Carvedilol Group Research Articles

Combination of carvedilol with variceal band ligation in prevention of first variceal bleed in Child-Turcotte-Pugh B and C cirrhosis with high-risk oesophageal varices: the ‘CAVARLY TRIAL’

ObjectivesBeta-blockers and endoscopic variceal band ligation (VBL) have been preferred therapies for primary prophylaxis of variceal bleeding. However, the choice of therapy in patients with advanced liver disease with high-risk...

Carvedilol ameliorates experimental atherosclerosis by inhibiting the NLRP3 inflammasome.

To investigate the protective effect of carvedilol against atherosclerosis by inhibiting the NLRP3 inflammasome. In-vitro experiments, human umbilical vein endothelial cells (HUVEC) were divided into the control group, ox-LDL group, carvedilol 5 μM group, carvedilol 10 μM group, and carvedilol 20 μM group. The optimal concentration of carvedilol was determined using the CCK-8 method to assess cell proliferation levels and oil red O staining to observe intracellular lipid droplet formation. Subsequently, the cells were further divided into the control group, ox-LDL group, carvedilol 5 μM (optimal concentration) group, and MCC950 (inhibitor of NLRP3 Inflammasome) group. The expression levels of intracellular proteins NLRP3, pro-Caspase-1, Caspase1, pro-IL-1β, IL-1β, p65, GSDMD, and N-GSDMD were detected by ELISA, or Western Blotting. Compared to the control group, the ox-LDL group exhibited a significant reduction in cell proliferation level (P<0.05), accompanied by an increase in lipid droplet formation upon induction. In contrast, pretreatment with carvedilol at concentrations of 5 μM, 10 μM, and 20 μM effectively promoted cell proliferation (P<0.05) and inhibited intracellular lipid droplet formation. Notably, the most pronounced effect was observed with carvedilol pretreatment at a concentration of 5μM. Furthermore, compared to the control group, HUVEC cells in the ox-LDL group demonstrated substantial upregulation of NLRP3, pro-Caspase-1, Caspase1, pro-IL-1β, IL-1β, p65 GSDMD and N-GSDMD; however, these markers were downregulated following treatment with carvedilol and MCC950 administration-particularly evident in the carvedilol group. Carvedilol effectively inhibits the progression of atherosclerosis by targeting the NLRP3 inflammasome, thereby providing valuable mechanistic insights into its beneficial effects on atherosclerotic cardiovascular disease.

Early initiation of oral beta-blocker improves long-term survival in patients with acute myocardial infarction who underwent primary percutaneous coronary intervention

BackgroundThe optimal timing for the initiation of oral beta-blockers after acute myocardial infarction (MI) remains unclear within the context of current primary percutaneous coronary intervention (PCI) practice.MethodsThis retrospective cohort study included 412 consecutive patients admitted with a diagnosis of acute MI between January 2007 and August 2016 who underwent successful primary PCI and were given oral carvedilol during hospitalization. Early and late carvedilol groups were based on initiation within the first 24 h or after. Propensity score matching (1:1) incorporating 21 baseline characteristics yielded 47 matched pairs. Timing of carvedilol initiation was evaluated in relation to patient outcomes including time to all-cause mortality, using Kaplan-Meier estimates on the matched cohort and additional confirmation in multivariable regression analysis among the entire cohort.ResultsMedian follow-up period was 828 days. All-cause death occurred in 14 patients (4.7%) and 18 patients (15.8%) of the early and late carvedilol groups. After propensity score matching, initiation of oral carvedilol within the first 24 h was associated with lower all-cause mortality (6.4% vs. 25.5%, hazard ratio 0.28, 95% confidence interval 0.06 − 0.89, p = 0.036), as well as lower in-hospital mortality (0 vs. 14.9%, p = 0.018).ConclusionsThese results provide evidence that initiation of oral carvedilol within the first 24 h reduces the risk of long-term mortality, in acute MI patients who underwent primary PCI, supporting current guidelines recommendation.

