Modifiable lifestyle factors and lifetime risk of atrial fibrillation: longitudinal data from the Korea NHIS-HealS and UK Biobank cohorts.

BACKGROUND: The reason for higher incidence of atrial fibrillation (AF) in Europe compared with East Asia is unclear. We aimed to investigate the association between modifiable lifestyle factors and lifetime risk of AF in Europe and East Asia, along with race/ethnic similarities and disparities. METHODS: 1:1 propensity score matched pairs of 242,763 East Asians and 242,763 White Europeans without AF were analyzed. Modifiable lifestyle factors considered were blood pressure, body mass index, cigarette smoking, diabetes, alcohol consumption, and physical activity, categorized as non-adverse or adverse levels. Lifetime risk of AF was estimated from the index age of 45 years to the attained age of 85 years, accounting for the competing risk of death. RESULTS: The overall lifetime risk of AF was higher in White Europeans than East Asians (20.9% vs 15.4%, p < 0.001). The lifetime risk of AF was similar between the two races in individuals with non-adverse lifestyle factor profiles (13.4% vs 12.9%, p = 0.575), whereas it was higher in White Europeans with adverse lifestyle factor profiles (22.1% vs 15.8%, p < 0.001). The difference in the lifetime risk of AF between the two races increased as the burden of adverse lifestyle factors worsened (1 adverse lifestyle factor; 4.3% to ≥ 3 adverse lifestyle factors; 11.2%). Compared with East Asians, the relative risk of AF in White Europeans was 23% and 62% higher for one (hazard ratio [HR] 1.23, 95% confidence interval [CI] 1.16-1.29) and ≥ 3 adverse lifestyle factors (HR 1.62, 95% CI 1.51-1.75), respectively. CONCLUSIONS: The overall higher lifetime risk of AF in White Europeans compared with East Asians might be attributable to adverse lifestyle factors. Adherence to healthy lifestyle factors was associated with the lifetime risk of AF of about 1 in 8 regardless of race/ethnicity.

Clinical Implications of Polypharmacy for Patients with New-Onset Atrial Fibrillation Based on Real-World Data: Observations from the Korea National Health Insurance Service Data.

Background: Polypharmacy is commonly observed in atrial fibrillation (AF) and is associated with poorer clinical outcomes. Our study aimed to elucidate the polypharmacy prevalence, its associated risk factors, and its relationship with adverse clinical outcomes using a 'real-world' database. Methods: This study included 451,368 subjects without prior history of AF (median age, 54 [interquartile range, 48.0-63.0] years; 207,748 [46.0%] female) from the Korea National Health Insurance Service-Health Screening (NHIS-HealS) database between 2002 and 2013. All concomitant medications prescribed were collected, and the intake of five or more concomitant drugs was defined as polypharmacy. During the follow-up, all-cause death, major bleeding events, transient ischemic attack (TIA) or ischemic stroke, and admission due to worsened heart failure were recorded. Results: Based on up to 7.7 (6.8-8.3) years of follow-up and 768,306 person-years, there were 12,241 cases of new-onset AF identified. Among patients with new-onset AF (40.0% females, median age 63.0 [54.0-70.0] years), the polypharmacy prevalence was 30.9% (3784). For newly diagnosed AF, factors, such as advanced age (with each increase of 10 years, odds ratios (OR) 1.32, 95% confidence interval (CI) 1.26-1.40), hypertension (OR 4.00, 95% CI 3.62-4.43), diabetes mellitus (OR 3.25, 95% CI 2.86-3.70), chronic obstructive pulmonary disease (COPD) (OR 3.00, 95% CI 2.51-3.57), TIA/ischemic stroke (OR 2.36, 95% CI 2.03-2.73), dementia history (OR 2.30, 95% CI 1.06-4.98), end-stage renal disease (ESRD) or chronic kidney disease (CKD) (OR 1.97, 95% CI 1.38-2.82), and heart failure (OR 1.95, 95% CI 1.69-2.26), were found to be independently correlated with the incidence of polypharmacy. Polypharmacy significantly increased the incidence and risk of major bleeding (adjusted hazard ratio (aHR) 1.26, 95% CI 1.12-1.41). The study observed a statistically significant increase in the incidence of all-cause mortality, however, the risk for all-cause mortality elevated but did not show significance (aHR 1.11, 95% CI 0.99-1.24). The risk of stroke and admission for heart failure did not change with polypharmacy. Conclusions: In our investigation using data from a nationwide database, polypharmacy was widespread in new-onset AF population and was related to major bleeding events. However, polypharmacy does not serve as an independent risk factor for adverse outcomes, with exception of major bleeding event. For AF patients, ensuring tailored medication for comorbidities as well as reducing polypharmacy are essential considerations.

