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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.
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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3.
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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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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How coenzyme B12-dependent ethanolamine ammonia-lyase deals with both enantiomers of 2-amino-1-propanol as substrates: structure-based rationalization.
Shibata, N, Higuchi, Y, Toraya, T
Biochemistry. 2011;(4):591-8
Abstract
Coenzyme B(12)-dependent ethanolamine ammonia-lyase acts on both enantiomers of the substrate 2-amino-1-propanol [Diziol, P., et al. (1980) Eur. J. Biochem. 106, 211-224]. To rationalize this apparent lack of stereospecificity and the enantiomer-specific stereochemical courses of the deamination, we analyzed the X-ray structures of enantiomer-bound forms of the enzyme-cyanocobalamin complex. The lower affinity for the (R)-enantiomer may be due to the conformational change of the Valα326 side chain of the enzyme. In a manner consistent with the reported experimental results, we can predict that the pro-S hydrogen atom on C1 is abstracted by the adenosyl radical from both enantiomeric substrates, because it is the nearest one in both enantiomer-bound forms. We also predicted that the NH(2) group migrates from C2 to C1 by a suprafacial shift, with inversion of configuration at C1 for both enantiomeric substrates, although the absolute configuration of the 1-amino-1-propanol intermediate is not yet known. Reported labeling experiments demonstrate that (R)-2-amino-1-propanol is deaminated by the enzyme with inversion of configuration at C2, whereas the (S)-enantiomer is deaminated with retention. By taking these results into consideration, we can predict the rotameric radical intermediate from the (S)-enantiomer undergoes flipping to the rotamer from the (R)-enantiomer before the hydrogen back-abstraction. This suggests the preference of the enzyme active site for the rotamer from the (R)-enantiomer in equilibration. This preference might be explained in terms of the steric repulsion of the (S)-enantiomer-derived product radical at C3 with the Pheα329 and Leuα402 residues.
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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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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.
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Nifedipine versus carvedilol in the treatment of de novo arterial hypertension after liver transplantation: results of a controlled clinical trial.
Galioto, A, Semplicini, A, Zanus, G, Fasolato, S, Sticca, A, Boccagni, P, Frigo, AC, Cillo, U, Gatta, A, Angeli, P
Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society. 2008;(7):1020-8
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Abstract
The aim of this study was to compare nifedipine and carvedilol in the treatment of de novo arterial hypertension after orthotopic liver transplantation (OLT). The study included 50 patients who developed arterial hypertension after OLT. Twenty-five patients received nifedipine (group A), and 25 received carvedilol (group B). Patients were defined as intolerant to nifedipine or carvedilol if severe adverse effects developed. These patients stopped the first drug and were switched to the other one. Patients were defined as full responders to monotherapy if there was normalization of blood pressure, and they were defined as partial responders by the need to add a second antihypertensive drug, ramipril. The 2 groups of patients were similar for baseline conditions. At the end of the study, patients intolerant to monotherapy were 48% of group A and 12.5% of group B (P < 0.01). Full responders were 20% of group A and 33.33% of group B (P < 0.01). Partial responders were 22% of group A and 54.1% of group B (P < 0.01). The addition of ramipril normalized blood pressure in 19% of partial responders to monotherapy (75% in partial responders to nifedipine and 30% in partial responders to carvedilol, P < 0.01). In responders to either monotherapy or combined therapy, there was a significant improvement of renal function. In responders to carvedilol, but not in responders to nifedipine, the daily dose of tacrolimus at 1 year should be reduced to 50% compared to the baseline dose to maintain the blood trough level in the therapeutic range.
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Effects of carvedilol versus metoprolol on endothelial function and oxidative stress in patients with type 2 diabetes mellitus.
Bank, AJ, Kelly, AS, Thelen, AM, Kaiser, DR, Gonzalez-Campoy, JM
American journal of hypertension. 2007;(7):777-83
Abstract
BACKGROUND Data suggest that carvedilol possesses antioxidant properties that might provide vascular protection. We sought to compare the effects of carvedilol and metoprolol tartrate on endothelial function and oxidative stress in a head-to-head trial. METHODS Thirty-four patients with type 2 diabetes mellitus (T2DM) and hypertension were randomized to receive either carvedilol (n = 16) or metoprolol (n = 18) in addition to their current antihypertensive medications for 5 months. The following variables were measured pre- and posttreatment: blood pressure, fasting glucose and insulin, insulin resistance by homeostasis-model assessment, hemoglobin A1c, lipids, C-reactive protein (CRP), 8-isoprostane, asymmetric dimethylarginine, oxidized LDL cholesterol, ultrasound assessment of brachial-artery flow-mediated dilation (FMD), nitroglycerin-induced endothelium-independent dilation (EID), brachial and carotid artery distension, distensibility and compliance, and carotid artery intima-media thickness (cIMT). RESULTS Both carvedilol and metoprolol treatment resulted in significant and similar decreases in systolic (P < .05) and diastolic (P < .0001) blood pressure. Compared with metoprolol, carvedilol significantly improved FMD (P < .001). No differences between groups were noted for any of the glycemic or lipid variables except for HDL cholesterol, which significantly decreased (P < .05) in the metoprolol group compared with the carvedilol group. No differences were observed between groups for CRP, the markers of oxidative stress, EID, arterial stiffness, or cIMT. CONCLUSIONS Compared with metoprolol, carvedilol significantly improves endothelial function in patients with T2DM. Changes in glycemic control and oxidative stress do not seem to explain the observed improvements in FMD, which suggests that other mechanisms may be involved.
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The antioxidative effects of long-term treatment are more pronounced for carvedilol than for atenolol in post-myocardial infarction patients.
Jonsson, G, Abdelnoor, M, Seljeflot, I, Arnesen, H, Hostmark, AT, Kjeldsen, SE, Os, I, Westheim, AS
Journal of cardiovascular pharmacology. 2007;(1):27-32
Abstract
Oxidative stress might exert deleterious cardiovascular effects. The aim of the present study was to compare the antioxidative effects of carvedilol and atenolol. Levels of oxidized low-density lipoprotein cholesterol (ox-LDL), vitamin E, and thiobarbituric acid reactive substances (TBARS) were measured. In a prospective, open, and end-point-blinded study, 232 patients with an acute myocardial infarction (AMI) were randomized to receive either carvedilol or atenolol at equipotent doses, and the previously mentioned 3 parameters were measured at baseline and after 12 months of active treatment, with changes during the study period being compared both within and between the groups. Ox-LDL decreased in both treatment modalities, from 40.5 +/- 15.6 to 35.0 +/- 13.8 U/L, P = 0.0001, in the carvedilol group and from 40.3 +/- 16.5 to 37.4 +/- 13.1 U/L, P = 0.044, in the atenolol group, with a significant between-group difference in the changes (P = 0.036). The levels of vitamin E did not change during carvedilol treatment (31.0 +/- 10.2 vs 31.7 +/- 11.1 micromol/L), but it decreased marginally in the atenolol group (30.8 +/- 12.1 vs 27.2 +/- 9.1 micromol/L, P = 0.056), with a significant between-group difference (P = 0.008). No significant change in TBARS was observed between the carvedilol and atenolol groups (P = 0.454). These results indicate that carvedilol has a more pronounced antioxidative effect than atenolol in post-AMI patients, which might be of clinical importance.