Abstract 20: Orthostatic Hypotension in Patients with Heart Failure taking Carvedilol or Metoprolol

Background: Metoprolol succinate and carvedilol are widely prescribed beta-blockers for the treatment of heart failure (HF). Both can reduce mortality, but unlike the β-1 selective metoprolol, carvedilol has α-1 blocking effects. Since orthostatic hypotension (OH) is a common comorbidity in HF patients, we conducted a case-control study to assess if the vasodilatory effect of carvedilol, compared to metoprolol, is associated with a higher risk for newly diagnosed OH. Methods: A deidentified retrospective database of all HF patients seen at the Vanderbilt University Medical Center who were taking metoprolol or carvedilol (n=272,019) was used. Cases of newly diagnosed OH were defined as those who had a new diagnosis of OH after the first mention of either drug (n=3,006) and controls as those who did not have a diagnosis of OH (n=269,013). Demographic information, presence of other comorbidities, and concomitant use of other drugs known to cause hypotension were obtained. One-way analysis of variance (ANOVA) and Pearson’s chi-square tests were used to compare continuous and categorical variables between both groups, respectively. Results: OH was diagnosed in 1% of all patients and metoprolol was more commonly prescribed than carvedilol (81% vs. 19%). Compared to controls, OH patients were older (58 vs. 66 yr) and had a higher rate of hypertension (22% vs. 96%), Parkinson disease (1% vs. 3%) and concomitant use of diuretics, calcium channel blockers, other α-1 blockers and other drugs associated with OH (Table). The prevalence of OH cases was higher in the carvedilol group compared to the metoprolol group (1.96% vs. 0.91%), but only age differed between the OH cases in both groups (metoprolol: 64 vs. carvedilol: 71 yr). We found that patients were more likely to be diagnosed with OH after taking carvedilol vs. metoprolol (unadjusted odds ratio 2.2078, 95% CI 2.0448 – 2.3838, p &lt; 0.001). Conclusions: The prevalence of OH among patients with heart failure was higher in patients taking carvedilol compared to metoprolol. Given that both drugs have similar beneficial effects on mortality, metoprolol appears to be preferable in the treatment of heart failure in patients at risk of developing OH. Studies to further assess the relationship between heart failure classification and orthostatic hypotension are needed.

Cardioprotective Diet to Prevent Anthracycline-Induced Cardiotoxicity in Patients with Breast Cancer: A Randomized Open-Label Controlled Trial.

Objectives: Several studies have indicated that dietary interventions may offer protection against the development of cardiac damage in the case of anthracycline-induced cardiomyopathy (AIC). The goal of this study was to assess whether an evidence-based cardioprotective diet can be effective in preventing AIC in patients with breast cancer. Design: Randomized, open-label, controlled trial. The study period was set for 18 weeks, and the data were analyzed by generalized estimating equation modeling and one-way repeated measures analysis of variance. Setting/Location: Shahid Rajaie Hospital affiliated (Tehran, Iran). Subjects: Fifty anthracycline-treated patients with breast cancer. Interventions: Patients were randomized to receive either a 2-hour training in evidence-based cardio-protective diet or Carvedilol 6.25 mg bid. Outcome Measures: The primary outcome was the number of patients with abnormal left ventricular ejection fraction (LVEF) after 18 weeks. Results: At week 18, 12 (48%) out of 25 participants in the cardioprotective diet group had abnormal LVEF in comparison with 21 (84%) out of 25 in the carvedilol group (p = 0.007). Also, 2 (8%) out of 25 in the cardioprotective diet group compared with 7 (28%) out of 25 participants in the carvedilol group had abnormal global longitudinal strain (p = 0.066). The diet group showed significant improvements in the quality-of-life dimensions named "health change" and "general health" compared with the carvedilol group using the Short Form-36 Health Survey questionnaire. Conclusions: This study suggests that an evidence-based cardioprotective diet can contribute to the prevention of AIC. Although current treatments for AIC can be effective, further research is mandatory for more options.

Effect of carvedilol versus placebo on cardiac function in anthracycline-exposed survivors of childhood cancer (PREVENT-HF): a randomised, controlled, phase 2b trial

