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Competing Interests: Disclosures The authors have no conflicts of interest to disclose.

Background: β-Blockers are the most frequently prescribed cardioprotective drugs in hemodialysis (HD) patients, despite their weak evidence. We sought to evaluate the effects of β-blockers on vascular refilling during HD treatments and examine whether carvedilol, for being noncardioselective and poorly dialyzable, associates more impact than others., Methods: The study was performed in a cohort of maintenance HD patients from a tertiary center. All patients had previous β-blocker prescription. We conducted a prospective crossover study and measured vascular refilling volume (Vref) and vascular refilling fraction (Fref) in 2 circumstances: under β-blocker treatment (βb profile) and without β-blocker effect (non-βb profile)., Results: Twenty patients were included, 10 of whom were treated with carvedilol. Predialysis values were comparable between the 2 profiles. Although the βb profile showed lower Vref and higher ABV drop, these differences did not reach statistical significance. Data showed an increase in Fref in the non-βb profile (70.01 ± 6.80% vs. 63.14 ± 11.65%; p = 0.015). The βb profile associated a significantly higher risk of intradialytic hypotension (IDH) (risk ratio 2.40; 95% CI: 1.04-5.55). When analyzing separately the carvedilol group, patients dialyzed under drug effect experienced a significant impairment in Vref, Fref, and refilling rate., Conclusions: Administering β-blockers before HD associated a higher risk of IDH and a decrease in Fref. Patients dialyzed under carvedilol effect showed an impaired refilling, probably related to its noncardioselectivity and lower dializability., (© 2021 The Author(s). Published by S. Karger AG, Basel.)

A decrease in skeletal muscle strength and functional exercise capacity due to aging, frailty, and muscle wasting poses major unmet clinical needs. These conditions are associated with numerous adverse clinical outcomes including falls, fractures, and increased hospitalization. Clenbuterol, a β 2 -adrenergic receptor (β 2 AR) agonist enhances skeletal muscle strength and hypertrophy; however, its clinical utility is limited by side effects such as cardiac arrhythmias mediated by G protein signaling. We recently reported that clenbuterol-induced increases in contractility and skeletal muscle hypertrophy were lost in β-arrestin 1 knockout mice, implying that arrestins, multifunctional adapter and signaling proteins, play a vital role in mediating the skeletal muscle effects of β 2 AR agonists. Carvedilol, classically defined as a βAR antagonist, is widely used for the treatment of chronic systolic heart failure and hypertension, and has been demonstrated to function as a β-arrestin-biased ligand for the β 2 AR, stimulating β-arrestin-dependent but not G protein-dependent signaling. In this study, we investigated whether treatment with carvedilol could enhance skeletal muscle strength via β-arrestin-dependent pathways. In a murine model, we demonstrate chronic treatment with carvedilol, but not other β-blockers, indeed enhances contractile force in skeletal muscle and this is mediated by β-arrestin 1. Interestingly, carvedilol enhanced skeletal muscle contractility despite a lack of effect on skeletal muscle hypertrophy. Our findings suggest a potential unique clinical role of carvedilol to stimulate skeletal muscle contractility while avoiding the adverse effects with βAR agonists. This distinctive signaling profile could present an innovative approach to treating sarcopenia, frailty, and secondary muscle wasting., Competing Interests: The authors declare no competing interest.

Purpose: Increasing cohorts of patients present with diabetic cardiomyopathy, and with no targeted options, treatment often rely on generic pharmaceuticals such as β-blockers. β-blocker efficacy is heterogenous, with second generation β-blocker metoprolol selectively inhibiting β 1 -AR, while third generation β-blocker carvedilol has α 1 -AR inhibition, antioxidant, and anti-apoptotic actions alongside nonselective β-AR inhibition. These additional properties have led to the hypothesis that carvedilol may improve cardiac contractility in the diabetic heart to a greater extent than metoprolol. The present study aimed to compare the efficacy of metoprolol and carvedilol on myocardial function in animal models and cardiac tissue from patients with type 2 diabetes and preserved ejection fraction., Methods: Echocardiographic examination of cardiac function and assessment of myocardial function in isolated trabeculae was carried out in patients with and without diabetes undergoing coronary artery bypass grafting (CABG) who were prescribed metoprolol or carvedilol. Equivalent measures were undertaken in Zucker Diabetic Fatty (ZDF) rats following 4 weeks treatment with metoprolol or carvedilol., Results: Patients receiving carvedilol compared to metoprolol had no difference in cardiac function, and no difference was apparent in myocardial function between β-blockers. Both β-blockers similarly improved myocardial function in diabetic ZDF rats treated for 4 weeks, without significantly affecting in vivo cardiac function., Conclusions: Metoprolol and carvedilol were found to have no effect on cardiac function in type 2 diabetes with preserved ejection fraction, and were similarly effective in preventing myocardial dysfunction in ZDF rats., (© 2020 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.)

The β-blocker carvedilol prevents ultraviolet (UV)-induced skin cancer, but the mechanism is unknown. Since carvedilol possesses antioxidant activity, this study investigated whether carvedilol prevents oxidative photodamage of skin, a precursor event in skin carcinogenesis. The effects of carvedilol, metoprolol (a β-blocker without antioxidant property), and 4-hydroxycarbazole (4-OHC, a carvedilol synthesis intermediate and a free radical scavenger) were compared on UV- or H 2 O 2 -induced cell death and reactive oxygen species (ROS) production in murine epidermal JB6 P+ cells. Although carvedilol attenuated cell death, metoprolol and 4-OHC failed to show protective effects. As expected, increased cellular ROS induced by H 2 O 2 or UV was abolished by carvedilol and 4-OHC, but not by metoprolol. Consistently, carvedilol attenuated the formation of UV-induced cyclobutane pyrimidine dimers (CPDs) and release of prostaglandin E 2 in JB6 P+ cells. Carvedilol's activity was further confirmed in full thickness 3D human reconstituted skin, where carvedilol attenuated UV-mediated epidermal thickening, the number of Ki-67 and p53 positive cells as well as CPD formation. Based on pathway-specific Polymerase Chain Reaction (PCR) Array analysis, carvedilol treatment in many cases normalized UV-induced expression changes in DNA repair genes. Thus, carvedilol's photoprotective activity is not attributed to β-blockade or direct ROS-scavenging capacity, but likely via DNA repair regulation., Competing Interests: The authors declare no conflicts of interest.

