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

PURPOSE: Patients treated with propranolol, a nonselective β-adrenoceptor antagonist, develop severe anaphylaxis, but the mechanism remains unknown. We determined effects of β₁- and β₂-adrenoceptor antagonists on the anaphylaxis-induced increase in vascular permeability in mice. METHODS: In anesthetized ovalbumin-sensitized C57BL mice, mean arterial blood pressure (MBP) was measured, and Evans blue dye extravasation and hematocrit (Hct) were assessed at 20 minutes after antigen injection. The following pretreatment groups (n=7/group) were studied: (1) sensitized control (non-pretreatment), (2) propranolol, (3) the selective β₂-adrenoceptor antagonist ICI 118,551, (4) the selective β₁-adrenoceptor antagonist atenolol, (5) adrenalectomy, (6) the selective β₂-adrenoceptor agonist terbutaline, and (7) non-sensitized groups. RESULTS: The antigen injection decreased MBP, and increased Hct and vascular permeability in the kidney, lung, mesentery, and intestine, but not in the liver or spleen. Pretreatment with ICI 118,551, propranolol and adrenalectomy, but not atenolol, reduced the survival rate and augmented the increases in Hct and vascular permeability in the kidney, intestine, and lung as compared with the sensitized control group. Pretreatment with terbutaline abolished the antigen-induced alterations. Plasma epinephrine levels were increased significantly in the sensitize control mice. CONCLUSIONS: Blockade of β₂-adrenoceptor can deteriorate systemic anaphylaxis by augmenting hyperpermeability-induced increase in plasma extravasation by inhibiting beneficial effects of epinephrine released from the adrenal glands in anesthetized mice.
Adrenal Glands ; Adrenalectomy ; Anaphylaxis ; Animals ; Arterial Pressure ; Atenolol ; Capillary Permeability ; Epinephrine ; Evans Blue ; Hematocrit ; Humans ; Intestines ; Kidney ; Liver ; Lung ; Mesentery ; Mice ; Mice, Inbred C57BL ; Plasma ; Propranolol ; Spleen ; Survival Rate ; Terbutaline

PURPOSE: The aim of this study was to evaluate the effects of premedication with oral atenolol or enalapril, in combination with remifentanil under sevoflurane anesthesia, on intraoperative blood loss by achieving adequate deliberate hypotension (DH) during orthognathic surgery. Furthermore, we investigated the impact thereof on the amount of nitroglycerin (NTG) administered as an adjuvant agent. MATERIALS AND METHODS: Seventy-three patients undergoing orthognathic surgery were randomly allocated into one of three groups: an angiotensin converting enzyme inhibitor group (Group A, n=24) with enalapril 10 mg, a beta blocker group (Group B, n=24) with atenolol 25 mg, or a control group (Group C, n=25) with placebo. All patients were premedicated orally 1 h before the induction of anesthesia. NTG was the only adjuvant agent used to achieve DH when mean arterial blood pressure (MAP) was not controlled, despite the administration of the maximum remifentanil dose (0.3 microg kg-1min-1) with sevoflurane. RESULTS: Seventy-two patients completed the study. Blood loss was significantly reduced in Group A, compared to Group C (adjusted p=0.045). Over the target range of MAP percentage during DH was significantly higher in Group C than in Groups A and B (adjusted p-values=0.007 and 0.006, respectively). The total amount of NTG administered was significantly less in Group A than Group C (adjusted p=0.015). CONCLUSION: Premedication with enalapril (10 mg) combined with remifentanil under sevoflurane anesthesia attenuated blood loss and achieved satisfactory DH during orthognathic surgery. Furthermore, the amount of NTG was reduced during the surgery.
Administration, Oral ; Adrenergic beta-Antagonists/administration & dosage/*pharmacology ; Adult ; Aged ; *Anesthesia, Inhalation ; Atenolol/administration & dosage/*pharmacology ; Blood Loss, Surgical ; Blood Pressure/drug effects ; Cardiac Output/drug effects ; Double-Blind Method ; Enalapril/administration & dosage/*pharmacology ; Female ; Heart Rate/drug effects ; Humans ; Intraoperative Care ; Male ; Methyl Ethers/*administration & dosage ; Middle Aged ; *Orthognathic Surgical Procedures ; Piperidines/*administration & dosage ; *Premedication ; Treatment Outcome