Carvedilol improves cardiac function in patients with heart failure but remains untested as cardioprotective therapy in long-term childhood cancer survivors (ie, those who have completed treatment for childhood cancer and are in remission) at risk for heart failure due to high-dose anthracycline exposure. We aimed to evaluate the activity and safety of low-dose carvedilol for heart failure risk reduction in childhood cancer survivors at highest risk for heart failure. PREVENT-HF was a randomised, double-blind, phase 2b trial done at 30 hospitals in the USA and Canada. Patients were eligible if they had any cancer diagnosis that resulted in at least 250 mg/m2 cumulative exposure to anthracycline by age 21 years; completed their cancer treatment at least 2 years previously; an ejection fraction of at least 50% or fractional shortening of at least 25%, or both; and bodyweight of at least 40 kg. Patients were randomly assigned (1:1) with automated computer-generated permuted block randomisation (block size of 4), stratified by age at diagnosis, time since diagnosis, and history of chest-directed radiotherapy, to carvedilol (up-titrated from 3·125 g per day to 12·5 mg per day) or placebo orally for 2 years. Participants, staff, and investigators were masked to study group allocation. The primary endpoint was to establish the effect of carvedilol on standardised left ventricular wall thickness-dimension ratio Z score (LVWT/Dz). Treatment effects were analysed with a linear mixed-effects model for normally distributed data with a linear time effect and testing the significance of treatment*time interaction in the modified intention-to-treat (mITT) cohort (ie, all randomly assigned participants who had a baseline and at least one subsequent echocardiogram measurement). Safety was assessed in the ITT population (ie, all randomly assigned participants). This trial was registered with ClinicalTrials.gov, NCT027175073, and enrolment and follow-up are complete. Between July 3, 2012, and June 22, 2020, 196 participants were enrolled, of whom 182 (93%) were eligible and randomly assigned to either carvedilol (n=89) or placebo (n=93; ITT population). Median age was 24·7 years (IQR 19·6-36·6), 91 (50%) participants were female, 91 (50%) were male, and 119 (65%) were non-Hispanic White. As of data cutoff (June 10, 2022), median follow-up was 725 days (IQR 378-730). 151 (n=75 in the carvedilol group and n=76 in the placebo group) of 182 participants were included in the mITT population, among whom LVWT/Dz was similar between the two groups (-0·14 [95% CI -0·43 to 0·16] in the carvedilol group vs -0·45 [-0·77 to -0·13] in the placebo group; difference 0·31 [95% CI -0·10 to 0·73]; p=0·14). Two (2%) of 89 patients in the carvedilol group two adverse events of grade 2 or higher (n=1 shortness of breath and n=1 arthralgia) and none in the placebo group. There were no adverse events of grade 3 or higher and no deaths. Low-dose carvedilol appears to be safe in long-term childhood cancer survivors at risk for heart failure, but did not result in significant improvement of LVWT/Dz compared with placebo. These results do not support the use of carvedilol for secondary heart failure prevention in anthracycline-exposed childhood cancer survivors. National Cancer Institute, Leukemia & Lymphoma Society, St Baldrick's Foundation, Altschul Foundation, Rally Foundation, American Lebanese Syrian Associated Charities.

Carvedilol alleviates the detrimental effects of azathioprine on hepatic tissues in experimental rats: Focusing on redox system, inflammatory and apoptosis pathways.

Drug-induced liver injury is becoming an increasingly important topic in drug research and clinical practice. Due to a lack of experimental animal models, predicting drug-induced liver injury in humans is challenging. Azathioprine (AZA) is a classical immunosuppressant with hepatotoxic adverse effects. The present study aimed to address the hepatoprotective effect of carvedilol (CAR) against AZA-induced hepatocellular injury via assessing redox-sensitive signals. To achieve this purpose, rats were allocated into four groups: control, CAR only, AZA only, and CAR plus AZA groups. The induction of hepatic injury was induced by a single intraperitoneal injection of AZA at a dose of 50mg/kg on the 6th day of the experiment. Each experimental protocol was approved and supervised by the Ethics Committee for Animal Experiments. The results of the present study revealed that CAR administration significantly diminished AZA-induced hepatic dysfunction, as evidenced by relief of hepatic function biomarkers and histopathological aberration induced by AZA injection. Besides, CAR restored oxidant/antioxidant balance as well as NRF2 expression. In addition, CAR suppressed inflammatory response induced by AZA challenge as evidenced by downregulation of TLR4, TNF-α, MPO, and eNOS/iNOS levels in hepatic tissue. Moreover, CAR recovered apoptotic/anti-apoptotic status by modulation of caspase-3/Bcl2 expression. Taken together, CAR protects against AZA-induced hepatic injury via antioxidant, anti-inflammatory, and anti-apoptotic activities. These findings revealed that CAR could be a good candidate for hepatic injury protection and can be added to AZA therapeutic regimen to reduce their adverse effect.

Effects of the beta-blocker carvedilol on arrhythmia and long-term clinical outcomes in benign prostate hypertrophy patients.

