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.

CHA2DS2-VASc and HAS-BLED scores were 2.6±1.7 and 1.8±1.1, respectively. In patients with high stroke risk (CHA2DS2-VASc ≥2), OACs were used in 83.2%, including direct OAC in 68.8%. The most important factors for non-OAC treatment were end-stage renal disease [odds ratio (OR) 0.27; 95% confidence interval (CI): 0.19–0.40], myocardial infarct (OR 0.53; 95% CI: 0.40–0.72), and major bleeding (OR 0.57; 95% CI: 0.39–0.84). Female sex (OR 1.40; 95% CI: 1.21–1.61), cancer (OR 1.78; 95% CI: 1.38–2.29), and smoking (OR 1.60; 95% CI: 1.15–2.24) were factors favoring direct OAC use over warfarin. Among patients receiving OACs, the rate of combined antiplatelet agents was 7.8%. However, 73.6% of patients did not have any indication for a combination of antiplatelet agents.CONCLUSION: Renal disease and history of valvular heart disease were associated with warfarin use, while cancer and smoking status were associated with direct OAC use in high stroke risk patients. The combination of antiplatelet agents with OAC was prescribed in 73.6% of patients without definite indications recommended by guidelines.]]>
Anticoagulants ; Atrial Fibrillation ; Female ; Heart Valve Diseases ; Hemorrhage ; Humans ; Kidney Failure, Chronic ; Male ; Multivariate Analysis ; Myocardial Infarction ; Platelet Aggregation Inhibitors ; Prospective Studies ; Smoke ; Smoking ; Stroke ; Warfarin

Background/Aims: Efforts to reduce stroke in patients with atrial fibrillation (AF) have focused on increasing physician adherence to oral anticoagulant (OAC) guidelines; however, the high early discontinuation rate of vitamin K antagonists (VKAs) is a limitation. Although non-VKA OACs (NOACs) are more convenient to administer than warfarin, their lack of monitoring may predispose patients to nonpersistence. We compared the persistence of NOAC and VKA treatment for AF in real-world practice. Methods: In a prospective observational registry (COmparison study of Drugs for symptom control and complication prEvention of Atrial Fibrillation [CODE-AF] registry), 7,013 patients with nonvalvular AF (mean age 67.2 ± 10.9 years, women 36.4%) were consecutively enrolled between June 2016 and June 2017 from 10 tertiary hospitals in Korea. This study included 3,381 patients who started OAC 30 days before enrollment (maintenance group) and 572 patients who newly started OAC (new-starter group). The persistence rate of OAC was evaluated. Results: In the maintenance group, persistence to OAC declined during 6 months, to 88.3% for VKA and 95.5% for NOAC (p < 0.0001). However, the persistence rate was not different among NOACs. In the new-starter group, persistence to OAC declined during 6 months, to 78.9% for VKA and 92.1% for NOAC (p < 0.0001). The persistence rate was lower for rivaroxaban (83.7%) than apixaban (94.6%) and edoxaban (94.1%, p < 0.001). In the new-starter group, diabetes, valve disease, and cancer were related to nonpersistence of OAC. Conclusions Nonpersistence was significantly lower with NOAC than VKA in both the maintenance and new-starter groups. In only the new-starter group, apixaban or edoxaban showed higher persistence rates than rivaroxaban.

Background: Symptom burden is an important factor in determining the treatment of atrial fibrillation (AF). AF is frequently accompanied by heart failure (HF). This study investigated the characteristics of AF symptoms with concomitant HF. Methods: A total of 4885 patients with AF were consecutively enrolled through a prospective observational registry (the Comparison Study of Drugs for Symptom Control and Complication Prevention of Atrial Fibrillation [CODE-AF] registry). Clinically diagnosed HF was divided into three categories (preserved, mid-range, and reduced ejection fraction [EF]). Symptom severity was assessed using the European Heart Rhythm Association (EHRA) classification. Results: The presence of AF-related symptoms was comparable irrespective of concomitant HF. Patients with HF with reduced EF demonstrated severe (EHRA classes 3 and 4) and atypical symptoms. HF with preserved EF was also associated with atypical symptoms. Female sex and AF type were associated with the presence of symptoms in AF without HF, and non-maintenance of sinus rhythm and increased left atrial pressure (E/e′ ≥ 15) were factors related to the presence of symptoms in AF with HF. Conclusion AF with concomitant HF presented with more severe and atypical symptoms than AF without HF. Maintaining the sinus rhythm and reducing the E/e’ ratio are important factors for reducing symptoms in AF with concomitant HF.

