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1.
Int J Cardiol ; 408: 132067, 2024 Aug 01.
Article in English | MEDLINE | ID: mdl-38714235

ABSTRACT

AIMS: The aim of this study is to evaluate the effect of beta-blockers and angiotensin receptor blockers in reducing the aortic growth rate in children with bicuspid aortic valve (BAV)-related aortopathy and ascending phenotype. METHODS: Consecutive paediatric patients (≤16 years) with BAV and ascending aorta (AsAo) dilation (z-score > 3) were enrolled in this observational retrospective cohort study. Patients receiving prophylactic treatment with either atenolol (0.5 to 1.0 mg/kg/daily) or losartan (0.7 to 1.4 mg/kg/daily) were compared with those who did not receive medical prophylaxis (control group). The primary outcome of interest was the annual rate of change in maximal AsAo diameter z-score in the treatment and control groups. RESULTS: From a cohort of 1005 patients, 120 (mean age 11.3 ± 4.5 years, 82% males) fulfilled the inclusion criteria and were included in the study. Patients in the treatment and control group had similar age, sex, family history of BAV, BAV morphology, and baseline AsAo diameter. During a median follow-up of 7.1 years (interquartile range 3.8-10.2), no differences were observed in the annual growth rate of aortic diameter z-score between patients on treatment and controls. The prevalence of aortic diameter progression was similar in the treatment and control groups, and treatment with atenolol or losartan was not associated with a lower rate of aortic disease progression. CONCLUSIONS: The findings revealed no significant difference in the annual aortic growth rate between treated and untreated patients. Larger cohort studies or, ideally, randomized clinical controlled trials are needed to validate these findings.


Subject(s)
Adrenergic beta-Antagonists , Aortic Valve , Bicuspid Aortic Valve Disease , Humans , Male , Female , Child , Retrospective Studies , Adolescent , Adrenergic beta-Antagonists/therapeutic use , Aortic Valve/abnormalities , Aortic Valve/diagnostic imaging , Aortic Valve/pathology , Aortic Valve/drug effects , Angiotensin Receptor Antagonists/therapeutic use , Losartan/therapeutic use , Follow-Up Studies , Cohort Studies , Atenolol/therapeutic use , Treatment Outcome , Aorta/drug effects , Aorta/diagnostic imaging , Aortic Valve Disease/drug therapy , Heart Valve Diseases/drug therapy , Heart Valve Diseases/complications , Angiotensin II Type 1 Receptor Blockers/therapeutic use
2.
Dermatology ; 240(2): 216-225, 2024.
Article in English | MEDLINE | ID: mdl-38228125

ABSTRACT

BACKGROUND: Infants with infantile hemangioma (IH) have been effectively treated with propranolol or atenolol. Concerns were raised about the mental health of these children at school age, due to central nervous system effects of propranolol and visible nature of IH. OBJECTIVE: This study aimed to compare the mental health at school age of children treated with propranolol to children treated with atenolol for IHs and their parents. METHODS: This two-centered cross-sectional study included children aged ≥6 years and treated with either propranolol or atenolol for IH during infancy. Children's outcomes were performance-based affect recognition (Dutch version of the Developmental Neuropsychological Assessment-II [NEPSY-II-NL]), parent-reported emotional and behavioral functioning (Child Behavioral Checklist [CBCL]), and health-related quality of life (KIDSCREEN-27). Parents' outcome was parenting stress (Parenting Stress Questionnaire [OBVL]). RESULTS: Data of 105 children (36 propranolol, 69 atenolol; 6.0-11.8 years) were analyzed. Mental health outcomes did not differ between both ß-blocker groups. Although overall functioning was in line with norms, children presented specific problems concerning affect recognition, parent-reported attention, and social quality of life. Parents showed increased physical symptoms, depressive symptoms, and parent-child relationship problems. CONCLUSION: No difference in mental health at school age was found between children treated with propranolol or atenolol for IH. Although few overall mental health problems were found, specific problems require follow-up. Follow-up of children should be directed toward affect recognition, attention, and social functioning in daily life. Problems reported by parents could be ameliorated by mental health support during and after their infant's ß-blocker treatment.


Subject(s)
Atenolol , Hemangioma, Capillary , Infant , Humans , Child , Atenolol/therapeutic use , Propranolol/therapeutic use , Mental Health , Cross-Sectional Studies , Quality of Life , Hemangioma, Capillary/drug therapy , Adrenergic beta-Antagonists/therapeutic use , Parents
3.
Eur Heart J ; 45(13): 1159-1169, 2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38291599