Benign prostatic hypertrophy (BPH) is associated with autonomic dysfunction and sympathetic nervous system mediated by the alpha receptor. However, limited data exist regarding the effects of the beta-blocker (BB) carvedilol on arrhythmia and urologic outcomes in BPH patients. Our database of patients diagnosed with BPH from 2015 to 2020 was used to obtain echocardiography and electrocardiogram data. Inclusion criteria were BPH patients taking BBs. International Prostate Symptom Score questionnaire were used to evaluate the urinary symptoms and quality of life. Among 448 patients with BPH (69.2 ± 10.9 years) taking BBs, 219 patients took carvedilol (48.9%) and 229 patients took a non-carvedilol BB (51.1%; bisoprolol, 184 patients, 80% or nebivolol, 45 patients, 20%). Difference in the baseline characteristics was not observed. During the median 36-month follow-up, a lower incidence of arrhythmic events (P = .029), total urologic events (P < .001), and less use of additive alpha-blocker was observed in the carvedilol group (P = .022). In multivariate analysis, less carvedilol use (P = .019), heart failure (P < .001), stroke (P < .001), and cardiomyopathy (P = .046) were independent risk factors for arrhythmic events. In addition, less carvedilol use (P = .009) and older age (P = .005) were independent risk factors for urologic events based on BB type at the median 36-month follow-up. The use of carvedilol was associated with less arrhythmic events in BPH patients with palpitation and decreased the incidence of urologic events in BPH compared with the use of non-carvedilol BBs in long-term follow-up.

Comparative effects of nebivolol and carvedilol on left ventricular diastolic function in older patients with heart failure and preserved ejection fraction

BackgroundAlthough many studies have compared carvedilol and nebivolol in heart failure (HF) patients with reduced left ventricular ejection fraction (LVEF), such comparative studies for the elderly have not been reported yet. Nebivolol is known to be effective for improving diastolic function of elderly patients with HF. Thus, this study aimed to determine whether nebivolol could improve LV diastolic function to a greater extent than carvedilol in older patients aged over 70 years. MethodsThis trial was a prospective, randomized, open-label, single-center, active-controlled study that enrolled 62 patients with class II or III HF over 70 years of age with an LVEF ≥40%. Patients were randomized into a carvedilol group or a nebivolol group. Transthoracic echocardiography was performed at baseline and 12 months by the same investigator who was blinded to clinical data. The primary endpoint was E/e′ measured by echocardiographic evaluation 12 months after treatment. ResultsThe median duration of follow-up was 24 months. Baseline clinical characteristics and echocardiographic parameters, such as LV diastolic function indices, did not differ significantly between carvedilol and nebivolol groups. Twelve-month follow-up echocardiography data showed no significant difference in E/e′ or other LV diastolic function indices between the two groups. There were no significant changes in echocardiographic parameters over 12 months in either group. ConclusionsThere was no difference between carvedilol and nebivolol for improving diastolic function of elderly HF patients with LVEF ≥40%. This study showed no superiority of nebivolol over carvedilol in elderly patients with HF.

Comparison of the Use of Carvedilol Versus Nebivolol in the Treatment of Acute Decompensation in the Patient with Chronic Heart Failure: Evaluation of Clinical Variables

Previous trials demonstrated the safety of using beta-blockers in the acute decompensation of heart failure; it is unknown whether the use of nebivolol translates into an improvement in clinical parameters at 96 hours, compared to the use of carvedilol in a similar study group. Objectives: To compare the effect of 2 treatment strategies, where the difference is made by the type of beta-blocker, in patients with acutely decompensated chronic heart failure. Methods: A single-center, prospective, experimental, randomized, double-blind clinical trial was carried out, 22 patients with LVEF ≤ 40% were randomly assigned to receive carvedilol or nebivolol with daily dose increase, clinical variables were measured for 96 hours. Results: The carvedilol group reached a maximum dose of 33.3 ± 10 mg and nebivolol 9.37 ± 1.25 mg, with both treatment strategies compensation was achieved in more than 50% of the patients in both groups, without statistically significant differences for the majority of patients. clinical variables, except for greater weight loss in the carvedilol group, reaching an absolute reduction of 5.62 kg (95% CI 3.22-8.02 kg) versus nebivolol with 2.54 kg (95% CI 0. 14-4.94 kg) at 96 hours of follow-up (p 0.001) Conclusions: In patients with acutely decompensated chronic heart failure and reduced LVEF, the use of beta-blockers is safe and well tolerated, guarantees clinical improvement and rapid compensation, with doses diuretic drops. The group with carvedilol showed greater weight reduction, compared to the nebivolol group in the study population.