All-Cause Death and Major Adverse Events in Atrial Fibrillation with Frailty: Observations from the Korea National Health Insurance Service Data.

Background: Atrial fibrillation (AF) is an indicator of frailty in old patients. This study aimed to investigate the effect of frailty on the use of oral anticoagulants (OAC) and clinical outcomes in a nationwide cohort of patients with new-onset AF. Methods: This study included 451,368 participants without AF from the Korea National Health Insurance Service-Health Screening cohort between 2002 and 2009. The Hospital Frailty Risk Score was retrospectively calculated for each patient using all available International Classification of Disease 10th revision diagnostic codes. According to the aggregate score, patients were divided into two groups: the participants without frailty ( < 5 points) and the participants with frailty ( ≥ 5 points). The primary outcome was death from any cause, and the secondary outcomes were cardiovascular death, ischemic stroke, major bleeding, and heart failure admission. Results: With up to 7.2 ± 1.5 years of follow-up, 11,953 participants (median age, 67 [interquartile range, 59.5-74.5] years; 7200 [60.2%] males) developed new-onset AF. Among the patients with AF, 3224 (26.9%) had frailty. Frailty was significantly associated with old age, female sex, polypharmacy, and other comorbidities. In patients with AF, frailty was negatively associated with OAC prescription after new-onset AF (p < 0.001). Compared to patients without frailty, patients with frailty had a significantly higher incidence and risk of all-cause death (hazard ratio [HR] 2.88, 95% confidence interval [CI] 2.65-3.14), cardiovascular death (HR 2.42, 95% CI 2.10-2.80), ischemic stroke (HR 2.25, 95% CI 2.02-2.51), major bleeding (HR 2.44, 95% CI 2.17-2.73), and heart failure admission (HR 1.29, 95% CI 1.09-1.52). In subgroup analysis, when compared to the non-OAC group, the risks associated with frailty were significantly lower in the OAC group for all-cause death, cardiovascular death, ischemic stroke, and heart failure admission. Conclusions: Frailty was negatively associated with the use of OAC and was a predictor of poor prognosis owing to the association of frailty with death, thromboembolic events, bleeding, and heart failure admission. However, OAC use was associated with lower risks related to frailty for all-cause death and major adverse cardiovascular events in patients with AF.

Early Rhythm Control Therapy for Atrial Fibrillation in Low-Risk Patients : A Nationwide Propensity Score-Weighted Study.

BACKGROUND: Rhythm control is associated with lower risk for adverse cardiovascular outcomes compared with usual care among patients recently diagnosed with atrial fibrillation (AF) with a CHA2DS2-VASc score of approximately 2 or greater in EAST-AFNET 4 (Early Treatment of Atrial Fibrillation for Stroke Prevention Trial). OBJECTIVE: To investigate whether the results can be generalized to patients with low stroke risk. DESIGN: Population-based cohort study. SETTING: Nationwide claims database of the Korean National Health Insurance Service. PARTICIPANTS: 54 216 patients with AF having early rhythm control (antiarrhythmic drugs or ablation) or rate control therapy that was initiated within 1 year of the AF diagnosis. MEASUREMENTS: The effect of early rhythm control on the primary composite outcome of cardiovascular death, ischemic stroke, hospitalization for heart failure, or myocardial infarction was compared between eligible and ineligible patients for EAST-AFNET 4 (CHA2DS2-VASc score, approximately 0 to 1) using propensity overlap weighting. RESULTS: In total, 37 557 study participants (69.3%) were eligible for the trial (median age, 70 years; median CHA2DS2-VASc score, 4), among whom early rhythm control was associated with lower risk for the primary composite outcome than rate control (hazard ratio, 0.86 [95% CI, 0.81 to 0.92]). Among the 16 659 low-risk patients (30.7%) who did not meet the inclusion criteria (median age, 54 years; median CHA2DS2-VASc score, 1), early rhythm control was consistently associated with lower risk for the primary outcome (hazard ratio, 0.81 [CI, 0.66 to 0.98]). No significant differences in safety outcomes were found between the rhythm and rate control strategies regardless of trial eligibility. LIMITATION: Residual confounding. CONCLUSION: In routine clinical practice, the beneficial association between early rhythm control and cardiovascular complications was consistent among low-risk patients regardless of trial eligibility. PRIMARY FUNDING SOURCE: The Ministry of Health and Welfare and the Ministry of Food and Drug Safety, Republic of Korea.

Effectiveness and Safety of Anticoagulation Therapy in Frail Patients With Atrial Fibrillation.