ABSTRACT

BACKGROUND AND AIMS: Visit-to-visit systolic blood pressure variability (BPV) is an important predictor of cardiovascular (CV) outcomes. The long-term effect of a period of blood pressure (BP) control, but with differential BPV, is uncertain. Morbidity and mortality follow-up of UK participants in the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure-Lowering Arm has been extended for up to 21 years to determine the CV impact of mean systolic blood pressure (SBP) control and BPV during the trial, and amongst those allocated to amlodipine- and atenolol-based treatment. METHODS: Eight thousand five hundred and eighty hypertensive participants (4305 assigned to amlodipine ± perindopril-based and 4275 to atenolol ± diuretic-based treatment during the in-trial period (median 5.5 years) were followed for up to 21 years (median 17.4 years), using linked hospital and mortality records. A subgroup of participants (n = 2156) was followed up 6 years after the trial closure with a self-administered questionnaire and a clinic visit. In-trial mean SBP and standard deviation of visit-to-visit SBP as a measure of BPV, were measured using >100 000 BP measurements. Cox proportional hazard models were used to estimate the risk [hazard ratios (HRs)], associated with (i) mean with SBP and BPV during the in-trial period, for the CV endpoints occurring after the end of the trial and (ii) randomly assigned treatment to events following randomization, for the first occurrence of pre-specified CV outcomes. RESULTS: Using BP data from the in-trial period, in the post-trial period, although mean SBP was a predictor of CV outcomes {HR per 10 mmHg, 1.14 [95% confidence interval (CI) 1.10-1.17], P < .001}, systolic BPV independent of mean SBP was a strong predictor of CV events [HR per 5 mmHg 1.22 (95% CI 1.18-1.26), P < .001] and predicted events even in participants with well-controlled BP. During 21-year follow-up, those on amlodipine-based compared with atenolol-based in-trial treatment had significantly reduced risk of stroke [HR 0.82 (95% CI 0.72-0.93), P = .003], total CV events [HR 0.93 (95% CI 0.88-0.98), P = .008], total coronary events [HR 0.92 (95% CI 0.86-0.99), P = .024], and atrial fibrillation [HR 0.91 (95% CI 0.83-0.99), P = .030], with weaker evidence of a difference in CV mortality [HR 0.91 (95% CI 0.82-1.01), P = .073]. There was no significant difference in the incidence of non-fatal myocardial infarction and fatal coronary heart disease, heart failure, and all-cause mortality. CONCLUSIONS: Systolic BPV is a strong predictor of CV outcome, even in those with controlled SBP. The long-term benefits of amlodipine-based treatment compared with atenolol-based treatment in reducing CV events appear to be primarily mediated by an effect on systolic BPV during the trial period.


Subject(s)
Atenolol , Hypertension , Humans , Blood Pressure/physiology , Atenolol/therapeutic use , Atenolol/pharmacology , Antihypertensive Agents/therapeutic use , Antihypertensive Agents/pharmacology , Hypertension/complications , Amlodipine/therapeutic use , Risk Factors
4.
Lancet Neurol ; 22(11): 991-1004, 2023 11.
Article in English | MEDLINE | ID: mdl-37863608

ABSTRACT

BACKGROUND: Hypertension is the leading risk factor for cerebral small vessel disease. We aimed to determine whether antihypertensive drug classes differentially affect microvascular function in people with small vessel disease. METHODS: We did a multicentre, open-label, randomised crossover trial with blinded endpoint assessment at five specialist centres in Europe. We included participants aged 18 years or older with symptomatic sporadic small vessel disease or cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) and an indication for antihypertensive treatment. Participants were randomly assigned (1:1:1) to one of three sequences of antihypertensive treatment using a computer-generated multiblock randomisation, stratified by study site and patient group. A 2-week washout period was followed by three 4-week periods of oral monotherapy with amlodipine, losartan, or atenolol at approved doses. The primary endpoint was change in cerebrovascular reactivity (CVR) determined by blood oxygen level-dependent MRI response to hypercapnic challenge in normal-appearing white matter from the end of washout to the end of each treatment period. Efficacy analyses were done by intention-to-treat principles in all randomly assigned participants who had at least one valid assessment for the primary endpoint, and analyses were done separately for participants with sporadic small vessel disease and CADASIL. This trial is registered at ClinicalTrials.gov, NCT03082014, and EudraCT, 2016-002920-10, and is terminated. FINDINGS: Between Feb 22, 2018, and April 28, 2022, 75 participants with sporadic small vessel disease (mean age 64·9 years [SD 9·9]) and 26 with CADASIL (53·1 years [7·0]) were enrolled and randomly assigned to treatment. 79 participants (62 with sporadic small vessel disease and 17 with CADASIL) entered the primary efficacy analysis. Change in CVR did not differ between study drugs in participants with sporadic small vessel disease (mean change in CVR 1·8 × 10-4%/mm Hg [SE 20·1; 95% CI -37·6 to 41·2] for amlodipine; 16·7 × 10-4%/mm Hg [20·0; -22·3 to 55·8] for losartan; -7·1 × 10-4%/mm Hg [19·6; -45·5 to 31·1] for atenolol; poverall=0·39) but did differ in patients with CADASIL (15·7 × 10-4%/mm Hg [SE 27·5; 95% CI -38·3 to 69·7] for amlodipine; 19·4 × 10-4%/mm Hg [27·9; -35·3 to 74·2] for losartan; -23·9 × 10-4%/mm Hg [27·5; -77·7 to 30·0] for atenolol; poverall=0·019). In patients with CADASIL, pairwise comparisons showed that CVR improved with amlodipine compared with atenolol (-39·6 × 10-4%/mm Hg [95% CI -72·5 to -6·6; p=0·019) and with losartan compared with atenolol (-43·3 × 10-4%/mm Hg [-74·3 to -12·3]; p=0·0061). No deaths occurred. Two serious adverse events were recorded, one while taking amlodipine (diarrhoea with dehydration) and one while taking atenolol (fall with fracture), neither of which was related to study drug intake. INTERPRETATION: 4 weeks of treatment with amlodipine, losartan, or atenolol did not differ in their effects on cerebrovascular reactivity in people with sporadic small vessel disease but did result in differential treatment effects in patients with CADASIL. Whether antihypertensive drug classes differentially affect clinical outcomes in people with small vessel diseases requires further research. FUNDING: EU Horizon 2020 programme.