Carvidelol Vs Propanol for Secondary Prophylaxis of Variceal Hemorrhage in Liver Cirrhosis Patients

Propranolol and Carvedilol are the currently used medications for main prophylaxis of variceal bleeding. Objective: To investigate the efficacy of carvedilol vs propranolol for prevention of variceal hemorrhage in liver cirrhosis patients. Methods: This prospective comparative study was carried out on 196 cirrhotic patients in the Gastroenterology Department of Lady Reading Hospital, Peshawar in collaboration with Pharmacology department of Khyber Medical University, Peshawar from July 2018 to June 2020. Patients with no prior history of primary variceal prophylaxis treatment and variceal bleeding were enrolled. All the patients were categorized into two groups: Group-I (Carvedilol) and Group-II (propanol). Frank hematemesis, melena, and endoscopic assessment was used for the evaluation of variceal bleeding. Results: Of the total 196 liver cirrhosis patients, Group-I and Group-II had 102 (52%) and 94 (48%) respectively. Ultrasonography found splenomegaly in 88% of cases and moderate to severe ascites in 42.6% of the patients investigated. The success rate of carvedilol and propanol group was 76% and 64.8% respectively. The side-effects and complication rate were significantly lower in Group-I than Group-II. The prevalence of variceal bleeding was 16.7% (n=17) and 11.7% (n=11) respectively. Conclusions: Carvedilol is an excellent treatment alternative for prevention of variceal bleeding than propranolol in terms of side-effects and complications rate.

Comparing the Efficacy of Carvedilol and Flecainide on the Treatment of Idiopathic Premature Ventricular Complexes from Ventricular Outflow Tract: A Multicenter, Randomized, Open-Label Pilot Study.

The mechanism of premature ventricular complexes (PVC) occurring in the ventricular outflow tract (OT) is related to an intracellular calcium overload and delayed afterdepolarizations that lead to triggered activity. The guidelines recommend using beta-blockers and flecainide for idiopathic PVCs, but they also acknowledge the limited evidence supporting this recommendation. We conducted a multicenter, randomized, open-label pilot study comparing the effect of carvedilol and flecainide on OT PVC, which are widely used to treat this arrhythmia. Patients with a 24 h Holter recording a PVC burden ≥ 5%, which showed positive R waves in leads II, III, and aVF, and without structural heart disease were enrolled. They were randomly assigned to the carvedilol or flecainide group, and the maximum tolerated dose was administered for 12 weeks. A total of 103 participants completed the protocol: 51 with carvedilol and 52 with flecainide. After 12 weeks of treatment, the mean PVC burden significantly decreased in both groups: 20.3 ± 11.5 to 14.6 ± 10.8% with carvedilol (p < 0.0001) and 17.1 ± 9.9 to 6.6 ± 9.9% with flecainide (p < 0.0001). Both carvedilol and flecainide effectively suppressed OT PVCs in patients without structural heart disease, with flecainide showing a superior efficacy compared to carvedilol.

Abstract 5250: Effect of the β-blocker carvedilol in preventing DMBA-induced mammary gland tumor growth

Abstract According to global cancer statistics, breast cancer has now become the most diagnosed cancer and has become the fifth leading cause of cancer-related deaths worldwide. A promising method of retarding cancer-related mortality is cancer chemoprevention. However, there is no drug available that can be used routinely as a breast cancer-preventative agent. As carvedilol (CAR), an FDA-approved beta-adrenergic receptor blocker, reduces breast cancer mortality, we hypothesized that CAR might act as a breast cancer preventative agent. Three protocols were utilized to evaluate the ability of CAR to prevent 7,12-Dimethylbenz(a)anthracene (DMBA)-induced mammary tumors in rats. In protocol 1, two doses of CAR (2 and 10 mg/kg) were administered in drinking water as a 7-day pretreatment and throughout the study. In protocol 2, 10 mg/kg tamoxifen and 10 mg/kg carvedilol were provided as a 7-day pretreatment, and treatment was halted after six weeks. In protocol 3, CAR and the non-β-blocking enantiomer R-carvedilol (10 mg/kg) were given as a 7-day pretreatment and throughout the study. In all studies, animals were palpated weekly beginning at week 5 to detect the presence and location of mammary tumors. Tumors were measured using a caliper, and the experiments terminated at week 13. In protocol 1, only 10 mg/kg CAR was effective in delaying DMBA-mediated tumor occurrence (p = 0.0002); the first appearance of tumors and median tumor appearance in CAR-treated rats were separated from rats receiving DMBA alone by 2 and 4 weeks, respectively. However, tumors that did form grew at the same rate in all groups. In protocol 2, tamoxifen served as a control to prevent DMBA-mediated tumors; only one tamoxifen-treated rat developed a tumor at the end of the study. The tamoxifen-treated rats tumor formation was not statistically different than negative controls; however, the CAR group was not statistically different from the DMBA group. In protocol 3, CAR and R-CAR treatment showed delayed tumor formation and growth compared to the DMBA-only group, although not statistically significant. Combining all DMBA and 1-week pretreatment CAR data (n = 58 and 40, respectively), CAR effectively prevents DMBA-induced tumor incidence (p = 0.001), with a 3-week differential in the median tumor formation between the two groups. Therefore, continuous CAR treatment is essential to achieve the observed chemopreventive effects. As carvedilol is a clinically used beta-blocker, the results provide significant implications in breast cancer chemoprevention. Citation Format: Pabitra Kumar Sardar, Steven Yeung, Ayaz Shahid, Bradley T. Andresen, Ying Huang. Effect of the β-blocker carvedilol in preventing DMBA-induced mammary gland tumor growth. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5250.