BACKGROUND: Frail patients with atrial fibrillation (AF) are less likely to receive anticoagulation than nonfrail patients with AF despite frailty being associated with poorer clinical outcomes including stroke. Using a population-based cohort, we sought to assess the effectiveness and safety of oral anticoagulants (OACs) in frail patients with AF. METHODS: This retrospective cohort study analyzed 83 635 patients aged at least 65 years with AF and frailty (≥5 Hospital Frailty Risk Score) between January 1, 2013 and December 31, 2016 from the Korean National Health Insurance Service database. To account for the differences between patients receiving OAC or not and across different OAC regimens, propensity score-weighting was used. Net adverse clinical event, defined as the first event of ischemic stroke, major bleeding, or cardiovascular death, was compared. In addition, each individual outcome was examined separately. RESULTS: In the study population (57.1% women; mean age, 78.5±7.2 years), a total of 14 968 net adverse clinical event, 3718 ischemic stroke, 5536 major bleeding, and 6188 cardiovascular death occurred. In comparison with no OAC use, OAC use was associated with lower risks of net adverse clinical event (hazard ratio, 0.78 [95% CI, 0.75-0.82]), ischemic stroke (hazard ratio, 0.91 [95% CI, 0.86-0.97]), and cardiovascular death (hazard ratio, 0.52 [95% CI, 0.49-0.55]), but no difference was observed for major bleeding (hazard ratio, 1.02 [95% CI, 0.95-1.10]). Compared with warfarin, all four individual direct OAC were associated with decreased risks of net adverse clinical event, ischemic stroke, major bleeding, and cardiovascular death. The associations for OAC use (compared to no OAC use) or direct OAC use (compared to warfarin) with favorable outcomes were more prominent in individuals with a higher CHA2DS2-VASc score of at least 3. CONCLUSIONS: Among frail patients with AF, OAC treatment was associated with a positive net clinical outcome. Direct OACs provided lower incidences of stroke, bleeding, and mortality, compared with warfarin.

Association between Physical Activity and the Risk of Mortality and Hospitalization in Older Korean Adults with Heart Failure.

Background: Regular exercise improves the functional ability and quality of life of patients with heart failure (HF). However, studies on the results of intensity of exercise in the older population are scarce, especially in the Asian population. Method and Results: A total of 8982 older people (age ≥ 65 years) with HF were selected from the Korean National Health Insurance Service-Senior database (2005-2012). Participants were stratified according to the levels of physical activity per week as follows: (1) inactive group; (2) insufficiently active group: 1-499 metabolic equivalent task minutes (MET-min)/week; (3) active group: 500-999 MET-min/week; and (4) highly active group: ≥ 1000 MET-min/week. During a median follow-up period of 3.2 years, the incidence and risk of mortality were reduced in the insufficiently active (6.7 vs. 4.2 per 100 person-years, adjusted hazard ratio [HR], 0.82; 95% confidence interval [CI], 0.71-0.94; p < 0.001), active (3.8 per 100 person-years; HR, 0.81; 95% CI, 0.70-0.95; p = 0.010), and highly active (2.4 per 100 person-years; HR, 0.52; 95% CI, 0.41-0.67; p < 0.001) groups compared to inactive patients. Conclusions: In older Asians with HF, increased physical activity reduced the risk of all-cause mortality. The mortality-reducing benefit started at a lower physical activity compared to the World Health Organization guideline (500-999 MET-min/week), and the risk decreased with more physical activity.

Association of rhythm control with incident dementia among patients with atrial fibrillation: a nationwide population-based cohort study.

BACKGROUND: Atrial fibrillation (AF) increases the risk of dementia, and catheter ablation of AF may be associated with a lower risk of dementia. We investigated the association of a rhythm-control strategy for AF with the risk of dementia, compared with a rate-control strategy. METHODS: This population-based cohort study included 41,135 patients with AF on anticoagulation who were newly treated with rhythm-control (anti-arrhythmic drugs or ablation) or rate-control strategies between 1 January 2005 and 31 December 2015 from the Korean National Health Insurance Service database. The primary outcome was all-cause dementia, which was compared using propensity score overlap weighting. RESULTS: In the study population (46.7% female; median age: 68 years), a total of 4,039 patients were diagnosed with dementia during a median follow-up of 51.7 months. Rhythm control, compared with rate control, was associated with decreased dementia risk (weighted incidence rate: 21.2 versus 25.2 per 1,000 person-years; subdistribution hazard ratio [sHR] 0.86, 95% confidence interval [CI] 0.80-0.93). The associations between rhythm control and decreased dementia risk were consistently observed even after censoring for incident stroke (sHR 0.89, 95% CI 0.82-0.97) and were more pronounced in relatively younger patients and those with lower CHA2DS2-VASc scores. Among dementia subtypes, rhythm control was associated with a lower risk of Alzheimer's disease (sHR 0.86, 95% CI 0.79-0.95). CONCLUSIONS: Among anticoagulated patients with AF, rhythm control was associated with a lower risk of dementia, compared with rate control. Initiating rhythm control in AF patients with fewer stroke risk factors might help prevent subsequent dementia.