Subject(s)
CADASIL , Hypertension , Humans , Middle Aged , Aged , Antihypertensive Agents/pharmacology , Antihypertensive Agents/therapeutic use , Blood Pressure , Losartan/pharmacology , Losartan/therapeutic use , Atenolol/pharmacology , Atenolol/therapeutic use , CADASIL/drug therapy , Cross-Over Studies , Treatment Outcome , Hypertension/drug therapy , Amlodipine/pharmacology , Amlodipine/therapeutic use , Double-Blind Method
5.
J Vet Cardiol ; 48: 19-30, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37307692

ABSTRACT

INTRODUCTION/OBJECTIVES: Dogs with severe subaortic stenosis (SAS) are at risk of dying suddenly from fatal arrhythmias. Survival is not improved when treated with pure beta-adrenergic receptor (ß)-blockers; however, the effect of other antiarrhythmic drugs on survival is unknown. Sotalol is both a ß-blocker and a class III antiarrhythmic drug; the combination of these differing mechanisms may provide benefit to dogs with severe SAS. The primary objective of this study was to compare survival in dogs with severe SAS that were treated with either sotalol or atenolol. The secondary objective was to evaluate the effect of pressure gradient (PG), age, breed, and aortic regurgitation on survival. ANIMALS: Forty-three client-owned dogs. MATERIALS AND METHODS: Retrospective cohort study. Medical records of dogs diagnosed with severe SAS (PG ≥ 80 mmHg) between 2003 and 2020 were reviewed. RESULTS: No statistical difference was identified in survival time between dogs treated with sotalol (n=14) and those treated with atenolol (n=29) when evaluating all-cause mortality (p=0.172) or cardiac-related mortality (p=0.157). Of the dogs that died suddenly, survival time was significantly shorter in dogs treated with sotalol compared to those treated with atenolol (p=0.046). Multivariable analysis showed that PG (p=0.002) and treatment with sotalol (p=0.050) negatively influenced survival in the dogs that died suddenly. CONCLUSIONS: Sotalol did not have a significant effect on survival overall but may increase the risk of sudden death in dogs with severe SAS compared to atenolol.


Subject(s)
Aortic Stenosis, Subvalvular , Dog Diseases , Dogs , Animals , Sotalol/therapeutic use , Atenolol/therapeutic use , Constriction, Pathologic/veterinary , Retrospective Studies , Anti-Arrhythmia Agents/therapeutic use , Adrenergic beta-Antagonists/therapeutic use , Aortic Stenosis, Subvalvular/veterinary , Dog Diseases/drug therapy
6.
Ann Otol Rhinol Laryngol ; 132(3): 332-340, 2023 Mar.
Article in English | MEDLINE | ID: mdl-35466712

ABSTRACT

BACKGROUND: Although propranolol has been established as the gold standard when treatment is sought for infantile hemangioma, concerns over its side effect profile have led to increasing usage of atenolol, a beta-1 selective blocker. METHODS: A systematic review of PubMed, Scopus, CINAHL, Google Scholar, and Cochrane was conducted following PRISMA guidelines using MeSH terms and keywords for the terms propranolol, atenolol, and infantile hemangioma, including alternative spellings. All randomized control trials (RCTs) or cohort studies directly comparing outcomes of hemangioma treatment with atenolol and propranolol were included. A meta-analysis with pooled mean differences, pooled odds ratios, and analysis of proportions was performed. RESULTS: A total of 669 participants in 7 studies (3 RCTs and 4 cohort) were included. Propranolol showed a significantly higher rate of complete response compared to atenolol (73.3% vs 85.4%, P = .0004). The pooled mean difference of 0.07 (95% CI -0.12, 0.27) in Hemangioma Activity Score (HAS) was not statistically significant. In terms of side effects, there were significantly more agitation and bronchial hyperreactivity events in the propranolol group (P = .0245 and P < .0001, respectively). Overall, there was a significantly greater number of adverse events in the propranolol group compared to the atenolol group (185 vs 117, P < .00001). The overall pooled odds ratio was 2.70 (95% CI 1.90, 3.84), indicating that there is 2.7 times higher odds of adverse events in the propranolol group. CONCLUSION: Propranolol treatment leads to a significantly higher rate of complete response than atenolol. However, its use must be weighed against its greater side effect profile.


Subject(s)
Drug-Related Side Effects and Adverse Reactions , Hemangioma, Capillary , Hemangioma , Humans , Infant , Propranolol/therapeutic use , Atenolol/therapeutic use , Hemangioma, Capillary/drug therapy , Hemangioma, Capillary/chemically induced , Adrenergic beta-Antagonists/therapeutic use , Hemangioma/drug therapy , Treatment Outcome
8.
Pediatr Cardiol ; 44(3): 618-623, 2023 Mar.
Article in English | MEDLINE | ID: mdl-35902413

ABSTRACT

The Pediatric Heart Network (PHN) trial showed similar efficacy of ß-blockers (BB) and angiotensin receptor blockers (ARB) for aortic root dilation in Marfan syndrome, but the impact on prescription practices is unknown. We hypothesized BB and ARB prescriptions would increase after the trial results were published (2014). Prescription data (2007-2016) were obtained from outpatient encounters (IBM Marketscan) for Marfan syndrome patients (6 months-25 years old). Excluding 2014 as a washout period, we analyzed two intervals: 2007-2013 and 2015-2016. Medication categories included BB, ARB, angiotensin converting enzyme inhibitors (ACEI), combination (BB/ARB and/or BB/ACEI), and no drug. Interrupted time-series analysis assessed immediate level change after publication and change in slope for the trend pre- and post-publication. Odds ratios (OR) and 95% confidence intervals from logistic regressions and generalized estimating equation methods accounted for correlation of prescriptions within patients. In 1499 patients (age 14.1 ± 6.1 years, 59% female) seen 2007-2013, BB trended lower [OR 0.91 (0.89, 0.93), p < 0.001] and ARB trended higher [OR 1.12 (1.07, 1.18), p < 0.001], while combination, ACEI, and no drug remained stable. This trend persisted, but was not significant, for BB [OR 0.54 (0.27, 1.08), p = 0.37] and ARB [OR 1.91 (0.55, 6.69), p = 0.31] in 2015-2016. Combination, ACEI, and no drug remained similar. In short term follow-up, changes in prescription practices following publication of the PHN trial were not statistically significant. This may be due to a change seen prior to publication with early adoption of ARBs that was maintained after confirmation of their effectiveness.