Influence of carvedilol and thyroid hormones on inflammatory proteins and cardioprotective factor HIF-1α in the infarcted heart

Inflammatory pathways of Toll-like receptor 4 (TLR4) and NLRP3 inflammasome contribute to acute myocardial infarction (AMI) pathophysiology. The hypoxia-inducible factor 1α (HIF-1α), however, is a key transcription factor related to cardioprotection. This study aimed to compare the influence of carvedilol and thyroid hormones (TH) on inflammatory and HIF-1α proteins and on cardiac haemodynamics in the infarcted heart. Male Wistar rats were allocated into five groups: sham-operated group (SHAM), infarcted group (MI), infarcted treated with the carvedilol group (MI+C), infarcted treated with the TH group (MI+TH), and infarcted co-treated with the carvedilol and TH group (MI+C+TH). Haemodynamic analysis was assessed 15 days post-AMI. The left ventricle (LV) was collected for morphometric and Western blot analysis. The MI group presented LV systolic pressure reduction, LV end-diastolic pressure elevation, and contractility index decrease compared to the SHAM group. The MI+C, MI+TH, and MI+C+TH groups did not reveal such alterations compared to the SHAM group. The MI+TH and MI+C+TH groups presented reduced MyD88 and NLRP3 and increased HIF-1α levels. In conclusion, all treatments preserve the cardiac haemodynamic, and only TH, as isolated treatment or in co-treatment with carvedilol, was able to reduce MyD88 and NLRP3 and increase HIF-1α in the infarcted heart.

Effect of Carvedilol Versus Metoprolol on Contrast-Induced Nephropathy in Patients with Acute Coronary Syndrome Undergoing Percutaneous Intervention Therapy.

Carvedilol can inhibit inflammation, vasoconstriction, and oxidative stress, which play important roles in the development and progression of contrast-induced nephropathy (CIN). To the best of our knowledge, no studies have investigated the potential effect of carvedilol on the prevalence of CIN after percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS). The present study aimed to determine whether carvedilol use is associated with the development of CIN. A total of 319 patients (mean age, 59.2 ± 12.4years; 77.7% male) with ACS who underwent urgent PCI at our institution between May 2019 and May 2022 were included prospectively. Overall, 100 and 219 patients were assigned to the carvedilol and metoprolol groups, respectively. The prevalence of CIN was significantly lower in the carvedilol group (6.0%) than in the metoprolol group (18.3%; P = .003). Multivariate analysis revealed that carvedilol use (odds ratio [OR] .250, 95% confidence interval [CI] .092-.677, P = .006), amount of contrast agent (OR 1.004, 95% CI 1.000-1.008, P = .031), and admission estimated glomerular filtration rate (OR .978, 95% CI 0.960-.995, P = .014) were independently associated with the development of CIN. The use of carvedilol may be a promising option for the prevention of CIN in patients with ACS undergoing urgent PCI.

Evaluation of the Effect of Carvedilol in Preventing Right Ventricular Dysfunction in Breast Cancer Patients Receiving Anthracycline.

