100 patient-years) and 1.5% (2.0 per 100 patient-years), respectively. Conclusions This study reaffirmed the consistent safety profile of rivaroxaban. We found consistent results with overall XANAP population for rivaroxaban in terms of safety in non-valvular AF patients for the prevention of stroke and non-CNS SE.