Subject(s)
Losartan , Marfan Syndrome , Adolescent , Adult , Child , Female , Humans , Male , Young Adult , Adrenergic beta-Antagonists/therapeutic use , Angiotensin II Type 1 Receptor Blockers/therapeutic use , Angiotensin Receptor Antagonists/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Atenolol/therapeutic use , Losartan/therapeutic use , Marfan Syndrome/drug therapy , Prescriptions
9.
Vascul Pharmacol ; 146: 107110, 2022 10.
Article in English | MEDLINE | ID: mdl-36103993

ABSTRACT

The mechanisms underlying the success of propranolol in the treatment of infantile hemangioma (IH) remain elusive and do not fully explain the rapid regression of hemangiomatous lesions following drug administration. As autophagy is critically implicated in vascular homeostasis, we determined whether ß-blockers trigger the autophagic flux on infantile hemangioma-derived endothelial cells (Hem-ECs) in vitro. MATERIAL AND METHODS: Fresh tissue specimens, surgically removed for therapeutic purpose to seven children affected by proliferative IH, were subjected to enzymatic digestion. Cells were sorted with anti-human CD31 immunolabeled magnetic microbeads. Following phenotypic characterization, expanded Hem-ECs, at P2 to P6, were exposed to different concentrations (50 µM to 150 µM) of propranolol, atenolol or metoprolol alone and in combination with the autophagy inhibitor Bafilomycin A1. Rapamycin, a potent inducer of autophagy, was also used as control. Autophagy was assessed by Lysotracker Red staining, western blot analysis of LC3BII/LC3BI and p62, and morphologically by transmission electron microscopy. RESULTS: Hem-ECs treated with either propranolol, atenolol or metoprolol displayed positive LysoTracker Red staining. Increased LC3BII/LC3BI ratio, as well as p62 modulation, were documented in ß-blockers treated Hem-ECs. Abundant autophagic vacuoles and multilamellar bodies characterized the cytoplasmic ultrastructural features of autophagy in cultured Hem-ECs exposed in vitro to ß-blocking agents. Importantly, similar biochemical and morphologic evidence of autophagy were observed following rapamycin while Bafilomycin A1 significantly prevented the autophagic flux promoted by ß-blockers in Hem-ECs. CONCLUSION: Our data suggest that autophagy may be ascribed among the mechanisms of action of ß-blockers suggesting new mechanistic insights on the potential therapeutic application of this class of drugs in pathologic conditions involving uncontrolled angiogenesis.


Subject(s)
Hemangioma , Propranolol , Adrenergic beta-Antagonists/pharmacology , Amines , Atenolol/pharmacology , Atenolol/therapeutic use , Autophagy , Cell Proliferation , Child , Endothelial Cells , Hemangioma/pathology , Humans , Macrolides , Metoprolol/therapeutic use , Propranolol/pharmacology , Propranolol/therapeutic use , Sirolimus/pharmacology
10.
Mymensingh Med J ; 31(2): 506-511, 2022 Apr.
Article in English | MEDLINE | ID: mdl-35383773

ABSTRACT

Autonomic balance in untreated essential hypertension is altered and antihypertensive drugs may improve autonomic balance. Losartan and atenolol is drug of choice to treat essential hypertension. Power spectral analysis of Heart Rate Variability (HRV) is a tool for detecting autonomic balance. This study aimed to compare the effect of losartan and atenolol on autonomic balance in essential hypertensive patients. This longitudinal study was conducted in the Department of Physiology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh from July 2012 to June 2013. For this study, 120 diagnosed male hypertensive patients without any treatment (age 30-55 years) were selected from the Out Patients Department of Cardiology, BSMMU, Dhaka on their first day of visit. Sixty apparently healthy normotensive male subjects with similar age were also studied as control. Patients were divided into two equal groups. Sixty (60) patients received 50 mg losartan (oral) and 60 patients received 50 mg atenolol (oral) daily. Autonomic balance was assessed by power spectral analysis of HRV and HRV data were recorded by a polyrite D. HRV data of the patients were measured at baseline, after 3 months and 6 months of medication and data of control were recorded at baseline. For statistical analysis ANOVA, independent sample 't' test and paired sample 't' were performed. High frequency normalized units (HF n.u), total power (TP) were significantly lower (p<0.001) and low frequency normalized unit (LF n.u), LF/HF ratio were significantly higher (p<0.001) in all patients before treatment compared to control. In both drug groups HF n.u and total power were found significantly higher (p<0.001) whereas LF n.u and LF/HF ratio were found significantly lower (p<0.001) after 3 months of treatment compared to their baseline values. After 6 months of treatment, data demonstrated significant further increase (p<0.001) in HF n.u and total power compared to their values after 3 months of treatment. Again these values were found significantly higher in atenolol treated patients compared to losartan group at the end of 6 months of treatment. These result concluded that cardiac autonomic nerve functions may be impaired in essential hypertensive patients before treatment which may improve by treatment with both drugs but the effect is more pronounced in atenolol treatment after longer duration.