Staphylococcus aureus infections are common and difficult to treat. The increasing number of drug-resistant staphylococcal infections has created the need to develop new strategies for the treatment of these infections. The synergistic antimicrobial activity of different pharmaceuticals seems to be an interesting alternative. The aim of this study was to assess the synergistic activity of ciprofloxacin and carvedilol against S. aureus strains. The antibacterial potential of ciprofloxacin and carvedilol was evaluated according to the CLSI guidelines. The calcium content in S. aureus cells was measured using flow cytometry and atomic absorption spectroscopy. Moreover, confocal and scanning electron microscopy were used to determine the mechanism of antibacterial synergy of ciprofloxacin and carvedilol. The antibacterial effect of ciprofloxacin was higher in the presence of carvedilol than in S. aureus cultures containing the antibiotic only. A significant increase in S. aureus membrane permeability was also observed. The simultaneous administration of the tested compounds caused damage to S. aureus cells visualized by SEM. Enhancement of the antimicrobial action of ciprofloxacin by carvedilol was correlated with an increase in free calcium content in S. aureus cells, morphological changes to the cells, and a reduction in the ability to form bacterial aggregates.

Background: The comparative tolerability, efficacy, and safety of bisoprolol and carvedilol have not been established in Japanese patients with heart failure and reduced ejection fraction (HFrEF)., Methods and results: The CIBIS-J trial is a multicenter, open-label, non-inferiority randomized controlled trial of bisoprolol vs. carvedilol in 217 patients with HFrEF (EF ≤40%). The primary endpoint was tolerability, defined as reaching and maintaining the maximum maintenance dose (bisoprolol 5 mg/day or carvedilol 20 mg/day) during 48 weeks of treatment. The primary endpoint was achieved in 41.4% of patients in bisoprolol (n=111) and 42.5% in carvedilol (n=106) groups. The non-inferiority of tolerability of bisoprolol compared with carvedilol was not supported, however, neither β-blocker was superior with regard to tolerability. Heart rate (HR) decreased in both groups and its decrease from baseline was significantly greater in the bisoprolol group (20.3 vs. 15.4 beats/min at 24 week, P<0.05). Plasma B-type natriuretic peptide (BNP) levels decreased in both groups and the decrease was significantly greater in the carvedilol group (12.4 vs. 39.0 % at 24 weeks, P<0.05)., Conclusions: There were no significant differences between bisoprolol and carvedilol in the tolerability of target doses in Japanese HFrEF patients. The clinical efficacy and safety were also similar despite the greater reduction in HR by bisoprolol and plasma BNP by carvedilol.

Aims/hypothesis: This study evaluates whether the non-selective β-blocker, carvedilol, can be used to prevent counterregulatory failure and the development of impaired awareness of hypoglycaemia (IAH) in recurrently hypoglycaemic rats., Methods: Sprague Dawley rats were implanted with vascular catheters and intracranial guide cannulas targeting the ventromedial hypothalamus (VMH). These animals underwent either three bouts of insulin-induced hypoglycaemia or received three saline injections (control group) over 3 days. A subgroup of recurrently hypoglycaemic animals was treated with carvedilol. The next day, the animals underwent a hypoglycaemic clamp with microdialysis without carvedilol treatment to evaluate changes in central lactate and hormone levels. To assess whether carvedilol prevented IAH, we treated rats that had received repeated 2-deoxyglucose (2DG) injections to impair their awareness of hypoglycaemia with carvedilol and measured food intake in response to insulin-induced hypoglycaemia as a surrogate marker for hypoglycaemia awareness., Results: Compared with the control group, recurrently hypoglycaemic rats had a ~1.7-fold increase in VMH lactate and this was associated with a 75% reduction in the sympathoadrenal response to hypoglycaemia. Treatment with carvedilol restored VMH lactate levels and improved the adrenaline (epinephrine) responses. In 2DG-treated rats compared with control animals receiving saline, food intake was reduced in response to hypoglycaemia and increased with carvedilol treatment., Conclusions/interpretation: We conclude that carvedilol may be a useful therapy to prevent counterregulatory failure and improve IAH.

Recent studies suggest that the β-blocker drug carvedilol prevents skin carcinogenesis but the mechanism is unknown. Carvedilol is one of a few β-blockers identified as biased agonist based on an ability to promote β-arrestin-mediated processes such as ERK phosphorylation. To understand the role of phosphoproteomic signaling in carvedilol's anticancer activity, the mouse epidermal JB6 P+ cells treated with EGF, carvedilol, or their combination were analyzed using the Phospho Explorer Antibody Array containing 1318 site-specific and phospho-specific antibodies of over 30 signaling pathways. The array data indicated that both EGF and carvedilol increased phosphorylation of ERK's cytosolic target P70S6 K while its nuclear target ELK-1 were activated only by EGF; Furthermore, EGF-induced phosphorylation of ELK-1 and c-Jun was attenuated by carvedilol. Subcellular fractionation analysis indicated that ERK nuclear translocation induced by EGF was blocked by co-treatment with carvedilol. Western blot and luciferase reporter assays confirmed that the biased β-blockers carvedilol and alprenolol blocked EGF-induced phosphorylation and activation of c-Jun/AP-1 and ELK-1. Consistently, both carvedilol and alprenolol strongly prevented EGF-induced neoplastic transformation of JB6 P+ cells. Remarkably, oral carvedilol treatment significantly inhibited the growth of A375 melanoma xenograft in SCID mice. As nuclear translocation of ERK is a key step in carcinogenesis, inhibition of this event is proposed as a novel anticancer mechanism for biased β-blockers such as carvedilol., (© 2018 Wiley Periodicals, Inc.)

The R-carvedilol enantiomer, present in the racemic mixture of the chiral drug carvedilol, does not bind to the β-adrenergic receptors, but exhibits skin cancer preventive activity. For skin delivery, R-carvedilol-loaded transfersomes were prepared using various ratios of drug, lipids, and surfactants, and characterized for particle size, zeta potential, encapsulation efficiency, stability, and morphology. Transfersomes were compared for in vitro drug release and ex vivo skin penetration and retention. Skin irritation was evaluated by viability assay on murine epidermal cells and reconstructed human skin culture. Single-dose and repeated-dose dermal toxicity was determined in SKH-1 hairless mice. Efficacy was evaluated in SKH-1 mice exposed to single or multiple ultraviolet (UV) radiations. Transfersomes released the drug at a slower rate, but significantly increased skin drug permeation and retention compared with the free drug. The transfersome with a drug-lipid-surfactant ratio of 1:3:0.5 (T-RCAR-3) demonstrated the highest skin drug retention and was selected for further studies. T-RCAR-3 at 100 µM did not induce skin irritation in vitro and in vivo. Topical treatment with T-RCAR-3 at 10 µM effectively attenuated acute UV-induced skin inflammation and chronic UV-induced skin carcinogenesis. This study demonstrates feasibility of using R-carvedilol transfersome for preventing UV-induced skin inflammation and cancer.

