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1.
Carvedilol versus propranolol effect on hepatic venous pressure gradient at 1 month in patients with index variceal bleed: RCT.
Gupta, V, Rawat, R, Shalimar, , Saraya, A
Hepatology international. 2017;(2):181-187
Abstract
BACKGROUND AND AIMS Endoscopic variceal ligation (EVL) plus beta blocker is the mainstay treatment after index bleed to prevent rebleed. Primary objective of this study was to compare EVL plus propranolol versus EVL plus carvedilol on reduction of HVPG after 1 month of therapy. METHODS Patients of cirrhosis presenting with index esophageal variceal bleed received standard treatment (Somatostatin therapy f/b EVL) following which HVPG was measured and patients were randomized to propranolol or carvedilol group if HVPG was >12 mmHg. Standard endotherapy protocol was continued in both groups. HVPG was again measured at 1 month of treatment. RESULTS Out of 129 patients of index esophageal variceal bleed, 59 patients were eligible and randomized into carvedilol (n = 30) and propranolol (n = 29). At 1 month of treatment, decrease in heart rate, mean arterial blood pressure (MAP) and HVPG was significant within each group (p = 0.001). Percentage decrease in MAP was significantly more in carvedilol group as compared to propranolol group (p = 0.04). Number of HVPG responders (HVPG decrease >20 % or below 12 mmHg) was significantly more in carvedilol group (22/29) as compared to propranolol group (14/28), p = 0.04. CONCLUSION Carvedilol is more effective in reducing portal pressure in patients with cirrhosis with esophageal bleed. Though a larger study is required to substantiate this, the results in this study are promising for carvedilol. Clinical trials online government registry (CTRI/2013/10/004119). Trial registration number CTRI/2013/10/004119.
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2.
Randomized Control of Sympathetic Drive With Continuous Intravenous Esmolol in Patients With Acute ST-Segment Elevation Myocardial Infarction: The BEtA-Blocker Therapy in Acute Myocardial Infarction (BEAT-AMI) Trial.
Er, F, Dahlem, KM, Nia, AM, Erdmann, E, Waltenberger, J, Hellmich, M, Kuhr, K, Le, MT, Herrfurth, T, Taghiyev, Z, et al
JACC. Cardiovascular interventions. 2016;(3):231-240
Abstract
OBJECTIVES This study sought to evaluate the role of esmolol-induced tight sympathetic control in patients with ST-segment elevation myocardial infarction (STEMI). BACKGROUND Elevated sympathetic drive has a detrimental effect on patients with acute STEMI. The effect of beta-blocker-induced heart rate mediated sympathetic control on myocardial damage is unknown. METHODS The authors conducted a prospective, randomized, single-blind trial involving patients with STEMI and successful percutaneous intervention (Killip class I and II). Patients were randomly allocated to heart rate control with intravenous esmolol for 24 h or placebo. The primary outcome was the maximum change in troponin T release as a prognostic surrogate marker for myocardial damage. A total of 101 patients were enrolled in the study. RESULTS There was a significant difference between patients allocated to placebo and those who received sympathetic control with esmolol in terms of maximum change in troponin T release: the median serum troponin T concentration increased from 0.2 ng/ml (interquartile range [IQR] 0.1 to 0.7 ng/ml) to 1.3 ng/ml (IQR: 0.6 to 4.7 ng/ml) in the esmolol group and from 0.3 ng/ml (IQR: 0.1 to 1.2 ng/ml) to 3.2 ng/ml (IQR: 1.5 to 5.3 ng/ml) in the placebo group (p = 0.010). The levels of peak creatine kinase (CK), CK subunit MB (CK-MB), and n-terminal brain natriuretic peptide (NT-proBNP) were lower in the esmolol group compared with placebo (CK 619 U/l [IQR: 250-1,701 U/l] vs. 1,308 U/l [IQR: 610 to 2,324 U/l]; p = 0.013; CKMB 73.5 U/l [IQR: 30 to 192 U/l] vs. 158.5 U/l [IQR: 74 to 281 U/l]; p = 0.005; NT-proBNP: 1,048 pg/ml (IQR: 623 to 2,062 pg/ml] vs. 1,497 pg/ml [IQR: 739 to 3,318 pg/ml]; p = 0.059). Cardiogenic shock occurred in three patients in the placebo group and in none in the esmolol group. CONCLUSIONS Esmolol treatment statistically significantly decreased troponin T, CK, CK-MB and NT-proBNP release as surrogate markers for myocardial injury in patients with STEMI. (Heart Rate Control After Acute Myocardial Infarction; DRKS00000766).