Subject(s)
Atenolol , Losartan , Adult , Atenolol/pharmacology , Atenolol/therapeutic use , Bangladesh , Heart Rate/physiology , Humans , Longitudinal Studies , Losartan/pharmacology , Losartan/therapeutic use , Male , Middle Aged
11.
J Vet Cardiol ; 41: 199-208, 2022 Jun.
Article in English | MEDLINE | ID: mdl-35430523

ABSTRACT

BACKGROUND: Subaortic stenosis (SAS) is a commonly diagnosed canine congenital cardiac defect, with severe forms of carrying a poor long-term prognosis. To date, an effective treatment strategy has not been developed in veterinary medicine. This study sought to determine if sotalol, a class III antiarrhythmic, may have salient echocardiographic and antiarrhythmic benefits for medical management for dogs affected with severe SAS. METHODS: Ten dogs diagnosed with severe SAS were enrolled in this prospective, double-blinded, crossover study. Dogs underwent physical exam, non-invasive blood pressure measurement, electrocardiography, echocardiography, and 24-h Holter monitoring. Diagnostics were repeated 12-16 days following randomization to oral atenolol (0.5-1 mg/kg) or sotalol (1-2 mg/kg) twice daily. After a medication taper and four-day washout, dogs were crossed-over to the alternate study medication, and the diagnostics were repeated in 12-16 days. Linear and multinomial mixed models were developed to evaluate the effects of treatments on echocardiographic and electrocardiographic variables. RESULTS: Indices of left ventricular systolic function were reduced based on the volumetric assessment when dogs received sotalol compared to atenolol. No difference was noted between groups in left ventricular systolic function based on the linear assessment. No difference was observed in the reduction in left ventricular outflow tract velocity. No significant differences were observed between treatment groups for any variable on 24-h Holter monitor. CONCLUSIONS: Sotalol may be a viable therapy to consider for dogs with severe SAS based on this pilot study. A larger, prospective study is necessary to investigate further.


Subject(s)
Aortic Stenosis, Subvalvular , Dog Diseases , Animals , Anti-Arrhythmia Agents/pharmacology , Anti-Arrhythmia Agents/therapeutic use , Aortic Stenosis, Subvalvular/veterinary , Atenolol/therapeutic use , Constriction, Pathologic/veterinary , Cross-Over Studies , Dog Diseases/diagnostic imaging , Dog Diseases/drug therapy , Dogs , Echocardiography/veterinary , Electrocardiography/veterinary , Pilot Projects , Prospective Studies , Sotalol/pharmacology , Sotalol/therapeutic use
12.
J Vet Intern Med ; 36(3): 877-885, 2022 May.
Article in English | MEDLINE | ID: mdl-35302255

ABSTRACT

BACKGROUND: Beta-blockade is sometimes used in dogs with pulmonic stenosis with the intent of reducing frequency of ventricular arrhythmias during right heart catheterization. OBJECTIVES: To evaluate if pretreatment with atenolol reduces frequency of ventricular arrhythmias, anesthetist interventions, or shortens procedure time. ANIMALS: Thirty dogs with pulmonic stenosis scheduled for interventional procedures. METHODS: Single center, prospective, randomized, open-label study. Dogs were randomized to treatment with atenolol or no treatment preoperatively for a minimum of 10 days. Variables recorded included heart rate, arrhythmias and complexity, total procedure time and administration of antiarrhythmic treatment, vasopressors, positive chronotropes, or fluid boluses. RESULTS: Fifteen dogs were enrolled in each group. Dogs receiving atenolol had lower mean heart rates during the procedure (atenolol 100 ± 11 bpm vs untreated 115 ± 19 bpm, P = .01). There were no significant differences between the atenolol and untreated groups in the frequency of ventricular ectopic complexes (535 [6-5296] vs 553 [79-2863], P = .9), ventricular couplets (46 [0-481] vs 29 [3-121], P = .59), ventricular triplets (20 [0-265] vs 16 [1-82], P = .67), ventricular tachycardia (8 [0-224] vs 8 [1-118], P = .99), proportion exhibiting R-on-T phenomenon (11/15 vs 14/15, P = .33), proportion receiving intraoperative lidocaine (1/15 vs 3/15, P = .6), vasopressors/positive chronotropes (11/15 vs 5/15, P = .06), or fluid boluses (12/15 vs 7/15, P = .13). The procedure time was similar (atenolol 41 [23-68] min vs untreated 35 [18-98] min, P = .91). CONCLUSIONS AND CLINICAL IMPORTANCE: No benefit of preoperative atenolol treatment was identified in this small group of dogs.


Subject(s)
Dog Diseases , Pulmonary Valve Stenosis , Animals , Anti-Arrhythmia Agents/therapeutic use , Arrhythmias, Cardiac/drug therapy , Arrhythmias, Cardiac/veterinary , Atenolol/therapeutic use , Dog Diseases/drug therapy , Dog Diseases/surgery , Dogs , Prospective Studies , Pulmonary Valve Stenosis/veterinary
13.
Epigenetics ; 17(11): 1432-1445, 2022 11.
Article in English | MEDLINE | ID: mdl-35213289

ABSTRACT

Essential hypertension remains the leading risk factor of global disease burden, but its treatment goals are often not met. We investigated whether DNA methylation is associated with antihypertensive responses to a diuretic, a beta-blocker, a calcium channel blocker or an angiotensin receptor antagonist. In addition, since we previously showed an SNP at the transcription start site (TSS) of the catecholamine biosynthesis-related ACY3 gene to associate with blood pressure (BP) response to beta-blockers, we specifically analysed the association of methylation sites close to the ACY3 TSS with BP responses to beta-blockers. We conducted an epigenome-wide association study between leukocyte DNA methylation and BP responses to antihypertensive monotherapies in two hypertensive Finnish cohorts: the GENRES (https://clinicaltrials.gov/ct2/show/NCT03276598; amlodipine 5 mg, bisoprolol 5 mg, hydrochlorothiazide 25 mg, or losartan 50 mg daily) and the LIFE-Fin studies (https://clinicaltrials.gov/ct2/show/NCT00338260; atenolol 50 mg or losartan 50 mg daily). The monotherapy groups consisted of approximately 200 individuals each. We identified 64 methylation sites to suggestively associate (P < 1E-5) with either systolic or diastolic BP responses to a particular study drug in GENRES. These associations did not replicate in LIFE-Fin . Three methylation sites close to the ACY3 TSS were associated with systolic BP responses to bisoprolol in GENRES but not genome-wide significantly (P < 0.05). No robust associations between DNA methylation and BP responses to four different antihypertensive drugs were identified. However, the findings on the methylation sites close to the ACY3 TSS may support the role of ACY3 genetic and epigenetic variation in BP response to bisoprolol.