Rational & objectiveBeta-blockers are recommended for patients with heart failure (HF) but their benefit in the dialysis population is uncertain. Beta-blockers are heterogeneous, including with respect to their removal by hemodialysis. We sought to evaluate whether β-blocker use and their dialyzability characteristics were associated with early mortality among patients with chronic kidney disease with HF who transitioned to dialysis.Study designRetrospective cohort study.Setting & participantsAdults patients with chronic kidney disease (aged≥18 years) and HF who initiated either hemodialysis or peritoneal dialysis during January 1, 2007, to June 30, 2016, within an integrated health system were included.ExposuresPatients were considered treated with β-blockers if they had a quantity of drug dispensed covering the dialysis transition date.OutcomesAll-cause mortality within 6 months and 1 year or hospitalization within 6 months after transition to maintenance dialysis.Analytical approachInverse probability of treatment weights using propensity scores was used to balance covariates between treatment groups. Cox proportional hazard analysis and logistic regression were used to investigate the association between β-blocker use and study outcomes.Results3,503 patients were included in the study. There were 2,115 (60.4%) patients using β-blockers at transition. Compared with nonusers, the HR for all-cause mortality within 6 months was 0.79 (95% CI, 0.65-0.94) among users of any β-blocker and 0.68 (95% CI, 0.53-0.88) among users of metoprolol at transition. There were no observed differences in all-cause or cardiovascular-related hospitalization.LimitationsThe observational nature of our study could not fully account for residual confounding.ConclusionsBeta-blockers were associated with a lower rate of mortality among incident hemodialysis patients with HF. Similar associations were not observed for hospitalizations within the first 6 months following transition to dialysis.

Melanoma is an aggressive skin cancer. Increasing evidence has shown the role of β-adrenergic receptors in the pathogenesis of melanoma. Carvedilol is a widely used non-selective β-AR antagonist with potential anticancer activity. The purpose of the study was to estimate the influence of carvedilol and sorafenib alone and in combination on the growth and inflammatory response of C32 and A2058 melanoma cells. Furthermore, this study also aimed to predict the probable interaction of carvedilol and sorafenib when administered together. Predictive study of the interaction of carvedilol and sorafenib was performed using the ChemDIS-Mixture system. Carvedilol and sorafenib alone and in combination showed a growth inhibitory effect on cells. The greatest synergistic antiproliferative effect on both cell lines was observed at Car 5 μM combined with Sor 5 μM. Analysis in silico identified diseases, proteins, and metabolic pathways that can be affected by the interaction of carvedilol and sorafenib. The results obtained demonstrated that carvedilol and sorafenib modulated the secretion of IL-8 by IL-1β-stimulated by melanoma cell lines but the use of a combination of both drugs did not intensify the effect. In summary, the results presented indicate that the combination of carvedilol and sorafenib may have a promising anticancer effect on melanoma cells.

The β-blocker carvedilol has been shown to prevent skin carcinogenesis in vitro and in vivo. Since systemic absorption of the β-blocker may cause cardiovascular disturbance, we developed a carvedilol loaded transfersome for skin-targeted delivery. Transfersomes were prepared using phospholipids and surfactants at various ratios and characterized. One formulation (F18) selected for further analysis was composed of carvedilol, soy phosphatidylcholine, and Tween-80 at a ratio of 1:3:0.5, which had a particle size of 115.6 ± 8.7 nm, a zeta potential of 11.34 ± 0.67 mV, and an encapsulation efficiency of 93.7 ± 5.1%. F18 inhibited EGF-induced neoplastic transformation of mouse epidermal JB6 P+ cells at non-toxic concentrations, while only high concentrations induced cytotoxicity in JB6 P+ and human keratinocytes HaCaT. Compared to the free drug, F18 released through the dialysis membrane and permeated through the porcine ear skin at a slower rate, but similarly depositing the drug in the epidermis and dermis of the skin. Consistently, surface application of F18 on reconstructed full-thickness human skin showed slower drug permeation, while it suppressed ultraviolet-induced DNA damage, inflammatory gene expression, and apoptosis. These data indicate that transfersome is a promising topical delivery system of carvedilol for preventing ultraviolet-induced skin damage and carcinogenesis.

Melanoma is an aggressive skin cancer. Increasing evidence has shown the role of β-adrenergic receptors in the pathogenesis of melanoma. Carvedilol is a widely used non-selective β-AR antagonist with potential anticancer activity. The purpose of the study was to estimate the influence of carvedilol and sorafenib alone and in combination on the growth and inflammatory response of C32 and A2058 melanoma cells. Furthermore, this study also aimed to predict the probable interaction of carvedilol and sorafenib when administered together. Predictive study of the interaction of carvedilol and sorafenib was performed using the ChemDIS-Mixture system. Carvedilol and sorafenib alone and in combination showed a growth inhibitory effect on cells. The greatest synergistic antiproliferative effect on both cell lines was observed at Car 5 μM combined with Sor 5 μM. Analysis in silico identified diseases, proteins, and metabolic pathways that can be affected by the interaction of carvedilol and sorafenib. The results obtained demonstrated that carvedilol and sorafenib modulated the secretion of IL-8 by IL-1β-stimulated by melanoma cell lines but the use of a combination of both drugs did not intensify the effect. In summary, the results presented indicate that the combination of carvedilol and sorafenib may have a promising anticancer effect on melanoma cells. [ABSTRACT FROM AUTHOR]