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3.
A phase 2 study of MK-5442, a calcium-sensing receptor antagonist, in postmenopausal women with osteoporosis after long-term use of oral bisphosphonates.
Cosman, F, Gilchrist, N, McClung, M, Foldes, J, de Villiers, T, Santora, A, Leung, A, Samanta, S, Heyden, N, McGinnis, JP, et al
Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA. 2016;(1):377-86
Abstract
UNLABELLED In women with osteoporosis treated with alendronate for >12 months and oral bisphosphonates for >3 of the last 4 years, switching to MK-5442, a calcium receptor antagonist, stimulated endogenous parathyroid hormone (PTH) secretion and increased bone turnover marker levels, but produced a decline in bone mineral density (BMD) at all sites. INTRODUCTION This study assessed the effects of switching from long-term oral bisphosphonate therapy to the calcium-sensing receptor antagonist MK-5442 on BMD and bone turnover markers (BTMs) in post-menopausal women with osteoporosis. METHODS This randomized, active and placebo-controlled, dose-ranging study enrolled 526 postmenopausal women, who had taken alendronate (ALN) for ≥12 months preceding the trial and any oral bisphosphonate for ≥3 of the preceding 4 years and had spine or hip BMD T-scores ≤-2.5 or ≤-1.5 with ≥1 prior fragility fracture. Women were randomized to continue ALN 70 mg weekly or switch to MK-5442 (5, 7.5, 10, or 15 mg daily) or placebo. RESULTS Switching from ALN to MK-5442 produced a dose-dependent parathyroid hormone (PTH) pulse of threefold to sixfold above baseline at 1 h, with PTH levels that remained twofold to threefold above baseline at 4 h and returned to baseline by 24 h. Switching to MK-5442 or placebo increased BTM levels compared to baseline within 3 months and MK-5442 10 mg increased BTM levels compared to placebo by 6 months. With all MK-5442 doses and placebo, spine and hip BMD declined from baseline, and at 12 months, BMD levels were below those who continued ALN (all groups P < 0.05 vs ALN). There was also a dose-dependent increase in the incidence of hypercalcemia with MK-5442. CONCLUSION Switching from ALN to MK-5442 resulted in a pulsatile increase in PTH and increases in BTMs, but a decline in BMD compared with continued ALN. MK-5442 is not a viable option for the treatment of osteoporosis.
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4.
Addition of N-acetyl cysteine to carvedilol decreases the incidence of acute renal injury after cardiac surgery.
Ozaydin, M, Peker, T, Akcay, S, Uysal, BA, Yucel, H, Icli, A, Erdogan, D, Varol, E, Dogan, A, Okutan, H
Clinical cardiology. 2014;(2):108-14
Abstract
BACKGROUND Oxidative stress and inflammation during cardiac surgery may be associated with acute renal injury (ARI). N-acetyl cysteine (NAC) and carvedilol have antioxidant and anti-inflammatory properties. HYPOTHESIS A combination of carvedilol and NAC should decrease the incidence of ARI more than metoprolol or carvedilol. METHODS Patients undergoing cardiac surgery were randomized to metoprolol, carvedilol, or carvedilol plus NAC. End points were occurrence of ARI and change in preoperative to postoperative peak creatinine levels. RESULTS ARI incidence was lower in the carvedilol plus NAC group compared with the metoprolol (21.0% vs 42.1%; P = 0.002) or carvedilol (21.0% vs 38.6%; P = 0.006) groups, but was similar between the metoprolol and carvedilol groups (P = 0.62). Preoperative and postoperative day 1 creatinine levels were similar among the metoprolol (1.02 [0.9-1.2] and 1.2 [0.92-1.45]) the carvedilol (1.0 [0.88-1.08] and 1.2 [0.9-1.5]) and the carvedilol plus NAC groups (1.06 [0.9-1.18] and 1.1 [1.0-1.21] mg/dL; all P values >0.05). Postoperative day 3, day 5, and peak creatinine levels were lower in the carvedilol plus NAC group (1.11 [1.0-1.23], 1.14 [1.0-1.25] and 1.15 [1.0-1.25]) as compared with the metoprolol (1.4 [1.3-1.49], 1.3 [1.0-1.54] and 1.3 [1.0-1.54]) or carvedilol groups (1.2 [1.0-1.52], 1.25 [1.0-1.52] and 1.25 [1.0-1.55] mg/dL; all P values <0.05), but were similar between the metoprolol and carvedilol groups (all P values >0.05). CONCLUSIONS Combined carvedilol and NAC decreased ARI incidence as compared with carvedilol or metoprolol. No difference was detected between carvedilol and metoprolol.