Purpose: Dose reduction of non-vitamin K antagonist oral anticoagulants (NOACs) is indicated in patients with atrial fibrillation (AF) with renal impairment. This study investigated anticoagulation patterns and outcomes in patients with chronic kidney disease (CKD). Materials and methods: In a prospective observational registry (CODE-AF), 3445 patients with non-valvular AF including 1129 with CKD (estimated glomerular filtration rate ≤ 60 mL min−1 1.73 m−2) were identified between June 1, 2016, and July 3, 2017. Results: Compared with patients with no-CKD, patients with CKD more frequently had a high stroke risk (94.9% vs. 67.0%, p < 0.001) and higher NOAC usage rate (61.1% vs. 47.8%, p < 0.001). Among 718 patients with renal indication for dose reduction (RIDR), 7.5% were potentially overdosed. Among 2587 patients with no-RIDR, 79% were potentially underdosed. Compared with patients with no-RIDR, the underdose rates of dabigatran (0% vs. 88.6%, p = 0.001) and rivaroxaban (0% vs. 79.5%, p = 0.001) were lower in patients with RIDR. However, the underdose rate of apixaban was not different (62.5% vs. 53.9%, p = 0.089). The overdose rate of dabigatran (7.5% vs. 0%) and rivaroxaban (13.7% vs. 0%) was higher in RIDR than in no-RIDR patients. Stroke/transient ischemic attack was significantly higher in CKD patients (1.4 vs. 0.6 per 100 person-years, p = 0.045). Aspirin significantly increased minor bleeding in CKD patients compared with controls (p = 0.037). Conclusion CKD patients might have a high stroke risk and NOAC usage rate. The underdose rate of NOACs decreased in CKD patients, except for apixaban. Aspirin significantly increased minor bleeding in CKD patients.

PURPOSE: Label adherence for non-vitamin K antagonist oral anticoagulants (NOACs) has not been well evaluated in Asian patients with non-valvular atrial fibrillation (AF). The present study aimed to assess label adherence for NOACs in a Korean AF population and to determine risk factors of off-label prescriptions of NOACs. MATERIALS AND METHODS: In this COmparison study of Drugs for symptom control and complication prEvention of AF (CODE-AF) registry, patients with AF who were prescribed NOACs between June 2016 and May 2017 were included. Four NOAC doses were categorized as on- or off-label use according to Korea Food and Drug Regulations. RESULTS: We evaluated 3080 AF patients treated with NOACs (dabigatran 27.2%, rivaroxaban 23.9%, apixaban 36.9%, and edoxaban 12.0%). The mean age was 70.5±9.2 years; 56.0% were men; and the mean CHA₂DS₂-VASc score was 3.3±1.4. Only one-third of the patients (32.7%) was prescribed a standard dose of NOAC. More than one-third of the study population (n=1122, 36.4%) was prescribed an off-label reduced dose of NOAC. Compared to those with an on-label standard dosing, patients with an off-label reduced dose of NOAC were older (≥75 years), women, and had a lower body weight (≤60 kg), renal dysfunction (creatinine clearance ≤50 mL/min), previous stroke, previous bleeding, hypertension, concomitant dronedarone use, and anti-platelet use. CONCLUSION: In real-world practice, more than one-third of patients with NOAC prescriptions received an off-label reduced dose, which could result in an increased risk of stroke. Considering the high risk of stroke in these patients, on-label use of NOAC is recommended.
Anticoagulants ; Asian Continental Ancestry Group ; Atrial Fibrillation ; Body Weight ; Cohort Studies ; Drug and Narcotic Control ; Drug Labeling ; Female ; Hemorrhage ; Humans ; Hypertension ; Korea ; Male ; Off-Label Use ; Prescriptions ; Prospective Studies ; Risk Factors ; Rivaroxaban ; Stroke