Simple Summary: Benzo(a)pyrene is a ubiquitously present environmental contaminant that induces lung cancer after being converted into active metabolites via aryl hydrocarbon receptor (AhR)-mediated metabolic activation. Previous reports showed that carvedilol is one of the most effective β-blockers with skin cancer preventive activity. The current study evaluated the effect and mechanism of carvedilol on benzo(a)pyrene-induced lung toxicity, inflammation and carcinogenesis. Carvedilol blocked the benzo(a)pyrene-induced malignant transformation of human bronchial epithelial cells and inhibited the benzo(a)pyrene-induced activation of the oncogenic signaling of ELK-1, NF-κB and AhR. This result suggests that the cross-talk of these signaling pathways plays an important role in mediating both inflammation and carcinogenesis in the lung. Carvedilol's activity was further confirmed on mouse models of acute lung toxicity and inflammation, as well as chronic lung cancer development induced by benzo(a)pyrene. As an FDA-approved generic drug, carvedilol may be repurposed as a lung cancer preventive agent. The current study evaluated the effects of the β-blocker carvedilol on benzo(a)pyrene (B(a)P) and its active metabolite benzo(a)pyrene diol epoxide (BPDE)-induced lung toxicity, inflammation and carcinogenesis and explored the potential mechanisms. Carvedilol blocked the BPDE-induced malignant transformation of human bronchial epithelial cells BEAS-2B. In BEAS-2B cells, B(a)P strongly activated ELK-1, a transcription factor regulating serum response element (SRE) signaling, which was attenuated by carvedilol. Carvedilol also inhibited the B(a)P-induced AhR/xenobiotic responsive element (XRE) and mRNA expression of CYP1A1 and attenuated B(a)P-induced NF-κB activation. In a B(a)P-induced acute lung toxicity model in CD-1/IGS mice, pretreatment with carvedilol for 7 days before B(a)P exposure effectively inhibited the B(a)P-induced plasma levels of lactate dehydrogenase and malondialdehyde, inflammatory cell infiltration and histopathologic abnormalities in the lung, and upregulated the expression of GADD45α, caspase-3 and COX-2 in the lung. In a B(a)P-induced lung carcinogenesis model in A/J mice, carvedilol treatment for 20 weeks did not affect body weight but significantly attenuated tumor multiplicity and volume. These data reveal a previously unexplored role of carvedilol in preventing B(a)P-induced lung inflammation and carcinogenesis by inhibiting the cross-talk of the oncogenic transcription factors ELK-1, AhR and NF-κB. [ABSTRACT FROM AUTHOR]

Elham Shirazi-Tehrani,1 Negar Firouzabadi,1,2 Gholamhossein Tamaddon,3,4 Ehsan Bahramali,5 Asma Vafadar3,4 1Department of Pharmacology & Toxicology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran; 2Noncommunicable Diseases Research Center, Fasa University of Medical Sciences, Fasa, Iran; 3Department of Medical Biotechnology, School of Paramedical Sciences, Shiraz University of Medical Sciences, Shiraz, Iran; 4Diagnostic Laboratory Sciences and Technology Research Center, School of Paramedical Sciences, Shiraz University of Medical Sciences, Shiraz, Iran; 5Digestive Disease Research Center, Digestive Disease Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran, IranCorrespondence: Negar FirouzabadiDepartment of Pharmacology & Toxicology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, IranTel +98-917-314-5303Email nfirouzabadi@yahoo.comGholamhossein TamaddonDepartment of Medical Biotechnology, School of Paramedical Sciences, Shiraz University of Medical Sciences, Shiraz, IranTel +98-915-141-7043Email tamaddon.g@gmail.comIntroduction: MicroRNAs (miRNAs) are recognized as major contributors in various cardiovascular diseases, such as heart failure (HF). These small noncoding RNAs that posttranscriptionally control target genes are involved in regulating different pathophysiological processes including cardiac proliferation, ifferentiation, hypertrophy, and fibrosis. Although carvedilol, a β-adrenergic blocker, and a drug of choice in HF produce cytoprotective actions against cardiomyocyte hypertrophy, the mechanisms are poorly understood. Here we proposed that the expression of hypertrophic-specific miRNAs (miR-1, miR-133, miR-208, and miR-214) might be linked to beneficial effects of carvedilol.Methods: The levels of four hypertrophic-specific miRNAs were measured in the sera of 35 patients with systolic HF receiving carvedilol (treated) and 20 HF patients not receiving any β-blockers (untreated) as well as 17 nonHF individuals (healthy) using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Systolic HF was defined as left ventricular ejection fraction < 50% by transthoracic echocardiography.Results: We demonstrated that miR-1 and miR-214 were significantly upregulated in the treated group compared to the untreated group (P=0.014 and 5.3-fold, 0.033 and 4.2-fold, respectively). However, miR-133 and miR-208 did not show significant difference in expression between these two study groups. MiR-1 was significantly downregulated in the untreated group compared with healthy individuals (P=0.019 and 0.14-fold).Conclusion: In conclusion, it might be postulated that one of the mechanisms by which carvedilol may exert its cardioprotective effects can be through increasing miR-1 and miR-214 expressions which may also serve as a potential therapeutic target in patients with systolic HF in future.Keywords: microRNA, β-blocker, carvedilol, systolic heart failure, cardiac hypertrophy

Negar Firouzabadi,1– 3 Maryam Dashti,1 Ali Dehshahri,4 Ehsan Bahramali5 1Department of Pharmacology and Toxicology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran; 2Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran; 3Noncommunicable Diseases Research Center, Fasa University of Medical Sciences, Fasa, Iran; 4Department of Pharmaceutical Biotechnology, Shiraz University of Medical Sciences, Shiraz, Iran; 5Digestive Disease Research Center, Digestive Disease Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran, IranCorrespondence: Negar FirouzabadiDepartment of Pharmacology and Toxicology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, IranTel +98-917-314-5303Fax +98-713-2424128Email nfirouzabadi@yahoo.comObjective: The IL-33/ST2 pathway plays a fundamental role in the cardiovascular system and can be considered as a new therapeutic strategy for the treatment or prevention of cardiovascular diseases. ST2, as an interleukin (IL)-1 receptor family member, has transmembrane (ST2L) and soluble (sST2) isoforms. sST2 neutralizes IL-33 and thereby inhibits the cardioprotective role of IL-33/ST2L signaling pathway. Increase in sST2 level is associated with weak cardiac output and can be a predictor of mortality in heart failure (HF). Thereby, we hypothesized that there may be a relationship between the cardioprotective effects of carvedilol and sST2 and IL-3 in HF patients.Methods: sST2 and IL-33 were measured in serum of 66 individuals; 22 healthy volunteers and 44 suffering from HF; among whom 25 patients received carvedilol and the other 19 patients did not receive any β-blockers.Results: Lack of association between serum levels of IL-33 and sST2 was observed between HF patients and healthy individuals (2.4466 ± 0.69 vs 2.6748 ± 0.33 and 3416.6 ± 1089.1 vs 2971.6 ± 792.5, respectively). Our results indicated no significant difference between sST2 and IL-33 levels in HF patients who did not receive beta-blockers and patients receiving carvedilol (P=0.59 and P=0.97).Conclusion: Our results showed a lack of association between serum levels of IL-33 and sST2 and HF. Moreover, the results do not confirm the cardioprotective mechanism of carvedilol by means of IL-33/sST2 pathway.Keywords: heart failure, IL-33, sST2, carvedilol, β-blocker, biomarker

