PURPOSE: Although the economic and mortality burden of atrial fibrillation (AF) is substantial, it remains unclear which treatment strategies for rate and rhythm control are most cost-effective. Consequently, economic factors can play an adjunctive role in guiding treatment selection. MATERIALS AND METHODS: We built a Markov chain Monte Carlo model using the Korean Health Insurance Review & Assessment Service database. Drugs for rate control and rhythm control in AF were analyzed. Cost-effective therapies were selected using a cost-effectiveness ratio, calculated by net cost and quality-adjusted life years (QALY). RESULTS: In the National Health Insurance Service data, 268149 patients with prevalent AF (age ≥18 years) were identified between January 1, 2013 and December 31, 2015. Among them, 212459 and 55690 patients were taking drugs for rate and rhythm control, respectively. Atenolol cost $714/QALY. Among the rate-control medications, the cost of propranolol was lowest at $487/QALY, while that of carvedilol was highest at $1363/QALY. Among the rhythm-control medications, the cost of pilsicainide was lowest at $638/QALY, while that of amiodarone was highest at $986/QALY. Flecainide and propafenone cost $834 and $830/QALY, respectively. The cost-effectiveness threshold of all drugs was lower than $30000/QALY. Compared with atenolol, the rate-control drugs propranolol, betaxolol, bevantolol, bisoprolol, diltiazem, and verapamil, as well as the rhythm-control drugs sotalol, pilsicainide, flecainide, propafenone, and dronedarone, showed better incremental cost-effectiveness ratios. CONCLUSION: Propranolol and pilsicainide appear to be cost-effective in patients with AF in Korea assuming that drug usage or compliance is the same.
Amiodarone ; Atenolol ; Atrial Fibrillation ; Betaxolol ; Bisoprolol ; Compliance ; Cost-Benefit Analysis ; Diltiazem ; Flecainide ; Humans ; Insurance, Health ; Korea ; Markov Chains ; Mortality ; National Health Programs ; Propafenone ; Propranolol ; Quality-Adjusted Life Years ; Sotalol ; Verapamil

Although the benefits of carvedilol have been demonstrated in the era of percutaneous coronary intervention (PCI), very few studies have evaluated the efficacy of bisoprolol in the secondary prevention of acute myocardial infarction (MI) in patients treated with PCI. We hypothesized that the effect of bisoprolol would not be different from carvedilol in post-MI patients. A total of 13,813 patients who underwent PCI were treated either with carvedilol or bisoprolol at the time of discharge. They were enrolled from the Korean Acute MI Registry (KAMIR). After 1:2 propensity score matching, 1,806 patients were enrolled in the bisoprolol group and 3,612 patients in the carvedilol group. The primary end point was the composite of major adverse cardiac events (MACEs), which was defined as cardiac death, nonfatal MI, target vessel revascularization, and coronary artery bypass surgery. The secondary end point was defined as all-cause mortality, cardiac death, nonfatal MI, any revascularization, or target vessel revascularization. After adjustment for differences in baseline characteristics by propensity score matching, the MACE-free survival rate was not different between the groups (HR=0.815, 95% CI:0.614–1.081, p=0.156). In the subgroup analysis, the cumulative incidence of MACEs was lower in the bisoprolol group in patients having a Killip class of III or IV than in the carvedilol group (HR=0.512, 95% CI: 0.263–0.998, p=0.049). The incidence of secondary end points was similar between the two beta-blocker groups. In conclusion, the benefits of bisoprolol were comparable with those of carvedilol in the secondary prevention of acute MI.
Bisoprolol* ; Coronary Artery Bypass ; Death ; Humans ; Incidence ; Mortality ; Myocardial Infarction* ; Percutaneous Coronary Intervention* ; Propensity Score ; Secondary Prevention* ; Survival Rate