Today, it has been shown that it is possible for right ventricular (RV) wall motion abnormalities or RV functional disorders to occur during cancer treatment. Now, considering the effect of carvedilol on beta 1, 2, and alpha receptors and its antioxidant properties, it seems that it can prevent RV abnormalities. Therefore, the aim of this study was to investigate the possible protective effects of carvedilol in preventing RV dysfunction in patients with breast cancer treated with anthracyclines. The present single-blind clinical trial study was performed on 23 patients with breast cancer that 12 of them received only the anthracycline antineoplastic doxorubicin (Adriamycin®) chemotherapy (control group) and 11 patients received carvedilol in addition to anthracycline. To evaluate the effect of carvedilol, patients underwent transthoracic echocardiography before intervention and 2 weeks after the end of treatment with anthracyclines. The two parameters of RV ejection fraction and RV fractional area change in the carvedilol group with a mean of 66.41% ± 8.10% and 51.85% ± 6.89% were slightly higher than the control group with a mean of 64.58% ± 6.83% and 50.48 ± 5.79%, respectively, which was not statistically significant (P > 0.05). In contrast, RV S wave tissue Doppler imaging (S-TDI) in the control group with a mean of 0.13 ± 0.02 m/s was significantly lower than the carvedilol group with a mean of 0.14 ± 0.02 m/s (P = 0.022). According to the results of the present study, the effect of using carvedilol as a preservative on improving RV function was seen compared to the control group, although this difference was not statistically significant.

Comparison of The Use of Carvedilol Versus Nebivolol in The Treatment of Acute Decompensation in The Patient With Chronic Heart Failure: Evaluation of Clinical Variables

Previous trials demonstrated the safety of using beta-blockers in the acute decompensation of heart failure; it is unknown whether the use of nebivolol translates into an improvement in clinical parameters at 96 hours, compared to the use of carvedilol in a similar study group. Objectives: To compare the effect of 2 treatment strategies, where the difference is made by the type of beta-blocker, in patients with acutely decompensated chronic heart failure. Methods: A single-center, prospective, experimental, randomized, double-blind clinical trial was carried out, 22 patients with LVEF ≤ 40% were randomly assigned to receive carvedilol or nebivolol with daily dose increase, clinical variables were measured for 96 hours. Results: The carvedilol group reached a maximum dose of 33.3 ± 10 mg and nebivolol 9.37 ± 1.25 mg, with both treatment strategies compensation was achieved in more than 50% of the patients in both groups, without statistically significant differences for the majority of patients. clinical variables, except for greater weight loss in the carvedilol group, reaching an absolute reduction of 5.62 kg (95% CI 3.22-8.02 kg) versus nebivolol with 2.54 kg (95% CI 0. 14-4.94 kg) at 96 hours of follow-up (p 0.001). Conclusions: In patients with acutely decompensated chronic heart failure and reduced LVEF, the use of beta-blockers is safe and well tolerated, guarantees clinical improvement and rapid compensation, with doses diuretic drops. The group with carvedilol showed greater weight reduction, compared to the nebivolol group in the study population.

Effect of P-glycoprotein Inhibitor (Carvedilol) on Developmental Outcome Methotrexate are Given Alone and in Combination of Pregnant Rats

&#x0D; &#x0D; &#x0D; &#x0D; This study was performed according to FDA protocol to evaluate the developmental effects of carvedilol (P-glycoprotein inhibitor), methotrexate (P-glycoprotein substrate) and their combination at therapeutic doses on pregnant rats. Sixty Albino Wistar rats (40 female rats and 20 males) were allocated randomly into four groups orally administered 0.72 mg/kg carvedilol (Cv-treated group [TG]), 0.36 mg/kg methotrexate (MTX-TG), combined doses carvedilol+methotrexate (Cv+MTX-TG), and distilled water (control group) for 2 months in male and 2 weeks in female rats before mating and after copulation, then approval of pregnancy; dosing continued in female groups during pregnancy and lactation periods. Half of the animal groups were euthanized one day before parturition to study prenatal effects, while the other half left for parturition and lactation to study postnatal effect. The results of fertility index recorded in Cv-TG (71.43%), MTX-TG (42.46%) and Cv+MTX-TG (38.47%) was markedly lower than that in control (83.33%) group with lower gestation index was recorded in MTX-TG (80%) and Cv+MTX-TG (60%) than that in Cv-TG (100%) and the control group (100%). The result of resorbed and fetal death recorded a higher percent in Cv-MTX-TG in comparison with MTX-TG and Cv-TG; Cv-MTX-TG fetuses also recorded more anomalies, including hemorrhagic placenta, curved legs, and microcephaly during prenatal period. The postnatal effects showed that the Cv+MTX-TG group recorded a higher decrease in number of pups born, their weight, and increase in number of stillbirths in comparison with methotrexate followed by carvedilol groups in comparison with control group, while the result of viability index recorded (Cv-TG=98.15%, MTX-TG=93.93% and Cv+MTX-TG=76.19%) and lactation index (Cv-TG=77.36%, 83.87% and Cv+MTX-TG=75%). The postnatal anomalies were only recorded in Cv+MTX-TG included skull defect and ulceration, blindness, skin lesion, and alopecia in lactating pups. It is concluded that inhibition of P-gp by carvedilol might increase the placental passage and increase methotrexate concentration in fetal and pups’ tissue with consequence of increase toxic effect of methotrexate both in fetus and pups of Cv+MTX-TG group which might explain the present results of teratogenic study.&#x0D; &#x0D; &#x0D; &#x0D;