Increased risk of ischemic stroke and systemic embolism in hyperthyroidism-related atrial fibrillation: A nationwide cohort study.

BACKGROUND: We aimed to evaluate the long-term risk of ischemic stroke/systemic embolism of hyperthyroidism-related AF. METHODS: This retrospective population-based cohort study included records of 1,034,099 atrial fibrillation patients between 2005 and 2016 from the Korean National Health Insurance Service database. After exclusion, we identified 615,724 oral anticoagulation-naïve patients aged ≥18 years with new-onset non-valvular atrial fibrillation, of whom 20,773 had hyperthyroidism-related atrial fibrillation. After 3:1 propensity score matching, ischemic stroke and systemic embolism occurrences were compared between hyperthyroidism-related and non-hyperthyroidism-related ("nonthyroidal") atrial fibrillation patients. RESULTS: After exclusion, we identified 615,724 oral anticoagulation-naïve AF patients of whom 20,773 had hyperthyroidism-related AF. Median follow-up duration was 5.9 years. Hyperthyroidism-related AF patients had significantly higher risks of ischemic stroke and systemic embolism than nonthyroidal AF patients (1.83 vs 1.62 per 100-person year, hazard ratio[HR], 1.13; 95% confidence interval[CI], 1.07 to 1.19; P < 0.001). This risk was 36% higher in hyperthyroidism-related than in nonthyroidal AF patients within 1 year of atrial fibrillation diagnosis (3.65 vs 2.67 per 100-person year, HR, 1.36; 95% CI, 1.24 - 1.50; P < 0.001). This difference was also observed in the CHA2DS2-VASc score subgroup analysis. The risk of ischemic stroke and systemic embolism significantly decreased in patients treated for hyperthyroidism (HR, 0.64; 95% CI, 0.58 to 0.70; P < 0.001). CONCLUSIONS: Hyperthyroidism-related AF patients have high risks of ischemic stroke and systemic embolism like nonthyroidal AF, especially when initially diagnosed. This risk is reduced by treating hyperthyroidism.

Risk of sick sinus syndrome in patients diagnosed with atrial fibrillation: A population-based cohort.

BACKGROUND: Sinoatrial node dysfunction and atrial fibrillation (AF) frequently coexist and interact with each other, often to initiate and perpetuate each other. OBJECTIVE: To determine the effect of AF on the incidence and risk of sick sinus syndrome (SSS). METHODS: The association of incident AF with the development of incident SSS was assessed from 2004 to 2014 in 302 229 SSS- and pacemaker-free subjects aged ≥60 years in the Korea National Health Insurance Service-Senior cohort. RESULTS: During an observation period of 1 854 800 person-years, incident AF was observed in a total of 12 797 subjects (0.69%/year). The incidence of SSS was 3.4 and 0.2 per 1000 person-years in the propensity score-matched incident AF and no-AF groups, respectively. After adjustment, the significantly increased risk of SSS was observed in the incident AF group, with a hazard ratio (HR) of 13.4 (95% confidence interval [CI]: 8.4-21.4). This finding was consistently observed after censoring for heart failure (HR: 16.0; 95% CI: 9.2-28.0) or heart failure/myocardial infarction (HR: 16.6; 95% CI: 9.3-29.7). Incident AF also was associated with an increased risk of pacemaker implantation related with both SSS (HR: 21.8; 95% CI: 8.7-18.4) and atrioventricular (AV) block (HR: 9.5; 95% CI: 4.9-18.4). These results were consistent regardless of sex and comorbidities. CONCLUSION: Incident AF was associated with more than 10 times increased risk of SSS in an elderly population regardless of comorbidities. The risk of pacemaker implantations related with both sinus node dysfunction and AV block was increased in the elderly population with incident AF.

Association of anticoagulant therapy with risk of dementia among patients with atrial fibrillation.