The R-carvedilol enantiomer, present in the racemic mixture of the chiral drug carvedilol, does not bind to the β-adrenergic receptors, but exhibits skin cancer preventive activity. For skin delivery, R-carvedilol-loaded transfersomes were prepared using various ratios of drug, lipids, and surfactants, and characterized for particle size, zeta potential, encapsulation efficiency, stability, and morphology. Transfersomes were compared for in vitro drug release and ex vivo skin penetration and retention. Skin irritation was evaluated by viability assay on murine epidermal cells and reconstructed human skin culture. Single-dose and repeated-dose dermal toxicity was determined in SKH-1 hairless mice. Efficacy was evaluated in SKH-1 mice exposed to single or multiple ultraviolet (UV) radiations. Transfersomes released the drug at a slower rate, but significantly increased skin drug permeation and retention compared with the free drug. The transfersome with a drug–lipid–surfactant ratio of 1:3:0.5 (T-RCAR-3) demonstrated the highest skin drug retention and was selected for further studies. T-RCAR-3 at 100 µM did not induce skin irritation in vitro and in vivo. Topical treatment with T-RCAR-3 at 10 µM effectively attenuated acute UV-induced skin inflammation and chronic UV-induced skin carcinogenesis. This study demonstrates feasibility of using R-carvedilol transfersome for preventing UV-induced skin inflammation and cancer.

In this issue of the Clinical Kidney Journal , Wu et al. present the results of a nationwide population-based study using Taiwanese administrative data to compare safety and efficacy outcomes with initiation of bisoprolol versus carvedilol among patients receiving maintenance hemodialysis for >90 days. The primary outcomes were all-cause mortality and major adverse cardiovascular events over 2 years of follow-up. The study found that bisoprolol was associated with a lower risk for both major adverse cardiovascular events and all-cause mortality compared with carvedilol. While the bulk of the existing evidence favors a cardioprotective and survival benefit with β-blockers as a medication class among dialysis patients, there is wide heterogeneity among specific β-blockers in regard to pharmacologic properties and dialyzability. While acknowledging the constraints of observational data, these findings may serve to inform clinicians about the preferred β-blocker agent for dialysis patients to help mitigate cardiovascular risk and improve long-term survival for this high-risk population. [ABSTRACT FROM AUTHOR]

Abstract Purpose Increasing cohorts of patients present with diabetic cardiomyopathy, and with no targeted options, treatment often rely on generic pharmaceuticals such as β‐blockers. β‐blocker efficacy is heterogenous, with second generation β‐blocker metoprolol selectively inhibiting β1‐AR, while third generation β‐blocker carvedilol has α1‐AR inhibition, antioxidant, and anti‐apoptotic actions alongside nonselective β‐AR inhibition. These additional properties have led to the hypothesis that carvedilol may improve cardiac contractility in the diabetic heart to a greater extent than metoprolol. The present study aimed to compare the efficacy of metoprolol and carvedilol on myocardial function in animal models and cardiac tissue from patients with type 2 diabetes and preserved ejection fraction. Methods Echocardiographic examination of cardiac function and assessment of myocardial function in isolated trabeculae was carried out in patients with and without diabetes undergoing coronary artery bypass grafting (CABG) who were prescribed metoprolol or carvedilol. Equivalent measures were undertaken in Zucker Diabetic Fatty (ZDF) rats following 4 weeks treatment with metoprolol or carvedilol. Results Patients receiving carvedilol compared to metoprolol had no difference in cardiac function, and no difference was apparent in myocardial function between β‐blockers. Both β‐blockers similarly improved myocardial function in diabetic ZDF rats treated for 4 weeks, without significantly affecting in vivo cardiac function. Conclusions Metoprolol and carvedilol were found to have no effect on cardiac function in type 2 diabetes with preserved ejection fraction, and were similarly effective in preventing myocardial dysfunction in ZDF rats.

L'hypoglycémie est le principal effet indésirable rapporté avec les sulfamides hypoglycémiants. Elle peut déclencher une tachycardie que le carvédilol, en raison de son effet β-bloquant, est à même de masquer. L'association gliclazide et carvédilol exige des précautions d'emploi. L'autosurveillance glycémique doit être renforcée et le pharmacien d'officine doit rappeler au patient l'importance de savoir détecter une hypoglycémie et réaliser un resucrage rapide par voie orale. Hypoglycemia is the main adverse effect reported with hypoglycemic sulfonamides. It can trigger tachycardia, which carvedilol, because of its β-blocking effect, is able to mask. The combination of gliclazide and carvedilol requires precautions. Self-monitoring of blood glucose levels must be reinforced and the pharmacist must remind the patient of the importance of knowing how to detect hypoglycemia and how to quickly adjust blood sugar levels by mouth. [ABSTRACT FROM AUTHOR]

Background: The selection of β-blocker for survivors after primary intervention due to acute ST-elevation myocardial infarction seems crucial to improve the outcomes. However, rare comparison data existed for these patients. We aimed to compare the effectiveness of selective β-blockers to that of carvedilol in patients treated with primary intervention. Methods and results: Among the 1,485 patients in the "INTERSTELLAR" registry between 2007 and 2015, 238 patients with selective β-blockers (bisoprolol, nebivolol, atenolol, bevantolol, and betaxolol) and 988 with carvedilol were included and their clinical outcomes were compared for a 2-year observation period. In the clinical baseline characteristics, the unfavorable trends in the carvedilol group were high Killip presentation, lower ejection fractions, smaller diameters, and longer lengths of deployed stents. Although mortality (2.5% vs. 1.7%; p = 0.414) and the rate of stroke (0.8% vs. 0.6%; p = 0.693) were not different between groups, the rate of recurrent myocardial infarction (4.6% vs. 1.2%; p = 0.001) and of target vessel revascularization (4.2% vs. 0.9%; p < 0.001) were lower in the carvedilol group. After eliminating the difference by propensity matching, the similar outcome result was shown (all-cause death, 0.6% vs. 1.0%, p = 0.678; stroke, 0.6% vs. 1.2%, p = 0.479; myocardial infarction, 5.0% vs. 1.2%, p = 0.003; target vessel revascularization, 4.5% vs. 0.7%, p < 0.006) for 595 matched populations. The use of carvedilol was also determined to be an independent predictor for recurrent myocardial infarctions (hazard ratio = 0.305; p = 0.005; 95% confidence interval = 0.13-0.69). Conclusion: Use of a carvedilol in ST-segment myocardial infarction survivor is associated with lower recurrent myocardial infarction events. Thus, it might be the better choice of β-blocker for secondary prevention in ST-elevation myocardial infarction patients treated with primary percutaneous coronary intervention. [ABSTRACT FROM AUTHOR]