A 15-year-old adolescent with unilateral multiple adrenal pheochromocytoma had an episode of subcortical intracerebral hemorrhage and seizure 6 weeks before the surgery. He was pretreated with terazosin, losartan, atenolol and levetiracetam for 2 weeks. Dexmedetomidine was started in the preoperative waiting area, and a combination of dexmedetomidine and remifentanil was continuously infused for most of anesthetic time. To control blood pressure, bolus injection of remifentanil and low-dose infusion of sodium nitroprusside, nicardipine, and esmolol were administered during three adrenergic crises. There was minimal post-resection hypotension, and his trachea was extubated safely 20 min after the surgery. He was discharged without noticeable complication. His catecholamine levels showed the steadily decreasing pattern during the operation in this case. Though a combination of dexmedetomidine and remifentanil may not prevent the hemodynamic instability impeccably during the tumor manipulation, this combination seems to be the way of interrupting release of catecholamines and minimizing hemodynamic fluctuations.
Adolescent ; Atenolol ; Blood Pressure ; Catecholamines ; Cerebral Hemorrhage ; Dexmedetomidine ; Hemodynamics ; Humans ; Hypotension ; Losartan ; Nicardipine ; Nitroprusside ; Pheochromocytoma ; Piperidines ; Piracetam ; Prazosin ; Propanolamines ; Seizures ; Trachea

beta -Blockers can cause bronchospasm in asthma. beta 2-agonists prolong the QT interval and alter the clinical course of long QT syndrome (LQTS). We report a case of asthma exacerbation treated cautiously with beta 2-agonists in a patient with LQTS, while LQTS was controlled with low-dose beta 1-antagonists. A 31-year-old woman with LQTS visited the emergency room for asthma exacerbation. FEV1 was 0.5 L (18%) and QTc interval was 520 ms. Low doses of salbutamol or salmeterol were used and gradually increased, while monitoring the QT interval. Simultaneously, a low dose of atenolol was maintained. FEV1 was increased to 2.2 L (83%) without further QT prolongation or cardiac events. The case suggests that lower doses of beta 1-antagonists can be tried for cardiac diseases, even in the presence of asthma exacerbations. beta 2-Agonists may be initiated at lower doses and, if tolerated, the dose can be increased in asthmatic patients with a risk for QT prolongation.
Adrenergic beta-Agonists ; Adrenergic beta-Antagonists ; Adult ; Albuterol ; Asthma ; Atenolol ; Bronchial Spasm ; Emergencies ; Female ; Heart Diseases ; Humans ; Long QT Syndrome ; Salmeterol Xinafoate

Chronic treatment with renin-angiotensin system antagonists frequently causes deleterious hypotension during anesthesia. We present a case of marked intra-operative refractory hypotension in a 61-year-old male patient undergoing elective total thyroidectomy. He has been chronically treated for hypertension with angiotensin-converting enzyme inhibitors, angiotensin II receptor antagonists and atenolol, which were taken until the morning of surgery. After induction of anesthesia, marked hypotension which was refractory to fluid therapy occurred and did not respond to ephedrine administration. After continuous norepinephrine infusion, blood pressure increased and remained stable during the anesthesia period. Before extubation, norepinephrine was discontinued and recovery took place without complications. We discuss the anesthetic implication of chronic renin-angiotensin system antagonists treatment and intra-operative hemodynamic instability.
Anesthesia ; Angiotensin Receptor Antagonists ; Angiotensin-Converting Enzyme Inhibitors ; Atenolol ; Blood Pressure ; Ephedrine ; Fluid Therapy ; Hemodynamics ; Humans ; Hypertension ; Hypogonadism ; Hypotension ; Male ; Middle Aged ; Mitochondrial Diseases ; Norepinephrine ; Ophthalmoplegia ; Renin-Angiotensin System ; Thyroidectomy