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5.
Protective effect of esmolol on myocardial ischemic injury during open heart surgery in children.
Gui, P, Wu, Q, Wu, J, Yao, S
Paediatric anaesthesia. 2013;(3):217-21
Abstract
OBJECTIVES To investigate the efficacy of esmolol in protecting the myocardium from ischemia during pediatric cardiac surgery. BACKGROUND Esmolol, an ultra-short acting beta 1-adrenoceptor blocker, reduces myocardial injury in adult cardiac operations. However, this technique is rarely used in pediatric cardiac surgery. METHODS Thirty children with ventricular septal defect were randomly allocated to the esmolol group and the control group. Patients received intravenous esmolol (0.05 mg·kg(-1) ·min(-1) after tracheal intubation, 0.3 mg·kg(-1) ·min(-1) during cardiopulmonary bypass (CPB) and 0.03-0.05 mg·kg(-1) ·min(-1) until the end of surgery) or placebo, respectively. RESULTS Plasma levels of creatine kinase-MB, cardiac troponin I in the esmolol group 2 min after completion of CPB, at the end of surgery, 4 h after surgery, and the first postoperative day were significantly lower than those in the control group. Values of heart rate 10 min after induction, 2 min before institution of CPB, 2 min after completion of CPB, and at the end of surgery were significantly lower in the esmolol group; however, mean arterial pressure, CPB time, cross-clamp time, and the rate of heart spontaneous rebeating were not statistically different between two groups. Cumulative postoperative dosage of dopamine in the esmolol group (100.1 ± 53.1 mg) was significantly less than that in the control group (171.4 ± 92.1 mg). CONCLUSIONS Esmolol can protect the myocardium from ischemic injury during CPB in children and significantly reduce the use of inotropic drug.
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6.
Metoprolol vs. carvedilol or carvedilol plus N-acetyl cysteine on post-operative atrial fibrillation: a randomized, double-blind, placebo-controlled study.
Ozaydin, M, Icli, A, Yucel, H, Akcay, S, Peker, O, Erdogan, D, Varol, E, Dogan, A, Okutan, H
European heart journal. 2013;(8):597-604
Abstract
AIMS: Carvedilol and N-acetyl cysteine (NAC) have antioxidant and anti-inflammatory properties. Aim was to evaluate the efficacy of metoprolol, carvedilol, and carvedilol plus NAC on the prevention of post-operative atrial fibrillation (POAF). METHODS AND RESULTS Patients undergoing cardiac surgery (n = 311) were randomized to metoprolol, carvedilol, or carvedilol plus NAC. Baseline characteristics were similar. The incidence of POAF was lower in the carvedilol plus NAC group compared with the metoprolol group (P < 0.0001) or the carvedilol group (P = 0.03). There was a borderline significance for lower POAF rates in the carvedilol group compared with the metoprolol group (P = 0.06). Duration of hospitalization was lower in the carvedilol plus NAC group compared to the metoprolol group (P = 0.004). Multivariate independent predictors of POAF included left-atrial diameter, hypertension, bypass duration, pre-randomization and pre-operative heart rates, carvedilol plus NAC group vs. metoprolol group, and carvedilol plus NAC group vs. carvedilol group. CONCLUSION Carvedilol plus NAC decreased POAF incidence and duration of hospitalization compared with metoprolol and decreased POAF incidence compared with carvedilol.
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7.