PURPOSE: Comparisons of rhythm and rate control strategies for stroke prevention in patients with atrial fibrillation (AF) are still inconclusive. We compared differences in clinical outcomes between the rhythm and rate control strategies. MATERIALS AND METHODS: The COmparison study of Drugs for symptom control and complication prEvention of Atrial Fibrillation (CODE-AF) registry prospectively enrolled 6000 patients who were treated for AF using real-world guideline adherence at multiple referral centers. In total, 2508 (41.8%) patients were clinically followed up for over six months. Of these, 1134 (45.2 %) patients treated by rhythm control and 1374 (54.8 %) patients treated by rate control were analyzed for clinical outcomes, including stroke and cardiovascular outcomes. RESULTS: Among all patients (age, 68±10 years; male, 62.4%), those treated with the rhythm control strategy were significantly younger, had more symptomatic paroxysmal AF, and a shorter AF duration, and were less likely to have diabetes, renal dysfunction, and heart failure, compared to those treated with the rate control strategy (CHA₂DS₂-VASc score 2.4±1.5 vs. 3.1±1.7, p < 0.001). Even though oral anticoagulation was similarly prescribed in both groups, occurrence of stroke was less likely to occur in the rhythm control strategy group (0.0% vs. 0.7%, p=0.015). Multivariate Cox hazard regression showed that only age, especially more than 75 years old, were significantly correlated with the occurrence of stroke, regardless of the strategy used for treatment. CONCLUSION: In this prospective AF cohort, compared with the rate control strategy, the rhythm control strategy was associated with fewer cardiovascular events and strokes in a short-term period.
Administration, Oral ; Aged ; Antithrombins/administration & dosage/therapeutic use ; Atrial Fibrillation/drug therapy/*physiopathology ; Female ; Heart Rate/*physiology ; Humans ; Kaplan-Meier Estimate ; Male ; Proportional Hazards Models ; Prospective Studies ; Stroke/drug therapy/*etiology/*physiopathology ; Treatment Outcome

BACKGROUND AND OBJECTIVES: Gender-related differences in health care utilization for atrial fibrillation (AF) are increasingly recognized. However, large cohort data for examining gender-related differences in AF are lacking in Asian populations. METHODS: The Registry for Comparison Study of Drugs for Symptom Control and Complication Prevention of AF (CODE-AF Registry) is a prospective observational cohort-study that enrolled participants at 10 tertiary hospitals in South Korea. Baseline characteristics retrieved from the CODE-AF Registry were analyzed. RESULTS: A total of 6,274 patients were recruited (mean age 67±11 years, mean CHA2DS2-VASc score 2.7±1.7, 63% male, 65% paroxysmal AF) from June 2016 to April 2017. Women underwent less electric cardioversion (12.3% vs. 19.6%, p < 0.001), less radiofrequency ablation (12.4% vs. 17.9%, p < 0.001), and less antiarrhythmic drug therapy (44.7% vs. 49.5%, p < 0.001), despite having more severe symptoms (symptom class III or IV, 45.8% vs. 37.5%, p < 0.001). Among patients with a CHA2DS2-VA score of 2 or more, a slightly higher proportion of women were taking oral anticoagulants than men (85.7% vs. 81.9%, p=0.002), and non-vitamin K antagonist oral anticoagulant (NOAC) use was more prevalent in women than men (70.4% vs. 62.3%, p < 0.001). Insufficient NOAC dosing was very common, more so in women than men (61.5% vs. 56.3%, p < 0.001). CONCLUSIONS: Female patients with AF were treated more conservatively and rhythm control strategies were used less frequently than in males, even though the female patients with AF had more severe symptoms. While insufficient NOAC dosing was common in both sex, it was significantly more frequent in women.
Anticoagulants ; Asian Continental Ancestry Group ; Atrial Fibrillation ; Catheter Ablation ; Cohort Studies ; Drug Therapy ; Electric Countershock ; Female ; Humans ; Korea ; Male ; Patient Acceptance of Health Care ; Prospective Studies ; Registries ; Sex Characteristics ; Tertiary Care Centers