Carvedilol exhibits anti-acute T lymphoblastic leukemia effect in vitro and in vivo via inhibiting β-ARs signaling pathway

An increasing number of studies have focus upon β-adrenergic receptor blockers and their anti-tumor effects. However, the use of Carvedilol (CVD), the third generation β-AR blocker, has not been explored for use against T-ALL. In this study, the level of β-ARs was explored in pediatric T-ALL patients. Moreover, the antitumor effects of CVD against T-ALL were assessed in vitro and in vivo, and the underlying mechanisms were investigated. The viability of T-ALL cells following CVD treatment was detected using a CCK-8 assay, and the apoptotic and cell cycle effects were measured using flow cytometry. The protein levels of β-ARs, cAMP, Epac, JAK2, STAT3, p-STAT3, PI3K, p-PI3K, AKT, p-AKT, mTOR, cyclin D1, PCNA, and cleaved caspase-3 were assessed by Western blotting. In vivo experiments were used to investigate the effect of CVD on T-ALL growth in mice. The results indicated that β-ARs were highly expressed in the newly diagnosed T-ALL cells when compared to those in the control group (P < 0.05). In vitro, CVD significantly inhibited T-ALL cell viability, promoted apoptosis and blocked the G0/G1 phase of cell cycle. After CVD treatment, the protein levels of β-ARs, cAMP, Epac, PI3K, p-PI3K, AKT, p-AKT, mTOR, JAK2, STAT3, p-STAT3, cyclin D1 and PCNA were significantly downregulated (P < 0.05); whereas cleaved caspase-3 was significantly upregulated (P < 0.05). In vivo, the volume and weight of the xenograft tumors were significantly decreased in the CVD group (P < 0.05). CVD promoted xenograft tumor apoptosis and reduced the proportion of CEM-C1 cells in murine peripheral blood and bone marrow (P < 0.05). Our results demonstrate that β-ARs are expressed in T-ALL. CVD has a strong antitumor effect against T-ALL and inhibits β-AR associated signaling pathways. Therefore, CVD may provide a potential therapy for T-ALL.

Hepatoprotective effects of carvedilol and crocin against leflunomide-induced liver injury

Leflunomide-induced liver injury has been an important problem since its approval. Although, severe cases of leflunomide-induced liver injury leading to hospitalization are rare, the risk is higher with concurrent liver disease or use of other hepatotoxic drugs.The current study was conducted to investigate the potential protective effects of carvedilol and crocin alone and in combination against leflunomide-induced hepatic injury and to clarify the possible mechanism(s) through which carvedilol and crocin may elicit their effects.Fifty male albino mice were allocated into five groups: normal control group, leflunomide group, carvedilol group, crocin group, and combination group. These groups were given vehicle, leflunomide, leflunomide plus carvedilol, leflunomide plus crocin, and leflunomide plus combination of carvedilol and crocin, respectively. The study was conducted for 8 weeks, and different parameters were assessed.The results demonstrated that leflunomide significantly increased the serum levels of AST, ALT, ALP, hepatic MDA, nitrite, mTOR gene, PI3K gene, TGF-β, and the pathological changes alongside with the significant decrease of serum albumin, total protein, hepatic catalase, and GSH. While the coadministration of carvedilol, crocin and their combination with leflunomide significantly decreased the serum levels of AST, ALT, ALP, hepatic MDA, mTOR gene, PI3K gene, TGF-β, and the pathological changes alongside with the significant elevation of serum albumin, total protein, hepatic catalase, and GSH.This study is suggesting several solutions for Leflunomide-induced hepatotoxicity demonstrated by the protective effect of the antihypertensive drug carvedilol, the natural product crocin, and their combination which was demonstrated to be superior to each drug alone.