Subject(s)
Antihypertensive Agents , Hypertension , Humans , Antihypertensive Agents/therapeutic use , Cross-Over Studies , Losartan/therapeutic use , Bisoprolol/therapeutic use , Calcium Channel Blockers/therapeutic use , Atenolol/pharmacology , Atenolol/therapeutic use , DNA Methylation , Hypertension/drug therapy , Hypertension/genetics , Hydrochlorothiazide/therapeutic use , Amlodipine/therapeutic use , Diuretics/therapeutic use , Angiotensin Receptor Antagonists/therapeutic use , Double-Blind Method , Catecholamines/therapeutic use , Treatment Outcome
15.
Pak J Pharm Sci ; 34(5(Supplementary)): 1891-1895, 2021 Sep.
Article in English | MEDLINE | ID: mdl-34836856

ABSTRACT

Blood pressure control in hypertensive patients with metabolic abnormalities is challenging because many antihypertensive drugs adversely affect metabolism. Nebivolol a 3rd generation vasodilatory ß-blocker offer neutral or beneficial effects on insulin sensitivity and lipid metabolism. The purpose of this study was to evaluate the effect of nebivolol and atenolol on glycemic control and lipid profile in type 2 diabetes patients with concomitant hypertension. We conducted a 12 weeks double blind randomized clinical trial at Sheik Zayed Hospital Rahim Yar Khan. Patients were randomly divided in to two groups. Patients in group were given tablet nebivolol 5-10mg while patients in group B were given tablet Atenolol 25-50mg/daily for a period of 12 weeks. Pre and post data were analyzed by SPSS 20. After 12 weeks, Both drugs lowered blood pressure significantly i.e. nebivolol (SBP from152±12 to130±14 with p=0.004, DBP from 95±12 to78±8.5 with p=0.002) Atenolol (SBP from148±16.5 to 128±15.5 with p=0.006, DBP from 90±10.5 to 82±12 with p=0.003).Similarly both Nebivolol and Atenolol did not any significant effect on glycemic control and lipid profile at 12 week with in groups. However when comparison was done between two groups, Nebivolol significantly reduced blood sugar (p=0.001), HbA1c (p=0.0032), total Cholesterol (p=0.002), triglycerides (p=0.012), LDL-Cholesterol (p=0.007) and HDL-Cholesterol (p=0.001) as compared to atenolol. In comparison with atenolol, Nebivolol has a beneficial effect on glycemic control and serum lipid profile.


Subject(s)
Atenolol/therapeutic use , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/drug therapy , Glycemic Control , Hypertension/drug therapy , Hypertension/etiology , Hypolipidemic Agents/pharmacology , Lipid Metabolism/drug effects , Nebivolol/pharmacology , Adult , Blood Glucose/analysis , Blood Pressure/drug effects , Cholesterol/blood , Diabetes Mellitus, Type 2/blood , Double-Blind Method , Female , Glycated Hemoglobin , Humans , Hypertension/blood , Male , Middle Aged , Triglycerides/blood , Young Adult
16.
Naunyn Schmiedebergs Arch Pharmacol ; 394(10): 2117-2128, 2021 10.
Article in English | MEDLINE | ID: mdl-34398250

ABSTRACT

The incidence of chronic kidney disease is escalating; cardiorenal syndrome (CRS) type 4 is gaining a major health concern causing significant morbidity and mortality, putting major burdens on the healthcare system. This study was designed to compare the cardioprotective effects of carvedilol versus atenolol against CRS type 4 induced by subtotal 5/6 nephrectomy in rats and to explore the underlying mechanisms. Immediately after surgery, carvedilol (20 mg/kg/day) or atenolol (20 mg/kg/day) was added to drinking water for 10 weeks. Carvedilol was more effective than atenolol in improving kidney functions, decreasing elevated blood pressures, attenuating cardiac hypertrophy, reducing serum brain natriuretic peptide, and diminished cardiac fibrous tissue deposition. However, carvedilol was equivalent to atenolol in modulating ß1-adrenergic receptors (ß1ARs) and cardiac diacylglycerol (DAG) signaling, but carvedilol was superior in modulating ß-arrestin2, phosphatidyl inositol 4,5 bisphosphates (PIP2), and caspase 3 levels. Carvedilol has superior cardioprotective effects than atenolol in a rat model of CRS type 4. These protective effects are mediated through modulating cardiac ß1ARs/ß-arrestin2/PIP2/DAG as well as abating cardiac apoptotic signaling pathways (caspase3/pS473 protein kinase B (Akt)).