OBJECTIVETo compare the beneficial effects of Atenolol and Metoprolol on cardiomyocyte apoptosis and related gene expressions after acute myocardial infarction (AMI) in rats.

METHODSAMI model was established with the ligation of anterior descending coronary artery in 251 randomly selected female SD rats. Twenty-four hours after operation, the 124 survivors were randomly assigned to AMI control group (MI group, n = 43), Atenolol group (group A, 10 mg x kg(-1) d(-1), n = 39), and Metoprolol group (group B, 20 mg x kg(-1) x d(-1), n = 42). Sham operation group (group S, n = 27) was also established. Two subgroup (48 h subgroup and 4 weeks subgroup) was randomly divided in each group according to the time points. Drugs were given to each treatment group by gastric gavage 24 h after ligation. Cardiomyocyte apoptosis was detected with terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL) and DNA ladder. Bcl-2, bax and caspase-3 genes were detected with immunohistochemistry and Western blot analysis.

RESULTSCompared with AMI control group, myocyte apoptosis rate (MAR) significantly decreased only in infarction area (P < 0.01) in group B. Bcl-2 expression was found to increase in myocytes of infarction, border and non-infarcted areas except for non-infarcted area of group A. Changes of the expressions of bax and caspase-3 was not significant. Four weeks after AMI, MAR was found to decrease significantly in scar, border and non-infarcted areas (P < 0.05, P < 0.01) in both group A and group B. No significant changes of bcl-2, bax and caspase-3 expressions was found except for a significant decrease of bax expression in non-infarcted area of group A. As indicated by Western blot, no significant change of the expressions of caspase-3, bcl-2 and bax were found in myocytes of group A and group B compared with AMI control group; however, bcl-2/bax ratio significantly increased to the same level of sham-operated group (P < 0.05).

CONCLUSIONBoth Atenolol and Metoprolol treatment can reduce cardiomyocyte apoptosis in infarction/scar, border and non-infarcted areas after AMI, mainly through the increase of bcl-2 expression and bcl-2/bax ratio.

Adrenergic beta-Antagonists ; pharmacology ; Animals ; Apoptosis ; drug effects ; Atenolol ; pharmacology ; Female ; Metoprolol ; pharmacology ; Myocardial Infarction ; pathology ; Myocytes, Cardiac ; pathology ; Proto-Oncogene Proteins c-bcl-2 ; biosynthesis ; genetics ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; bcl-2-Associated X Protein ; biosynthesis ; genetics

AIMThe simplified preparative method and formulation for atenolol monolithic osmotic pump tablets were investigated.

METHODSThe core tablets with an indentation were compressed by the punch with a needle. Osmotic pump tablets were prepared by coating the indented tablets. Similarity factor was used to evaluate formulation of osmotic pump tablets.

RESULTSThe formulation of core tablets and the composition and thickness of coating membrane showed marked effects on drug release. Orifice size of core tablets in the range of 1.00 - 1.14 mm scarcely affected drug release.

CONCLUSIONThe preparation of osmotic pump tablets was simplified with the exempting of laser drilling. The atenolol monolithic osmotic pump tablets could deliver drug constantly for 24 h.