AIMS: To investigate the risk of dementia in atrial fibrillation (AF) patients treated with different oral anticoagulants (OACs). METHODS AND RESULTS: This observational, population-based cohort study enrolled 53 236 dementia-free individuals with non-valvular AF who were aged ≥50 years and newly prescribed OACs from 1 January 2013 to 31 December 2016 from the Korean National Health Insurance Service database. Propensity score matching was used to compare the rates of dementia between users of non-vitamin K antagonist oral anticoagulant (NOAC) (dabigatran, rivaroxaban, and apixaban) and warfarin and to compare each individual NOAC with warfarin. Propensity score weighting analyses were also performed. In the study population (41.3% women; mean age: 70.7 years), 2194 had a diagnosis of incident dementia during a mean follow-up of 20.2 months. Relative to propensity-matched warfarin users, NOAC users tended to be at lower risk of dementia [hazard ratio (HR) 0.78, 95% confidence interval (CI) 0.69-0.90]. When comparing individual NOACs with warfarin, all the three NOACs were associated with lower dementia risk. In pairwise comparisons among NOACs, rivaroxaban was associated with decreased dementia risk, compared with dabigatran (HR 0.83, 95% CI 0.74-0.92). Supplemental propensity-weighted analyses showed consistent protective associations of NOACs with dementia relative to warfarin. The associations were consistent irrespectively of age, sex, stroke, and vascular disease and more prominent in standard dose users of NOAC. CONCLUSION: In this propensity-matched and -weighted analysis using a real-world population-based cohort, use of NOACs was associated with lower dementia risk than use of warfarin among non-valvular AF patients initiating OAC treatment.

Frailty and the Effect of Catheter Ablation in the Elderly Population With Atrial Fibrillation　- A Real-World Analysis.

BACKGROUND: It is unclear whether catheter ablation is beneficial for frail elderly patients with atrial fibrillation (AF). This study evaluated the effect of ablation on outcomes in frail elderly patients with AF.Methods and Results:From the Korean National Health Insurance Service database, 194,928 newly diagnosed AF patients were treated with ablation or medical therapy (rhythm or rate control) between 2005 and 2015. Among these patients, the study included 1,818 (ablation; n=119) frail and 1,907 (ablation; n=230) non-frail elderly (≥75 years) patients. Propensity score matching was used to correct for differences between groups. During 28 months (median) follow up, the risk of all-cause death, composite outcome (all-cause death, heart failure admission, stroke/systemic embolism, and sudden cardiac arrest), and each outcome did not change after ablation in frail elderly patients. However, in non-frail elderly patients, ablation was associated with a lower risk of all-cause death (3.5 and 6.2 per 100 person-years; hazard ratio [HR] 0.48; 95% confidence interval [CI] 0.30-0.79; P=0.004), and composite outcome (6.9 and 11.2 per 100 person-years; HR 0.54; 95% CI 0.38-0.75; P<0.001). CONCLUSIONS: Ablation may be associated with a lower risk of death and composite outcome in non-frail elderly, but the beneficial effect of ablation was not significant in frail elderly patients with AF. The effect of frailty on the outcome of ablation should be evaluated in further studies.

Impact of abdominal obesity on outcomes of catheter ablation in Korean patients with atrial fibrillation.

BACKGROUND: Effects of abdominal obesity on outcomes of atrial fibrillation (AF) ablation remains ill-defined. Here, we evaluated the impact of abdominal obesity on the long-term efficacy and safety of catheter AF ablation among Korean patients. METHODS: We utilised the Korean National Health Insurance Service database to identify patients who underwent AF ablation. Abdominal obesity was defined as waist circumference ≥90 cm (males) and ≥85 cm (females). The primary endpoint was AF recurrence and secondary endpoints were ischaemic stroke, intracranial haemorrhage and death. Additionally, safety endpoints of peri-procedural complications were studied. RESULTS: Among 5397 patients (median age 58 [IQR 51-65] years; 23.6% females), abdominal obesity was present in 1759 (32.6%). The rate of AF recurrence was not statistically different between the groups at 1-year (10.3 vs 8.7 events/100-PYs, P = .078), though abdominal obesity was associated with significantly higher rates of AF recurrence at 3-year (7.6 vs 6.3 events/100-PYs, P = .008) and 6-year (6.3 vs 5.2 events/100-PYs, P = .004) follow-ups. Kaplan-Meier survival analysis found significantly higher rates of AF recurrence in patients with obesity based on body mass index (BMI) and waist circumference (log-rank for trend P = .006). Using multivariable regression analysis, obesity by both BMI and waist circumference was an independent predictor for AF recurrence (HR 1.21 [95% CI, 1.05-1.40]), after accounting for other risk factors. There was a trend for increased rates of ischaemic stroke at 3-year and 6-year follow-ups in patients with abdominal obesity. Furthermore, this group of patients had a greater rate of intracranial haemorrhage. All-cause death was comparable between both groups. Total peri-procedural complications were not associated with abdominal obesity. CONCLUSION: Abdominal obesity as indicated by waist circumference was associated with a greater burden of concomitant diseases and an independent risk factor for long-term redo AF intervention following catheter ablation but had no effects on total peri-procedural complications.

Less dementia after catheter ablation for atrial fibrillation: a nationwide cohort study.