BACKGROUND: We aimed to evaluate effect of heart rate (HR) reduction on left ventricular reverse remodeling (LVRR) in Korean patients with heart failure with reduced ejection fraction (HFrEF). METHODS: Ambulatory patients with HFrEF, who had paired echocardiograms, N-terminal prohormone brain natriuretic peptide (NT-proBNP), and global assessment score (GAS) at baseline and 6-month (n = 157), were followed up on preset treatment schedule with bisoprolol. RESULTS: The LVRR occurred in 49 patients (32%) at 6-month. In multivariable analysis, independent predictors associated with LVRR were use of anti-aldosterone agent (odds ratio [OR], 4.18; 95% confidence interval [CI], 1.80–9.71), young age (OR, 0.96; 95% CI, 0.92–0.99), high baseline HR (OR, 3.76; 95% CI, 1.40–10.10), and favorable baseline GAS (OR, 1.73; 95% CI, 1.06–2.81). Beneficial effect of bisoprolol, in terms of LVRR, NT-proBNP, and GAS, was remarkable in the high HR group (baseline HR ≥ 75 beats per minute [bpm]), which showed a large HR reduction. CONCLUSION: High baseline HR (≥ 75 bpm) showed an association with LVRR and improvement of NT-proBNP and GAS in patients with HFrEF. This seems to be due to a large HR reduction after treatments with bisoprolol. Trial registry at www.ClinicalTrials.gov, NCT00749034.
Appointments and Schedules ; Bisoprolol* ; Heart Failure ; Heart Rate* ; Heart* ; Humans ; Natriuretic Peptide, Brain

BACKGROUND: In the rural environment, medicine treatment has analyzed the health behavior of some rural areas, but it is necessary to study and generalize trends of interest in the whole country. Therefore, The objective of this study is to analyze interest trends of rural health care services of rural residents in rural areas by Big Data.METHODS: Big medical data collection related to rural environment medicine treatment used portal site data of social networks. The Big Data was analyzed utilizing a Textom and Ucinet6 analysis tools.RESULTS: Among the major keywords of Big Data are ‘hospital’, ‘university’, ‘management’, ‘seat’, ‘improvement’, ‘residents’, ‘information’, ‘exercise’, ‘development’, ‘problem’, ‘Pain’, ‘Possibility’, ‘Post’, ‘Work’, ‘Relationship’ etc occupy a high rank in all analyzes such as frequency ranking, total network analysis, 4 centrality and CONCOR analysis. In rural environment medicine, the individual diseases of interest were skin, scars, atopy, acne, eyes, hyperlipidemia, stress and so on. It is also possible to find out whether the program, the longevity person, the cultivation, the village, the farm, the activity, the program, the education, the experience, etc.CONCLUSION: In the rural areas, they are interested in the folk medicine that can be used in the rural areas for the treatment of the diseases related to the rural areas.The lack of treatment for children and women indicated that professional information was needed, and they also expressed interest in food, life, and spatial location for long-lived villages. Specially, “atopy” and “earnestness” were included in the main words. The word ‘health center’, which is the subject of various health promotion projects, was not included in the 170 main words.
Acne Vulgaris ; Agriculture ; Bisoprolol ; Child ; Cicatrix ; Data Collection ; Education ; Female ; Health Behavior ; Health Promotion ; Humans ; Hyperlipidemias ; Longevity ; Medicine, Traditional ; Rural Health ; Skin

BACKGROUND: Patients with acute ischemic stroke are susceptible  to  cardiac  arrhythmias  however,fatal arrhythmias  are  rare  in  the  absence  of  cardiac  disease.Cardiac arrhythmias can develop in lesions at the right side of the brain specifically the insular,frontal and parietal area.Data that show the direct relationship of ischemic stroke and arrhythmia are scarce but they are indirectly attributed to an imbalance in the autonomic nervous system.This paper aims to present a rare case of an association between a fatal arrhythmia and right thalamic infarct.  
CASE: Presenting a case of a 39-year-old admitted as a survivor of sudden cardiac death from ventricular fibrillation.She presented with a history of left sided weakness a week prior but no work-up was done. Baseline serum electrolytes and  cardiac markers were all normal.Electrocardiogram (ECG) post-cardioversion showed sinus tachycardia.Echocardiogram   and cardiac computed tomography (CT) angiography were normal.  Magnetic resonance imaging (MRI) and angiography (MRA) of the brain showed an acute infarct at the right thalamus and an absent left internal carotid artery (ICA).Electroencephalogram (EEG) was negative.Bisoprolol was given and an Automatic Implantable Cardioverter Defibrillator (AICD) was subsequently placed.No recurrence of cardiac arrhythmia was noted on continuous cardiac telemetry monitoring during her hospitalization and on six months of follow-up.
CONCLUSION: Fatal cardiac arrhythmias, can occur in patients with  acute  thalamic  infarct  even  beyond  24  hours  in  the presence of other confounding factors despite the absence of cardiac pathology. This case showed the association of heightened  autonomic  imbalance  caused  by  an  acute stroke, decreased cerebral flow, and fatal arrhythmia. This elucidates the importance of cardiac monitoring in acute ischemic stroke. With the paucity of information on serious cardiac arrhythmia and ischemic stroke, a future study on this correlation will be useful.