Adrenergic beta-Antagonists ; administration & dosage ; chemistry ; Atenolol ; administration & dosage ; chemistry ; Delayed-Action Preparations ; Drug Carriers ; Osmosis ; Polyethylene Glycols ; chemistry ; Tablets ; Technology, Pharmaceutical ; methods

BACKGROUND: Carvedilol is a direct inhibitor of vascular smooth muscle cell migration and proliferation through inhibition of mitogen-activated protein kinase activity and regulation of cell cycle progression. It produced an 84% suppression of neointimal hyperplasia in rat carotid angioplasty model, but no data are available regarding its effect on stent restenosis in patients. We tested whether a sustained oral administration of carvedilol reduces restenosis after coronary stenting in patients. METHODS: One hundred fifty nine patients were randomized to receive either carvedilol (50 mg/day, n=80) or atenolol (50 mg/day, n=79) at least 1 day before stenting and continued on the same medication over 3 months. The primary end point was angiographic restenosis (>50% diameter stenosis) at follow-up angiography. RESULTS: Baseline clinical and angiographic variables were similar between the carvedilol and atenolol group. The carvedilol dose was tolerable in most patients after adjustment of other medications, but reduced in 3 patients due to hypotension and dizziness. Angiographic follow-up was done in 137 patients (86%) and the restenosis rate was not different significantly between both groups (17.1% versus 19.4%, p=0.732). CONCLUSION: A sustained oral administration of carvedilol is not effective to reduce stent restenosis. With carvedilol targeting regulators of cell cycle progression and having a profound neointimal inhibition with a high blood concentration in an experiment, further investigations using a stent-based delivery to achieve a high local concentration may be warranted.
Administration, Oral ; Angiography ; Angioplasty ; Animals ; Atenolol ; Cell Cycle ; Cell Movement ; Coronary Restenosis ; Dizziness ; Drug Therapy ; Follow-Up Studies ; Humans ; Hyperplasia ; Hypotension ; Muscle, Smooth, Vascular ; Prospective Studies* ; Protein Kinases ; Rats ; Stents*

BACKGROUND: Alterations of mechanical properties in the vasculature may contribute to complications of hypertension. Since angiotensin II plays a pivotal role in these vascular abnormalities, we tested the hypothesis that the AT1 angiotensin receptor antagonist irbesartan, in contrast to the beta-blocker atenolol, would correct artery stiffness in essential hypertensive patients. METHODS: Thirty untreated essential hypertensive patients (48 +/- 7 years, range 35-65; 72% male) were randomly assigned in a single-blind fashion to irbesartan or atenolol treatment for 6 months. Fifty one age/sex-matched normotensive subjects were also studied. Systemic arterial stiffness (augmentation index; AI) was measured by the pressure transfer function using radial pulse tonometry. RESULTS: Both treatments reduced blood pressure (BP) to a comparable degree (irbesartan: 160 +/- 19/105 +/- 13 to 133 +/- 16/92 +/- 10 mmHg, p<0.01; atenolol: 166 +/- 17/113 +/- 9 to 132 +/- 15/90 +/- 8 mmHg, p<0.01). Other hemodynamic parameters of peripheral and central arteries showed similar degree of reduction, except significant reduction of central pulse pressure with irbesartan treatment (42 +/- 20 to 29 +/- 8 mmHg, p=0.01 vs 41 +/- 14 to 34 +/- 12 mmHg of atenolol treatment). After 6-month treatment, systemic arterial stiffness (AI) was significantly reduced from 28 +/- 11 to 21 +/- 11% (p=0.01) after irbesartan but atenolol treatment showed no change (from 29 +/- 8 to 29 +/- 13%). Reversal of arterial stiffness correlated mostly with reduction of central pulse pressure (r=0.63, p<0.01). CONCLUSION: The AT1 angiotensin antagonist irbesartan corrected the altered arterial stiffness from patients with essential hypertension by reduction of central pulse pressure, whereas the beta-blocker atenolol had no effect.
Angiotensin II ; Angiotensins* ; Arteries ; Atenolol ; Blood Pressure ; Hemodynamics ; Humans ; Hypertension* ; Manometry ; Receptors, Angiotensin ; Vascular Stiffness*