The β-blocker carvedilol has been shown to prevent skin carcinogenesis in vitro and in vivo. Since systemic absorption of the β-blocker may cause cardiovascular disturbance, we developed a carvedilol loaded transfersome for skin-targeted delivery. Transfersomes were prepared using phospholipids and surfactants at various ratios and characterized. One formulation (F18) selected for further analysis was composed of carvedilol, soy phosphatidylcholine, and Tween-80 at a ratio of 1:3:0.5, which had a particle size of 115.6 ± 8.7 nm, a zeta potential of 11.34 ± 0.67 mV, and an encapsulation efficiency of 93.7 ± 5.1%. F18 inhibited EGF-induced neoplastic transformation of mouse epidermal JB6 P+ cells at non-toxic concentrations, while only high concentrations induced cytotoxicity in JB6 P+ and human keratinocytes HaCaT. Compared to the free drug, F18 released through the dialysis membrane and permeated through the porcine ear skin at a slower rate, but similarly depositing the drug in the epidermis and dermis of the skin. Consistently, surface application of F18 on reconstructed full-thickness human skin showed slower drug permeation, while it suppressed ultraviolet-induced DNA damage, inflammatory gene expression, and apoptosis. These data indicate that transfersome is a promising topical delivery system of carvedilol for preventing ultraviolet-induced skin damage and carcinogenesis.

Many drugs used to treat non-infectious diseases have also shown excellent antibacterial activity or the ability to enhance the action of antibiotics. The aim of this study was to investigate the antibacterial activity of a popular β-blocker, carvedilol, and its mechanism of antibacterial action. The antibacterial activity of carvedilol was evaluated using the microdilution method and its influence on the viability of bacterial cells was investigated by the alamarBlue ® test. Changes in phospholipid and fatty acid composition were analysed using LC-MS/MS and GC-MS techniques. The permeability of bacterial cell membranes following exposure to carvedilol was studied using propidium iodide staining and confocal microscopy. The ability of the tested bacteria to degrade carvedilol was examined by LC-MS/MS. In this study, the antibacterial activity of carvedilol is described for the first time, with a decrease in the viability of all assayed bacteria observed following treatment with the β-blocker. Staphylococcus aureus and Staphylococcus epidermidis were found to be the most sensitive among the tested strains. Significant modifications to fatty acid composition were observed in S. aureus incubated with carvedilol. Moreover, the cell membrane permeability of bacteria incubated with carvedilol was higher for Gram-positive bacteria than for Gram-negative bacteria. Furthermore, Gram-negative Escherichia coli and Pseudomonas aeruginosa strains, which were highly resistant to carvedilol, exhibited an ability to eliminate carvedilol from the growth medium. In addition, three carvedilol metabolites were identified in E. coli and P. aeruginosa cultures. The antibacterial activity of carvedilol may suggest its potential usefulness in the synthesis of new antibacterial drugs. [ABSTRACT FROM AUTHOR]

Beta-adrenergic blocking agents like carvedilol are widely detected environmental pollutants. Its human metabolism is well known, while the fate of the carvedilol when metabolized by environmental strains is unknown. The aim of this study was to investigate the mechanism and pathways of carvedilol metabolism by the common environmental fungal strain Cunninghamella elegans . In this report the process of carvedilol biotransformation by C. elegans was described for the first time. A total of ten carvedilol derivatives were identified in C. elegans cultures. Similarly to mammalian metabolism of carvedilol, its fungal biotransformation proceeded through hydroxylation and conjugation reactions. However, in C. elegans cultures new products such as methyl-phenyl carvedilol and glucose-desmethyl carvedilol were identified, which had not been previously detected in human and animals. Moreover, an involvement of cytochrome P450 and cytochrome P450 reductase in carvedilol fungal metabolism was revealed. [ABSTRACT FROM AUTHOR]

Beta adrenergic antagonists like carvedilol are typical environmental pollutants detected in wastewater and surface water. Human metabolism of carvedilol is well investigated, while its environmental fates are still unknown. In recent years, there have been appearing reports on high toxicity of β-blockers toward aquatic organisms. In this paper the ability of the filamentous fungus C. echinulata to eliminate the β-blocker has been described for the first time. An 83% loss of carvedilol was observed after 120 h incubation of the tested fungus with the compound, where hydroxylated carvedilol metabolites were identified as the major biotransformation products. Carvedilol degradation by C. echinulata was proceeded by hydroxylation and conjugation reactions similar to its mammalian metabolism. Glucose conjugate was found in the fungi cultures, whereas glucuronide conjugates were detected in mammals. The impact of carvedilol on the functionality of fungal cells was also evaluated. A 2-fold decrease in the PC/PE ratio was noticed in the C. echinulata cell membrane after the exposition to carvedilol compared to control mycelium incubated without the β-blocker. The change can denote perturbation of fungal cell membrane integration by carvedilol. Moreover, 2.8-fold lower toxicity of postcultures supernatants toward D. magna were shown in contrast to abiotic control. [ABSTRACT FROM AUTHOR]