AIMS: Accumulating evidence shows that atrial fibrillation (AF) is associated with an increased risk of dementia. Catheter ablation for AF prolongs the duration of sinus rhythm, thereby improving the quality of life. We investigated the association of catheter ablation for AF with the occurrence of dementia. METHODS AND RESULTS: Using the Korean National Health Insurance Service database, among 194 928 adults with AF treated with ablation or medical therapy (antiarrhythmic or rate control drugs) between 1 January 2005 and 31 December 2015, we studied 9119 patients undergoing ablation and 17 978 patients managed with medical therapy. The time-at-risk was counted from the first medical therapy, and ablation was analysed as a time-varying exposure. Propensity score-matching was used to correct for differences between the groups. During a median follow-up of 52 months, compared with patients with medical therapy, ablated patients showed lower incidence and risk of overall dementia (8.1 and 5.6 per 1000 person-years, respectively; hazard ratio 0.73, 95% confidence interval 0.58-0.93). The associations between ablation and dementia risk were consistently observed after additionally censoring for incident stroke (hazard ratio 0.76, 95% confidence interval 0.61-0.95) and more pronounced in cases of ablation success whereas no significant differences observed in cases of ablation failure. Ablation was associated with lower risks of dementia subtypes including Alzheimer's disease and vascular dementia. CONCLUSION: In this nationwide cohort of AF patients treated with catheter ablation or medical therapy, ablation was associated with decreased dementia risk. This relationship was evident after censoring for stroke and adjusting for clinical confounders.

The optimal drug adherence to maximize the efficacy and safety of non-vitamin K antagonist oral anticoagulant in real-world atrial fibrillation patients.

AIMS: To investigate the association between adherence to non-vitamin K antagonist oral anticoagulant (NOAC) and clinical outcomes and to determine the optimal cut-off level of NOAC adherence among patients with atrial fibrillation (AF). METHODS AND RESULTS: Using the Korean National Health Insurance Service database, we identified 96 197 patients with non-valvular AF who initiated NOAC or warfarin in 2013-16. We compared clinical outcomes between adherent [proportion of days covered (PDC) ≥80%] vs. non-adherent (PDC <80%) NOAC users, and further with warfarin users. We assessed the outcomes according to different levels of adherence. The proportion of adherent NOAC users was 64.0%. Compared with non-adherent NOAC users, adherent NOAC users were at lower risks of ischaemic stroke/systemic embolism (SE) [adjusted hazard ratio (aHR) 0.73, 95% confidence interval (CI) 0.69-0.79], and myocardial infarction (aHR 0.82, 95% CI 0.72-0.93), whereas there was no significant risk alteration for major bleeding (aHR 1.01, 95% CI 0.91-1.11). Compared with warfarin, non-adherent NOAC use failed to have better efficacy against ischaemic stroke/SE (aHR 0.99, 95% CI 0.93-1.05) and rather had increased risk of myocardial infarction (aHR 1.13, 95% CI 1.03-1.25). In NOAC users, the risks of adverse outcomes decreased according to gradual increase of adherence rates with the lowest risks in ≥90%, except for major bleeding in which there were no significant associations. CONCLUSIONS: In an adherence level-dependent fashion, adherent use of NOAC showed better clinical outcomes without increasing bleeding risk. Maintaining ≥90% of adherence optimizes effectiveness of NOAC therapy without compromising its safety.

Risk of dementia in stroke-free patients diagnosed with atrial fibrillation: data from a population-based cohort.

AIMS: Atrial fibrillation (AF) is generally regarded as a risk factor for dementia, though longitudinal studies assessing the association between AF and dementia have shown inconsistent results. This study aimed to determine the effect of AF on the risk of developing dementia using a longitudinal, community-based, and stroke-free elderly cohort. METHODS AND RESULTS: The association of incident AF with the development of incident dementia was assessed from 2005 to 2012 in 262 611 dementia- and stroke-free participants aged ≥60 years in the Korea National Health Insurance Service-Senior cohort. Incident AF was observed in 10 435 participants over an observational period of 1 629 903 person-years (0.64%/year). During the observational period, the incidence of dementia was 4.1 and 2.7 per 100 person-years in the incident AF and propensity score-matched AF-free groups, respectively. After adjustment, the risk of dementia was significantly increased by incident AF with a hazard ratio (HR) of 1.52 [95% confidence interval (CI) 1.43-1.63], even after censoring for stroke (1.27, 95% CI 1.18-1.37). Incident AF increased the risk of both Alzheimer (HR 1.31, 95% CI 1.20-1.43) and vascular dementia (HR 2.11, 95% CI 1.85-2.41). Among patients with incident AF, oral anticoagulant use was associated with a preventive effect on dementia development (HR 0.61, 95% CI 0.54-0.68), and an increasing CHA2DS2-VASc score was associated with a higher risk of dementia. CONCLUSION: Incident AF was associated with an increased risk of dementia, independent of clinical stroke in an elderly population. Oral anticoagulant use was linked with a decreased incidence of dementia.