Subject(s)
Atenolol/therapeutic use , Cardio-Renal Syndrome/drug therapy , Cardiomegaly/drug therapy , Cardiotonic Agents/therapeutic use , Carvedilol/therapeutic use , Animals , Apoptosis/drug effects , Atenolol/pharmacology , Blood Pressure/drug effects , Cardio-Renal Syndrome/metabolism , Cardio-Renal Syndrome/physiopathology , Cardio-Renal Syndrome/surgery , Cardiomegaly/metabolism , Cardiomegaly/physiopathology , Cardiomegaly/surgery , Cardiotonic Agents/pharmacology , Carvedilol/pharmacology , Diacylglycerol Kinase/metabolism , Disease Models, Animal , Kidney/drug effects , Kidney/physiology , Male , Myocardium/metabolism , Nephrectomy , Phosphatidylinositol 4,5-Diphosphate/metabolism , Rats, Wistar , Receptors, Adrenergic, beta-1/metabolism , beta-Arrestin 2/metabolism
17.
Stroke ; 52(10): 3088-3096, 2021 10.
Article in English | MEDLINE | ID: mdl-34192893

ABSTRACT

Background and Purpose: Management of stroke risk factors might reduce later dementia. In ASCOT (Anglo-Scandinavian Outcome Trial), we determined whether dementia or stroke were associated with different blood pressure (BP)­lowering regimens; atorvastatin or placebo; and mean BP, BP variability, and mean cholesterol levels. Methods: Participants with hypertension and ≥3 cardiovascular disease risk factors were randomly allocated to amlodipine- or atenolol-based BP-lowering regimen targeting BP <140/90 mm Hg for 5.5 years. Participants with total cholesterol ≤6.5 mmol/L were also randomly allocated to atorvastatin 10 mg or placebo for 3.3 years. Mean and LDL (low-density lipoprotein) cholesterol, BP, and SD of BP were calculated from 6 months to end of trial. UK participants were linked to electronic health records to ascertain deaths and hospitalization in general and mental health hospitals. Dementia and stroke were ascertained by validated code lists and within-trial ascertainment. Results: Of 8580 UK participants, 7300 were followed up to 21 years from randomization. Atorvastatin for 3.3 years had no measurable effect on stroke (264 versus 272; adjusted hazard ratio [HR], 0.92 [95% CI, 0.78­1.09]; P=0.341) or dementia (238 versus 227; adjusted HR, 0.98 [95% CI, 0.82­1.18]; P=0.837) compared with placebo. Mean total cholesterol was not associated with later stroke or dementia. An amlodipine-based compared with an atenolol-based regimen for 5.5 years reduced stroke (443 versus 522; adjusted HR, 0.82 [95% CI, 0.72­0.93]; P=0.003) but not dementia (450 versus 465; adjusted HR, 0.94 [95% CI, 0.82­1.07]; P=0.334) over follow-up. BP variability (SD mean BP) was associated with a higher risk of dementia (per 5 mm Hg HR, 1.14 [95% CI, 1.06­1.24]; P<0.001) and stroke (HR, 1.21 [95% CI, 1.12­1.32]; P<0.001) adjusted for mean BP. Conclusions: An amlodipine-based BP regimen reduced the long-term incidence of stroke compared with an atenolol-based regimen but had no measurable effect on dementia. Atorvastatin had no effect on either stroke or dementia. Higher BP variability was associated with a higher incidence of later dementia and stroke.


Subject(s)
Antihypertensive Agents/therapeutic use , Dementia/epidemiology , Stroke/epidemiology , Aged , Amlodipine/therapeutic use , Anticholesteremic Agents/therapeutic use , Atenolol/therapeutic use , Atorvastatin/therapeutic use , Cholesterol/blood , Female , Humans , Hypertension/drug therapy , Incidence , Male , Middle Aged , Risk Factors , Scandinavian and Nordic Countries/epidemiology , Treatment Outcome , United Kingdom/epidemiology
18.
J Am Soc Nephrol ; 32(6): 1454-1463, 2021 06 01.
Article in English | MEDLINE | ID: mdl-33958490

ABSTRACT

BACKGROUND: The implications of removing the adjustment for Black race in equations to eGFR on the prevalence of CKD and management strategies are incompletely understood. METHODS: We estimated changes in CKD prevalence and the potential effect on therapeutic drug prescriptions and prediction of kidney failure if race adjustment were removed from the CKD-EPI GFR estimating equation. We used cross-sectional and longitudinal data from adults aged ≥18 years in the National Health and Nutrition Examination Survey (NHANES) from 2015 to 2016, and the Veterans Affairs (VA) Health Care System in 2015. In the VA cohort, we assessed use of common medications that require dose adjustment on the basis of kidney function, and compared the prognostic accuracy of the Kidney Failure Risk Equation with versus without race adjustment of eGFR. RESULTS: The prevalence of CKD among Black adults increased from 5.2% to 10.6% in NHANES, and from 12.4% to 21.6% in the VA cohort after eliminating race adjustment. Among Black veterans, 41.0% of gabapentin users, 33.5% of ciprofloxacin users, 24.0% of metformin users, 6.9% of atenolol users, 6.6% of rosuvastatin users, and 5.8% of tramadol users were reclassified to a lower eGFR for which dose adjustment or discontinuation is recommended. Without race adjustment of eGFR, discrimination of the Kidney Failure Risk Equation among Black adults remained high and calibration was marginally improved overall, with better calibration at higher levels of predicted risk. CONCLUSIONS: Removal of race adjustment from CKD-EPI eGFR would double the estimated prevalence of CKD among Black adults in the United States. Such a change is likely to affect a sizeable number of drug-dosing decisions. It may also improve the accuracy of kidney failure risk prediction among higher-risk Black adults.