BACKGROUND AND OBJECTIVES: Gender-related differences in health care utilization for atrial fibrillation (AF) are increasingly recognized. However, large cohort data for examining gender-related differences in AF are lacking in Asian populations. METHODS: The Registry for Comparison Study of Drugs for Symptom Control and Complication Prevention of AF (CODE-AF Registry) is a prospective observational cohort-study that enrolled participants at 10 tertiary hospitals in South Korea. Baseline characteristics retrieved from the CODE-AF Registry were analyzed. RESULTS: A total of 6,274 patients were recruited (mean age 67±11 years, mean CHA2DS2-VASc score 2.7±1.7, 63% male, 65% paroxysmal AF) from June 2016 to April 2017. Women underwent less electric cardioversion (12.3% vs. 19.6%, p < 0.001), less radiofrequency ablation (12.4% vs. 17.9%, p < 0.001), and less antiarrhythmic drug therapy (44.7% vs. 49.5%, p < 0.001), despite having more severe symptoms (symptom class III or IV, 45.8% vs. 37.5%, p < 0.001). Among patients with a CHA2DS2-VA score of 2 or more, a slightly higher proportion of women were taking oral anticoagulants than men (85.7% vs. 81.9%, p=0.002), and non-vitamin K antagonist oral anticoagulant (NOAC) use was more prevalent in women than men (70.4% vs. 62.3%, p < 0.001). Insufficient NOAC dosing was very common, more so in women than men (61.5% vs. 56.3%, p < 0.001). CONCLUSIONS Female patients with AF were treated more conservatively and rhythm control strategies were used less frequently than in males, even though the female patients with AF had more severe symptoms. While insufficient NOAC dosing was common in both sex, it was significantly more frequent in women.

BACKGROUND AND OBJECTIVES: The aging population is rapidly increasing, and atrial fibrillation (AF) is becoming a significant public health burden in Asia, including Korea. This study evaluated current treatment patterns and guideline adherence of AF treatment. METHODS: In a prospective observational registry (COmparison study of Drugs for symptom control and complication prEvention of Atrial Fibrillation [CODE-AF] registry), 6,275 patients with nonvalvular AF were consecutively enrolled between June 2016 and April 2017 from 10 tertiary hospitals in Korea. RESULTS: The AF type was paroxysmal, persistent, and permanent in 65.3%, 30.0%, and 2.9% of patients, respectively. Underlying structural heart disease was present in 11.9%. Mean CHA2DS2-VASc was 2.7±1.7. Oral anticoagulation (OAC), rate control, and rhythm control were used in 70.1%, 53.9%, and 54.4% of patients, respectively. OAC was performed in 82.7% of patients with a high stroke risk. However, antithrombotic therapy was inadequately used in 53.4% of patients with a low stroke risk. For rate control in 192 patients with low ejection fraction (< 40%), β-blocker (65.6%), digoxin (5.2%), or both (19.3%) were adequately used in 90.1% of patients; however, a calcium channel blocker was inadequately used in 9.9%. A rhythm control strategy was chosen in 54.4% of patients. The prescribing rate of class Ic antiarrythmics, dronedarone, and sotalol was 16.9% of patients with low ejection fraction. CONCLUSION: This study shows how successfully guidelines can be applied in the real world. The nonadherence rate was 17.2%, 9.9%, and 22.4% for stroke prevention, rate control, and rhythm control, respectively.
Aging ; Asia ; Atrial Fibrillation* ; Calcium Channels ; Digoxin ; Guideline Adherence* ; Heart Diseases ; Humans ; Korea ; Prospective Studies* ; Public Health ; Sotalol ; Stroke ; Tertiary Care Centers