Background and Aims: Carvedilol ((+/-)-1-(carbazol-4-yloxy)-3-[[2-(o-methoxyphenoxy)ethyl]amino]-2-propanol), a β-adrenoceptor-blocker, has multi-channel blocking and vasodilator properties. This agent dose-dependently improves left ventricular function and reduces mortality in patients with arrhythmia and chronic heart failure. However, the effect of carvedilol on the cardiac Na+/Ca2+exchanger (NCX1) has not been investigated. Methods and Results: We examined the effects of carvedilol and metoprolol, 2 β-blockers, on Na+/Ca2+ exchange current (INCX) in guinea-pig cardiac ventricular cells and fibroblasts expressing dog cardiac NCX1. Carvedilol suppressed INCX in a concentration-dependent manner but metoprolol did not. IC50 values for the Ca2+ influx (outward) and efflux (inward) components of INCX were 69.7 and 61.5 µmol/l, respectively. Carvedilol at 100 µmol/l inhibited INCX in CCL39 cells expressing wild type NCX1 similar to mutant NCX1 without the intracellular regulatory loop. Carvedilol at 30 µmol/l abolished ouabain-induced delayed afterdepolarizations. Conclusion: Carvedilol inhibited cardiac NCX in a concentration-dependent manner in isolated cardiac ventricles, but metoprolol did not. We conclude that carvedilol inhibits NCX1 at supratherapeutic concentrations. [ABSTRACT FROM AUTHOR]

The construction and performance characteristics of a novel potentiometric carbon paste electrode based on incorporation of the ion-association complex of the carvedilol-phosphotungstate were studied. The electrode exhibited Nernstian slope of 58.7 mV/decade to carvedilol over a wide concentration range from 3.0 × 10 −7 to 1.0 × 10 −3 M with low detection limit of 1.5 × 10 −7 M. The proposed sensor manifested advantages of fast response, long life time, and most importantly, good selectivities for carvedilol relative to a wide variety of common foreign inorganic cations, biological species and other β-blockers. The advantages of the new sensor were compared to the characteristics of previously reported traditional liquid inner contact PVC membrane electrode. The sensor was successfully applied as an indicator electrode in potentiometric titration and potentiometric determination of carvedilol in carvedilol tablet, blood serum and urine samples. The inclusion complex formation between α- and β-cyclodextrin and carvedilol was studied potentiometrically by the proposed sensor and formation constant of the inclusion complexes were calculated. [ABSTRACT FROM AUTHOR]

Background: We evaluated the effect of coadministration of β-blocker (carvedilol) as the third agent with angiotensin II receptor blockers (ARB) and calcium channel blockers (CCB) on blood pressure (BP) regulation and glucose metabolism. Methods: Diabetic patients who did not achieve the therapeutic BP goal (140/90 mmHg) by ARB and CCB combination therapy were recruited. This study was designed to compare the BP regulating effects by adding carvedilol (10 mg/day, n=30) and by doubling the dose of either ARB (n=34) or CCB (n=31). Serum glucose metabolism was examined. Results: The carvedilol group showed a decrease (P<0.01) in BP from 166±11/90±8 to 156±9/84±7 mmHg at 12 weeks. In the ARB and CCB groups, BP also decreased (P<0.01) from 164±11/87±8 to 153±10/83±8 and 163±7/87±8 to 153±8/84±9 mmHg at 12 weeks. The rates of achieving therapeutic goal at 12 weeks were 36.7% in the carvedilol, 38.2% in the ARB and 41.9% in the CCB group. Serum glucose metabolism did not change in all groups. Conclusions: These results suggest that adding carvedilol decreased BP as safely as increasing the dose of ARB or CCB in patients with diabetic nephropathy. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

β-blockers are effective antihypertensive agents and, together with diuretics, have been the cornerstone of pioneering studies showing their benefits on cardiovascular morbidity and mortality as a consequence of blood pressure reduction in patients with hypertension. However, evidence from recent meta-analyses have demonstrated no benefit afforded by atenolol compared with placebo in risk of mortality, myocardial infarction, or stroke, and a higher risk of mortality and stroke with atenolol/propranolol compared with other antihypertensive drug classes. Thus, the effect of these agents on cardiovascular morbidity and mortality in hypertensive patients, especially their use in uncomplicated hypertension, has remained largely controversial. However, it is recognized that the clinical studies used in these meta-analyses were mainly based on the older second-generation β-blockers, such as atenolol and metoprolol. Actually, considerable heterogeneity in, eg, pharmacokinetic, pharmacological, and physicochemical properties exists across the different classes of β-blockers, particularly between the second-generation and newer third-generation agents. Carvedilol is a vasodilating noncardioselective third-generation β-blocker, without the negative hemodynamic and metabolic effects of traditional β-blockers, which can be used as a cardioprotective agent. Compared with conventional β-blockers, carvedilol maintains cardiac output, has a reduced prolonged effect on heart rate, and reduces blood pressure by decreasing vascular resistance. Studies have also shown that carvedilol exhibits favorable effects on metabolic parameters, eg, glycemic control, insulin sensitivity, and lipid metabolism, suggesting that it could be considered in the treatment of patients with metabolic syndrome or diabetes. The present report provides an overview of the main clinical studies concerning carvedilol administered as either monotherapy or in combination with another antihypertensive or more frequently a diuretic agent, with particular focus on the additional benefits beyond blood pressure reduction. [ABSTRACT FROM AUTHOR]

Beta-adrenolytics are drugs of established position in cardiovascular disorders treatment. Since development of this drug class in the late 50-ties of XX century, they are administered in the therapy of hypertension, coronary artery disease, arrhythmia, myocardial infarct and since several years in heart failure. Carvedilol, novel agent, that has unique properties of β1, β2 and α1 adrenergic receptors blocking has been very well studied in clinical trials. Several side effects of other β-blockers are not observed during carvedilol therapy because of α1 adrenergic receptors blockade. Efficacy of carvedilol in reduction of mortality due to heart failure, coronary artery disease and hypertension was demonstrated in large, randomized, multicenter studies. Some data suggest that carvedilol may beneficially modulate lipid profile and diabetes control. Avedol® is a generic form of carvedilol manufactured by Polpharma S.A. Studies on comparative bioequivalence of carvedilol performed in 2000 revealed any statistically significant differences in such pharmacokinetic parameters as Cmax, Tmax and AUC, moreover relative bioavailability of Avedol® amounted to 103% (confidence interval 90%). [ABSTRACT FROM AUTHOR]