Effect of hypertension duration and blood pressure level on ischaemic stroke risk in atrial fibrillation: nationwide data covering the entire Korean population.

AIMS: There are a paucity of data on the association of duration of hypertension and blood pressure (BP) level with risk of ischaemic stroke in patients with atrial fibrillation (AF). Our objective was to investigate the association between duration of hypertension and secondly, BP levels with risk of ischaemic stroke among patients with AF. METHODS AND RESULTS: A total of 246 459 oral anticoagulant-naïve non-valvular AF patients were enrolled from Korea National Health Insurance Service (NHIS) database (2005-2015). The risk of ischaemic stroke according to the duration of hypertension and systolic BP (SBP) levels were assessed. One-year increase of hypertension duration continuously increased the adjusted risk of ischaemic stroke (95% confidence interval 1.07-1.09) until 7 years, and reached a plateau with adjusted hazard ratio of 1.6. Risk of ischaemic stroke increased linearly with the increase of hypertension duration in patients younger than 65 years of age, whereas the risk reached a plateau in patients aged 65 years or older. In all baseline and pre-AF average SBP subgroups, longer duration of hypertension before AF was associated with higher ischaemic stroke risk than shorter duration of hypertension (all P-values for trends <0.01). However, the effect of long-term hypertension was not observed in patients with strictly well-controlled pre-AF average SBP of less than 120 mmHg. CONCLUSION: The increase of hypertension duration was associated with the increased risk of ischaemic stroke. However, this long-term effect of hypertension duration can be attenuated by long-term strict SBP control throughout the entire duration of hypertension.

Prevalence and Associated Stroke Risk of Human Immunodeficiency Virus-Infected Patients With Atrial Fibrillation　- A Nationwide Cohort Study.

BACKGROUND: Patients infected with human immunodeficiency virus (HIV) are at increased risk of cardiovascular diseases. However, little is known regarding the risk of ischemic stroke in HIV-infected individuals with atrial fibrillation (AF).Methods and Results:From the Korean National Health Insurance Service (NHIS) database from January 1, 2005 to December 31, 2016, we analyzed 962,116 patients with prevalent non-valvular AF aged ≥18 years. The overall HIV prevalence in AF patients was 0.17% (1,678 of 962,116). Oral anticoagulant (OAC)-naïve non-valvular AF (NVAF) patients with HIV had increased risks of ischemic stroke/systemic embolism (SE) [adjusted hazard ratio (HR) 1.37; 95% confidence interval (CI), 1.21-1.54], and major bleeding (adjusted HR 1.29; 95% CI, 1.15-1.46), compared with those without HIV. The incidence of ischemic stroke/SE in NVAF patients with HIV without any risk factors was similar to that of those without HIV at intermediate risk (i.e., male CHA2DS2-VASc score of 1) (2.04 vs. 2.18 events per 100 person-years). However, the use of OACs in AF patients with HIV was suboptimal, being only 8.9% at the time of AF diagnosis and 31.8% throughout the study period. CONCLUSIONS: The risks of ischemic stroke/SE and major bleeding were significantly higher in HIV-infected patients compared with non-HIV-infected patients with AF. Despite this, the actual use of OACs among AF patients with HIV was suboptimal.

Age Threshold for Ischemic Stroke Risk in Atrial Fibrillation.

Background and Purpose- Although older age is one of the most important risk factor for stroke in atrial fibrillation (AF), the appropriate age threshold (eg, CHA2DS2-VASc score [congestive heart failure, hypertension, age ≥75 years (doubled), diabetes mellitus, prior stroke or transient ischemic attack (doubled), vascular disease, age 65-74 years, female], 1 point for age 65-74 years, 2 points for age ≥75 years) for increased risk is controversial because actual age thresholds may differ between countries and ethnic groups. We investigated the age threshold for ischemic stroke risk among Asian AF patients. Methods- Using National Health Insurance Service database, including 426 650 oral anticoagulant-naive nonvalvular AF patients from 2005 to 2015, with ≤2 nongender-related CHA2DS2-VASc risk scores (CHA2DS2-VASc score 0-2 in males, 1-3 in females), we assessed the risk of ischemic stroke in AF patients according to the age. Results- Patients who fulfill the age risk criterion (age, 65-74 years) without other risk factors showed a significantly higher risk of stroke (4.76 per 100 person-years [100PY]; adjusted hazard ratio, 2.25; 95% confidence interval [CI], 2.17-2.36) compared with patients with 1 risk score other than age (1.87/100PY). Patients aged 55 to 59 years with no risk factors showed similar risk of stroke (1.94/100PY; adjusted hazard ratio, 0.95; 95% confidence interval, 0.90-1.00) than patients with 1 risk score (2.06/100PY). Patients aged 65 to 69 years and no other risk factors had similar stroke risk (4.08/100PY; adjusted hazard ratio, 0.93; 95% confidence interval, 0.90-0.97) than patients with 2 nongender-related risk scores (4.42/100PY). Conclusions- Older age is the most important predictor of ischemic stroke in AF, particularly for patients with low to intermediate risk of stroke. These nationwide data suggest lowering the current age threshold (age, ≥65 years) in the CHA2DS2-VASc score to age ≥55 years might be appropriate among Asian patients with AF.