Effect of genistein on the activities of cytochrome P450 3A and P-glycoprotein in Chinese healthy participants.
Xiao, CQ, Chen, R, Lin, J, Wang, G, Chen, Y, Tan, ZR, Zhou, HH
Xenobiotica; the fate of foreign compounds in biological systems. 2012;(2):173-8
Abstract
To determine the effect of genistein on cytochrome P450 3A (CYP3A) and P-glycoprotein (P-gp) function using the probe substrates midazolam and talinolol, respectively. Eighteen healthy adult male participants were enrolled in a two-phase randomized crossover design. In each phase, the participants received placebo or genistein for 14 days. On the 15th day, midazolam and talinolol were administered and blood samples were obtained. Midazolam and talinolol pharmacokinetic parameter values were calculated and compared before and after genistein administration. Co-administration of genistein decreased the area under the concentration-time curve from 0 to 36 h (AUC 0-36) (143.65 ± 55.40 ng h/mL versus 126.10 ± 40.14 ng h/mL, p < 0.05), and the area under the concentration-time curve from zero to infinity (AUC 0-∞) (209.18 ± 56.61 ng h/mL versus 180.59 ± 43.03 ng h/mL, p < 0.05), and also maximum concentration (Cmax) of midazolam (48.86 ± 20.21 ng/mL versus 36.25 ± 14.35 ng/mL p < 0.05). Similarly, AUC 0-36 (2490.282 ± 668.79 ng h/mL versus 2114.46 ± 861.11 ng h/mL, p < 0.05), AUC 0-∞ (2980.45 ± 921.09 ng h/mL versus 2626.92 ± 1003.78 ng h/mL, p < 0.05) and Cmax of talinolol (326.58 ± 197.67 ng/mL versus 293.42 ± 127.19 ng/mL, p < 0.05) were reduced by genistein co-administration. The oral clearance of midazolam (1.68 ± 0.85 h-1 versus 3.98 ± 0.59 h-1, p < 0.05) and talinolol (3.34 ± 1.24 h-1 versus 3.79 ± 1.55 h-1, p<0.05) were increased by genistien significantly. Administration of genistein can result in a modest induction of CYP3A and possibly P-gp activity in healthy volunteers.
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8.
The impact of carvedilol and metoprolol on serum lipid concentrations and symptoms in patients with hyperthyroidism.
Ozbilen, S, Eren, MA, Turan, MN, Sabuncu, T
Endocrine research. 2012;(3):117-23
Abstract
BACKGROUND Hyperthyroidism is associated with unpleasant symptoms and hypertension due to increased adrenergic tone. Therefore, beta-blockers are often used in hyperthyroid patients. While some beta-blockers (such as propronolol and metoprolol) may have unwanted effects on lipid profile, carvedilol, a new alpha- and beta-blocker, has been suggested to have some metabolic advantages with respect to lipid profiles in hypertensive patients. However, this has not been shown in hyperthyroid patients. OBJECTIVE We aimed to compare the effects of two beta-blockers (metoprolol and carvedilol) on the lipid profiles of hyperthyroid patients with hypertension. METHODS Thirty patients with hyperthyroidism and hypertension were randomly assigned to receive either carvedilol (n = 15) or metoprolol (n = 15). Thyroid-stimulating hormone (TSH), free T3, free T4, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglyceride, and total cholesterol levels were measured before and following 3 months of treatment. RESULTS Systolic and diastolic blood pressure, heart rate, TSH, and free T4 improved significantly in both treatment groups. There were no statistically significant changes in the lipid parameters in either of the two treatment groups; however, triglyceride levels slightly decreased with carvedilol treatment. There were also no differences between the two groups in terms of the typical symptoms of hyperthyroidism. CONCLUSION Carvedilol might be a preferred agent to treat hyperthyroid patients who have hypertension and dyslipidemia. This is likely due to the possible beneficial effect of carvedilol on lipid parameters, especially on triglyceride levels.
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9.
Effects of preoperative oral beta blocker versus intraoperative nitroprusside or esmolol on quality of surgical field during tympanoplasty.