Abstract: Matrix metalloproteinase (MMP) is critical to the progression of atherosclerosis and neointima hyperplasia after vascular injury. We investigated the effects of carvedilol, a pharmacological antioxidant with α- and β-adrenergic blocking activity, on MMP-2 and MMP-9 expression. Vascular injury was induced with the balloon catheters on abdominal aortas of high-cholesterol-fed rabbits. On Day 21, there was significant aortic neointima formation with increased oxidative DNA damage by immunostaining with 8-hydroxy-2′-deoxyguanosine and enhanced MMP-2 and MMP-9 expressions by Western blotting, which were significantly reduced by oral administration of carvedilol (20 mg/kg/day) or probucol (100 mg/kg/day). Vascular expression (by Western blot), activity (by gelatin zymography), and mRNA levels of MMP-2 and MMP-9 were also reduced by carvedilol or probucol. Besides, pretreatment with carvedilol or probucol but not propranolol, a β-blocker, or prazocin, an α-blocker, inhibited tumor necrosis factor-α-stimulated expressions and activities of MMP-2 and MMP-9 in human aortic smooth muscle cells. On electrophoretic mobility-shift assay, carvedilol inhibited the binding activities of activator protein-1 and specific protein-1, two major transcription factors for MMP promoter regions. Accordingly, carvedilol, a pharmacological antioxidant, inhibited in vivo and in vitro expression of MMP-2 and MMP-9 properly by modulating the redox-related pathways, suggesting its potential clinical implications. [Copyright &y& Elsevier]

Abstract: Background: β-blockers are well established for treatment of chronic heart failure (CHF). However, the extent of implementation of trial results and guidelines in daily practice remains limited, and information regarding how patients feel is scarce. Methods: In this prospective observational survey of 6 months duration, 531 physicians from 10 countries recruited 3748 β-blockers untreated patients with CHF. We assessed the efficacy, tolerability and achieved dosage of carvedilol. In addition, patients assessed their well-being 3 times: at baseline, after 3 and 6 months of treatment. Results: Carvedilol was started in 3721 patients with CHF (median age 65 years, 60% men). NYHA class, clinical symptoms and signs, vital signs, 5-item well-being rating scale and visual analogue scale improved during the survey. Side effects, mostly fatigue, hypotension, and dizziness, were reported for 6.5% and 5% of patients at 3 and 6 months and carvedilol had to be discontinued in 63 patients. A total of 55 deaths (1.5%) and 520 hospitalisations in 466 patients (13%) were recorded. At 6 months the mean daily dose of carvedilol was 31±11 mg; 25 mg/day was prescribed to 35% and 50 mg/day to 26% of patients. Conclusions: Initiation and up-titration of carvedilol in ambulatory care patients with CHF is feasible and safe. Its efficacy and tolerability were at least as good as in clinical trials, while the amelioration of patients'' well-being was significant despite sub-optimal dosing. An additional effort should be done by physicians to treat their patients with CHF in daily practice with the recommended β-blockers at optimal doses. [Copyright &y& Elsevier]

Treatment with β-blockers is recommended to achieve and maintain adequate blood pressure control in patients with hypertension, and these agents have been shown to decrease cardiovascular risk factors in patients with both hypertension and type 2 diabetes mellitus. However, β-blocker therapy also may worsen glycemic and lipidemic control and may lead to microalbuminuria. A recent study showed a better metabolic profile with carvedilol than with metoprolol in patients with both type 2 diabetes and hypertension in the presence of renin-angiotensin system blockade. This beneficial effect on metabolic components has been proposed as attributable to carvedilol's α-blocking effects or antioxidant properties. In this article, the pathophysiology of hypertension and type 2 diabetes and the association between them are reviewed, the pharmacologic properties of carvedilol are discussed, and clinical studies in the literature comparing carvedilol with selective β-blockers in patients with both type 2 diabetes and hypertension are identified and evaluated. This information should be useful to practitioners when selecting the optimum β-blocker for treating hypertension in patients with type 2 diabetes. [ABSTRACT FROM AUTHOR]

Abstract: Carvedilol, a β-adrenergic blocker used to treat cardiovascular diseases, protects cell membranes from lipid peroxidative damage. Previous studies suggested the drug resides in a non-polar environment and partitions into cell membranes, perturbing their fluidity. Here differential scanning calorimetry (DSC) and fluorescence spectroscopy were applied to further investigate interactions of carvedilol with a liposome model. Results indicate the association is relatively unaffected by pH or temperature, but could be sensitive to liposome composition. The drug''s carbazole group plays the dominant role in bilayer perturbation. Compared with other β-blockers examined, carvedilol produced the strongest liposome DSC perturbation. Locations of carbazole and carvedilol in the liposome were determined using depth-dependent fluorescent probes. Both compounds are situated in the middle of the bilayer, consistent with strong hydrophobic interactions. This combination of high lipophilicity and specific chemical structure appear required for carvedilol''s novel antioxidant activity, and may enhance cardioprotection. [Copyright &y& Elsevier]

Background: The hypothesis that left ventricular hypertrophy regression in hypertension relates to blood pressure (BP) control and to non-antihypertensive activity of some drugs was tested by comparing the effects of telmisartan and carvedilol on 24-h mean ambulatory BP and left ventricular mass (LVM) regression, measured using three-dimensional echocardiography (3-DECHO) and magnetic resonance imaging (MRI). Methods: A total of 82 patients with mild-to-moderate hypertension and an optimal echocardiographic acoustic window were randomized to receive once-daily telmisartan 80 mg or carvedilol 25 mg for 44 weeks. Results: Ten patients withdrew from the study because office diastolic BP remained >90 mm Hg. The 24-h mean ambulatory systolic/diastolic BP reductions were similar in both treatment groups (telmisartan, from 159.6 ± 10.2/97.8 ± 5.4 to 128.6 ± 6.5/78.2 ± 5.8 mm Hg; carvedilol, from 157.8 ± 11.1/95.7 ± 11.9 to 128.2 ± 5.6/78.7 ± 5.2 mm Hg). However, night-time and last 6-h mean BP reductions were nonsignificantly greater with telmisartan. Using 3-DE, telmisartan (P< .001) and carvedilol (P< .001) progressively reduced LVM index by 21.97 ± 5.84 (15.7%) and 12.31 ± 3.14 (9.1%) g/m2, respectively, at week 44. Similar magnitudes of reductions were observed using MRI (15.5% and 9.6%, respectively). Reductions in LVM index achieved with telmisartan were statistically superior to carvedilol (P≤ .001). Conclusions: The superior LVM regression with telmisartan versus carvedilol suggests telmisartan has a mechanism that may be beyond that of lowering BP in hypertensive patients. [Copyright &y& Elsevier]

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Copyright of Drug Research / Arzneimittel-Forschung (Editio Cantor Verlag fur Medizin und Naturwissenschaften) is the property of Editio Cantor Verlag fur Medizin und Naturwissenschaften and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)