Human ; Female ; Adult ; Bisoprolol ; Tachycardia, Sinus ; Ventricular Fibrillation ; Carotid Artery, Internal ; Defibrillators, Implantable ; Electric Countershock ; Arrhythmias, Cardiac ; Electrocardiography ; Death, Sudden, Cardiac ; Heart Conduction System ; Stroke ; Thalamus ; Brain ; Autonomic Nervous System ; Telemetry ; Angiography ; Hospitalization ; Survivors ; Electrolytes

BACKGROUND/AIMS: We evaluated the association between coding region variants of adrenergic receptor genes and therapeutic effect in patients with congestive heart failure (CHF). METHODS: One hundred patients with stable CHF (left ventricular ejection fraction [LVEF] < 45%) were enrolled. Enrolled patients started 1.25 mg bisoprolol treatment once daily, then up-titrated to the maximally tolerable dose, at which they were treated for 1 year. RESULTS: Genotypic analysis was carried out, but the results were blinded to the investigators throughout the study period. At position 389 of the beta-1 adrenergic receptor gene (ADRB1), the observed minor Gly allele frequency (Gly389Arg + Gly389Gly) was 0.21, and no deviation from Hardy-Weinberg equilibrium was observed in the genotypic distribution of Arg389Gly (p = 0.75). Heart rate was reduced from 80.8 +/- 14.3 to 70.0 +/- 15.0 beats per minute (p < 0.0001). There was no significant difference in final heart rate across genotypes. However, the Arg389Arg genotype group required significantly more bisoprolol compared to the Gly389X (Gly389Arg + Gly389Gly) group (5.26 +/- 2.62 mg vs. 3.96 +/- 2.05 mg, p = 0.022). There were no significant differences in LVEF changes or remodeling between two groups. Also, changes in exercise capacity and brain natriuretic peptide level were not significant. However, interestingly, there was a two-fold higher rate of readmission (21.2% vs. 10.0%, p = 0.162) and one CHF-related death in the Arg389Arg group. CONCLUSIONS: The ADRB1 Gly389X genotype showed greater response to bisoprolol than the Arg389Arg genotype, suggesting the potential of individually tailoring beta-blocker therapy according to genotype.
Adrenergic beta-1 Receptor Antagonists/adverse effects/*therapeutic use ; Adult ; Aged ; Bisoprolol/adverse effects/*therapeutic use ; Female ; Gene Frequency ; Genotype ; Heart Failure/diagnosis/*drug therapy/*genetics/physiopathology ; Heart Rate/drug effects ; Humans ; Male ; Maximum Tolerated Dose ; Middle Aged ; Pharmacogenomic Testing ; Phenotype ; *Polymorphism, Genetic ; Precision Medicine ; Receptors, Adrenergic, beta-1/*drug effects/*genetics ; Republic of Korea ; Stroke Volume/drug effects ; Time Factors ; Treatment Outcome ; Ventricular Function, Left/drug effects ; Ventricular Remodeling/drug effects

Use of oral hypoglycemic agents during pregnant women with type 2 diabetes is controversial due to safety issues. Recently, randomized controlled trials support short-term safety of glyburide and metformin for the treatment of gestational diabetes mellitus. However, long-term safety data are not available. Moreover, use of oral hypoglycemic agents, except for metformin and glyburide, during pregnancy were limited to a few case reports. We report the case of a pregnant woman with type 2 diabetes unintentionally exposed to metformin and voglibose in addition to lercanidipine and bisoprolol during fetal organogenesis. The patient was continuously exposed to oral agents because we were not aware of her pregnancy until 22 weeks of gestation. After pregnancy was confirmed, we replaced oral hypoglycemic agents with insulin and discontinue betablockers. Delivery occurred without maternal or fetal complications.
Bisoprolol ; Diabetes, Gestational ; Female ; Glyburide ; Humans ; Hypoglycemic Agents ; Insulin ; Metformin* ; Organogenesis ; Pregnancy ; Pregnancy Trimester, Second* ; Pregnancy* ; Pregnant Women*