Amr, YM, Amin, SM
Journal of clinical anesthesia. 2011;(7):544-8
Abstract
STUDY OBJECTIVE To determine whether orally administered atenolol provides an optimal surgical field in comparison to intravenous sodium nitroprusside or esmolol during tympanoplasty. DESIGN Randomized, double-blinded study. SETTING Operating room in a university hospital. PATIENTS 105 ASA physical status 1 and 2 adult patients undergoing tympanoplasty. INTERVENTIONS Patients were randomized to three groups to receive either oral atenolol 50 mg twice daily for one day prior to surgery (Group I), intraoperative nitroprusside infusion (Group II), or intraoperative esmolol infusion (Group III). MEASUREMENTS Quality of the operative field, mean arterial pressure, and heart rate were assessed. Blood gases, liver enzymes, cardiac troponin I, creatine kinase isoenzyme-MB release, blood urea nitrogen, and creatinine concentrations also were measured. MAIN RESULTS Time to achieve target surgical field was significantly reduced in the atenolol group versus the other groups (8.3 ± 3.2, 28.2 ± 6.4, and 17.2 ± 5.3 min, respectively). Heart rate significantly decreased in the atenolol and esmolol groups versus the nitroprusside group (P < 0.0001). Mean arterial pressure after extubation and frequency of rebound hypertension were comparable in the groups. No significant changes in cardiac enzymes, renal and hepatic function, or acid-base status were noted. CONCLUSIONS Although the three drugs are acceptable for obtaining an optimum surgical field, preoperative oral beta blocker appeared to be rapid in onset and was simpler to implement.
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10.
Comparison of carvedilol and metoprolol on serum lipid concentration in diabetic hypertensive patients.
Bell, DS, Bakris, GL, McGill, JB
Diabetes, obesity & metabolism. 2009;(3):234-8
Abstract
CONTEXT Vasoconstricting beta-blocker use is associated with a reduction in HDL cholesterol, higher triglyceride, total cholesterol and LDL cholesterol levels, whereas carvedilol, a vasodilating beta-blocker, has not been associated with these effects. OBJECTIVE To compare in a randomized, double-blind study, the effects of the beta 1-blocker metoprolol tartrate with the combined alpha 1, beta-blocker carvedilol on serum lipid concentrations. METHODS A prospective randomized, double-blind, parallel-group trial compared the effects of carvedilol and metoprolol on total cholesterol, triglycerides, calculated LDL, HDL and non-HDL cholesterol levels at baseline and after 5 months of therapy as a secondary objective in the Glycemic Effects in Diabetes Mellitus: Carvedilol-Metoprolol Comparison in Hypertensive (GEMINI) study. In this study, 1235 participants with type 2 diabetes and hypertension who were receiving renin-angiotensin system blockers were randomized either to carvedilol, receiving 6.25-25 mg twice daily, or to metoprolol tartrate, receiving 50-200 mg twice daily. If needed, hydrochlorothiazide and a dihydropyridine calcium channel blocker were added to achieve blood pressure goals. RESULTS In the metoprolol tartrate group, triglycerides and non-HDL cholesterol increased and both the LDL and the HDL cholesterol levels decreased. In the carvedilol group, total LDL and HDL cholesterol decreased, non-HDL cholesterol was unchanged and triglycerides increased. Comparing the carvedilol and metoprolol tartrate groups, there was no statistically significant difference in LDL and HDL cholesterol levels, but there was a significantly greater decreases with carvedilol in total cholesterol [-2.9%, 95% confidence interval (CI) -4.60 to -1.15, p < 0.001], triglycerides (-9.8%, 95% CI -13.7, -5.75%, p < 0.001) and non-HDL cholesterol (-4.03%, 95% CI -6.3 to -1.8, p < 0.0006). At the end of the study, significantly more participants in the metoprolol tartrate group had had initiation of statin therapy or the statin dose increased than those in the carvedilol group (11 vs. 32%, p = 0.04). CONCLUSIONS In patients with type 2 diabetes currently receiving a renin-angiotensin blocker, compared with metoprolol tartrate, the addition of carvedilol for blood pressure control resulted in a significant decrease in triglyceride, total cholesterol and non-HDL cholesterol levels. The use of metoprolol resulted in a significantly greater rate of initiation of statin therapy or an increase in the dose of existing statin therapy when compared with carvedilol utilization.