Impact of Renal Function on Outcomes With Edoxaban in Real-World Patients With Atrial Fibrillation.

Background and Purpose- Edoxaban is a direct oral factor Xa inhibitor with proven efficacy and safety among patients with atrial fibrillation. Concerns have been raised about an excess of stroke among patients with creatinine clearance (CrCl) >95 mg/mL treated with edoxaban. We assessed the real-world effectiveness and safety of edoxaban in atrial fibrillation patients in relation to CrCl. Methods- In the Korean National Health Insurance Service data during the period from January to December 2016, we identified 9537 edoxaban-treated patients. Effectiveness and safety outcomes were compared between high-dose edoxaban regimen (HDER, 60 mg daily, n=2840) and a propensity score-matched warfarin group (n=2840) and between low-dose edoxaban regimen (LDER, 30 mg daily, n=3016) and matched warfarin group (n=3016). Results- The median follow-up period was 5.0 months (interquartile range, 2-7 months). The mean age was 68 years, and 63% were men in HDER group, and the mean age was 73 years, and 52% were men in LDER group. Compared with warfarin, both HDER and LDER significantly decreased the risk for ischemic stroke or systemic embolism (S/SE; HDER: adjusted hazard ratio [aHR], 0.44; 95% CI, 0.31-0.64; LDER: aHR, 0.57; 95% CI, 0.42-0.78), major bleeding (HDER: aHR, 0.40; 95% CI, 0.26-0.61; LDER: aHR, 0.61; 95% CI, 0.43-0.85), and mortality (HDER: aHR, 0.34; 95% CI, 0.22-0.53; LDER: aHR, 0.55; 95% CI, 0.41-0.73). In patients with CrCl >95 mL/min, the incidence of S/SE was higher with LDER than warfarin and comparable between HDER and warfarin group. There was lower effectiveness for the prevention of S/SE with LDER compared with warfarin at higher CrCl levels ( P for interaction=0.023). Conclusions- In real-world practice, both doses of edoxaban were associated with reduced risks for S/SE, major bleeding, and mortality compared with warfarin. LDER had lower effectiveness for the prevention of S/SE compared with warfarin at higher levels of CrCl (>95 mL/min).

10-year nationwide trends of the incidence, prevalence, and adverse outcomes of non-valvular atrial fibrillation nationwide health insurance data covering the entire Korean population.

BACKGROUND: Most data on the clinical epidemiology of atrial fibrillation (AF) are reported from Western populations, and data for Asians are limited. We aimed to investigate the 10-year trends of the prevalence and incidence of non-valvular AF and provide prevalence projections till 2060 in Korea. We also investigated the annual risks of adverse outcomes among patients with AF. METHODS: Using the Korean National Health Insurance Service database involving the entire Korean population, a total of 679,416 adults with newly diagnosed AF were identified from 2006 to 2015. The incidence and prevalence of AF and risk of adverse outcomes following AF onset were assessed. RESULTS: The prevalence of AF progressively increased by 2.10-fold from 0.73% in 2006 to 1.53% in 2015. The trend of its incidence was flat with a 10-year overall incidence of 1.77 per 1,000 person-years. The prevalence of AF is expected to reach 5.81% (2,290,591 patients with AF) in 2060. For a decade, the risk of all-cause mortality following AF declined by 30% (adjusted hazard ratio [HR]: 0.70, 95% confidence interval [CI]: 0.68-0.72), heart failure by 52% (adjusted HR: 0.48, 95% CI: 0.44-0.51), and ischemic stroke by 9% (adjusted HR: 0.91, 95% CI: 0.88-0.93). CONCLUSIONS: The burden of AF among Asian patients is increasing. Although the overall risks of cardiovascular events and death following AF onset have decreased over a decade, the event rates are still high. Optimized management of any associated comorbidities should be part of the holistic management approach for patients with AF.