Stevens-Johnson syndrome (SJS) manifests with severe cutaneous reactions, most commonly triggered by medications, which are characterized by fever and mucocutaneous lesions leading to necrosis and sloughing of the epidermis. To our knowledge, pravastatin-induced SJS has not yet been reported. Here, we describe a case of SJS due to pravastatin, which was diagnosed by a patch test. A 70-year-old woman presented with maculopapular skin rashes, which developed 2 weeks after medication of bisoprolol, amlodipine, pravastatin, spironolactone, and indobufene for cardiac problems. Various bullous-erosive mucocutaneous lesions occupied less than 10% of the total body surface area. Painful oropharyngeal mucous membrane lesions were observed. The vermilion border of the lips became denuded and developed serosanguinous crusts. With the drug withdrawal and the use of systemic corticosteroids, her manifestations resolved. Drug patch tests with bisoprolol, amlodipine, pravastatin, spironolactone, and indobufene were performed, resulting in a positive reaction to pravastatin, but not to the other drugs. To the best of our knowledge, this is the first case of pravastatin-induced SJS.
Adrenal Cortex Hormones ; Aged ; Amlodipine ; Bisoprolol ; Body Surface Area ; Epidermis ; Exanthema ; Female ; Fever ; Humans ; Lip ; Mucous Membrane ; Necrosis ; Patch Tests ; Pravastatin ; Spironolactone ; Stevens-Johnson Syndrome*

Aspirin ; therapeutic use ; Bisoprolol ; therapeutic use ; Cardiomyopathies ; chemically induced ; etiology ; Cardiotonic Agents ; adverse effects ; Chest Pain ; diagnostic imaging ; Dobutamine ; adverse effects ; Echocardiography, Stress ; adverse effects ; Enalapril ; therapeutic use ; Humans ; Male ; Middle Aged ; Simvastatin ; therapeutic use

OBJECTIVEThe purpose of this study was to investigate the relation between the Arg389Gly polymorphism of the beta(1)-AR gene and chronic heart failure (CHF) and to evaluate the effect of this polymorphism on clinical response to beta-adrenoceptor blockade (bisoprolol) in patients with CHF.

METHODSOne hundred and ten patients with stable CHF receiving basic therapy for heart failure were included. Before initiation and 3 months after the maximal tolerated dose of bisoprolol was reached, all indices (including BP, HR, LAD, LVEDD, LVESD, LVEF, BNP level, 6 min walk distance) were measured and compared with the Arg389Gly genotypes, which identified by PCR-restriction fragment length polymorphism analysis. We also determined the Arg389Gly genotypes in 100 healthy control subjects, and compared the distribution of Arg389Gly genotypes with that in CHF.

RESULTSNo difference was observed between the two groups in any of the three genotypes (CC, CG and GG). The prevalences of the three genotypes in normal subjects and patients with CHF were Arg389Arg 0.53 vs. 0.51, Arg389Gly 0.40 vs. 0.40, Gly38Gly 0.07 vs. 0.09, respectively. After 3 months of bisoprolol usage, a significant improvement in LVEF was observed in CC group, which increased from (36.7 +/- 8.63)% to (44.1 +/- 9.53)%, CG group, from (35.76 +/- 8.39)% to (42.90 +/- 9.41)%, but not GG group, from (36.00 +/- 5.66)% to (37.33 +/- 5.64)%. The improvement in BNP was also observed in CC [from (502.93 +/- 160.80) ng/L to (325.26 +/- 135.63) ng/L], CG [from (525.76 +/- 157.66) ng/L to (331.79 +/- 133.97) ng/L], but not GG [from (505.33 +/- 125.07) ng/L to (429.67 +/- 182.39) ng/L]. Arg389-homozygous patients showed a substantially greater improvement in LVEF and BNP, compared with Gly389-homozygous patients (all P < 0.01).

CONCLUSIONSThere was no difference in the prevalence of the three genotypes between healthy and CHF subjects. The Gly389 polymorphism of the beta(1)-AR gene was not associated with an increased risk of CHF. The Arg389 variant of the beta(1)-AR gene was associated with a greater response to bisoprolol than that of the Gly389 variant in patients with CHF.

Adrenergic beta-Antagonists ; therapeutic use ; Adult ; Aged ; Aged, 80 and over ; Bisoprolol ; therapeutic use ; Case-Control Studies ; Female ; Follow-Up Studies ; Heart Failure ; drug therapy ; genetics ; physiopathology ; Humans ; Male ; Middle Aged ; Natriuretic Peptide, Brain ; blood ; Polymorphism, Genetic ; Receptors, Adrenergic, beta-1 ; genetics