Subject(s)
Black or African American/statistics & numerical data , Glomerular Filtration Rate , Mathematical Concepts , Renal Insufficiency, Chronic/classification , Renal Insufficiency, Chronic/ethnology , Veterans/statistics & numerical data , Adrenergic beta-1 Receptor Antagonists/therapeutic use , Adult , Aged , Aged, 80 and over , Analgesics, Opioid/therapeutic use , Anti-Bacterial Agents , Anticonvulsants/therapeutic use , Atenolol/therapeutic use , Ciprofloxacin/therapeutic use , Female , Gabapentin/therapeutic use , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Hypoglycemic Agents , Male , Metformin/therapeutic use , Middle Aged , Nutrition Surveys , Prevalence , Prognosis , Race Factors , Renal Insufficiency, Chronic/physiopathology , Risk Factors , Rosuvastatin Calcium/therapeutic use , Tramadol/therapeutic use , United States/epidemiology , Young Adult
19.
JAMA Otolaryngol Head Neck Surg ; 147(7): 599-607, 2021 07 01.
Article in English | MEDLINE | ID: mdl-33856430

ABSTRACT

Importance: Propranolol has become the first-line therapy for problematic infantile hemangiomas (IHs) that require systemic therapy. However, different adverse events have been reported during propranolol treatment. The positive efficacy and safety of atenolol raise the question of whether it could be used as a promising therapy for IH. Objective: To compare the efficacy and safety of propranolol vs atenolol in infants (between age 5 and 20 weeks) with problematic IHs who required systemic therapy. Design, Setting, and Participants: This was a prospective, multicenter, randomized, controlled, open-label clinical trial conducted in collaboration among 6 separate investigation sites in China from February 1, 2015, to December 31, 2018. A total of 377 patients met the criteria for inclusion and were randomized to the propranolol (190 [50.4%]) and atenolol (187 [49.6%]) groups. Data were analyzed in June 2020. Interventions: Participants were randomized to receive either propranolol or atenolol for at least 6 months. They completed efficacy assessments at 2 years after the initial treatment. Main Outcomes and Measures: The primary outcome was any response or nonresponse at 6 months. The key secondary outcome was changes in the hemangioma activity score. Results: Of 377 participants, 287 (76.1%) were female, and the mean (SD) age was 10.2 (4.0) weeks in the propranolol group and 9.8 (4.1) weeks in the atenolol group. After 6 months of treatment, in the propranolol and atenolol groups, the overall response rates were 93.7% and 92.5%, respectively (difference, 1.2%; 95% CI, -4.1% to 6.6%). At 1 and 4 weeks after treatment, and thereafter, the hemangioma activity score in the atenolol group aligned with the propranolol group (odds ratio, 1.034; 95% CI, 0.886-1.206). No differences between the propranolol group and atenolol group were observed in successful initial responses, quality of life scores, complete ulceration healing times, or the rebound rate. Both groups presented a similar percentage of complete/nearly complete responses at 2 years (82.1% vs 79.7%; difference, 2.4%; 95% CI, -5.9% to 10.7%). Adverse events were more common in the propranolol group (70.0% vs 44.4%; difference, 25.6%; 95% CI, 15.7%-34.8%), but the frequency of severe adverse events did not differ meaningfully between the groups. Conclusions and Relevance: In this randomized clinical trial, when compared with propranolol, atenolol had similar efficacy and fewer adverse events in the treatment of infants with problematic IHs. The results suggest that oral atenolol can be used as an alternative treatment option for patients with IH who require systemic therapy. Trial Registration: ClinicalTrial.gov Identifier: NCT02342275.


Subject(s)
Adrenergic beta-1 Receptor Antagonists/therapeutic use , Adrenergic beta-Antagonists/therapeutic use , Atenolol/therapeutic use , Hemangioma, Capillary/drug therapy , Propranolol/therapeutic use , Adrenergic beta-1 Receptor Antagonists/administration & dosage , Adrenergic beta-Antagonists/administration & dosage , Atenolol/administration & dosage , China , Female , Humans , Infant , Male , Propranolol/administration & dosage , Prospective Studies
20.
JAMA Netw Open ; 4(4): e218418, 2021 04 01.
Article in English | MEDLINE | ID: mdl-33914047

ABSTRACT

Importance: Accumulating evidence indicates that higher blood pressure (BP) variability from one physician office visit to the next (hereafter referred to as visit-to-visit BP variability) is associated with poor outcomes. Short-term measurement (throughout 1 year) of visit-to-visit BP variability in high-risk older patients may help identify patients at increased risk of death. Objective: To evaluate whether short-term visit-to-visit BP variability is associated with increased long-term mortality risk. Design, Setting, and Participants: The US cohort of the International Verapamil SR-Trandolapril Study (INVEST), a randomized clinical trial of 16 688 patients aged 50 years or older with hypertension and coronary artery disease, was conducted between September 2, 1997, and December 15, 2000, with in-trial follow-up through February 14, 2003. The study evaluated a calcium antagonist (sustained-release verapamil plus trandolapril) vs ß-blocker (atenolol plus hydrochlorothiazide) treatment strategy. Blood pressure measurement visits were scheduled every 6 weeks for the first 6 months and biannually thereafter. Statistical analysis was performed from September 2, 1997, to May 1, 2014. Exposures: Visit-to-visit systolic BP (SBP) and diastolic BP variability during the first year of enrollment using 4 different BP variability measures: standard deviation, coefficient of variation, average real variability, and variability independent of the mean. Main Outcomes and Measures: All-cause death, assessed via the US National Death Index, beginning after the exposure assessment period through May 1, 2014. Results: For the present post hoc analysis, long-term mortality data were available on 16 688 patients (9001 women [54%]; mean [SD] age, 66.5 [9.9] years; 45% White patients, 16% Black patients, and 37% Hispanic patients). During a mean (SD) follow-up of 10.9 (4.2) years, 5058 patients (30%) died. All 4 variability measures for SBP were significantly associated with long-term mortality after adjustment for baseline demographic characteristics and comorbidities. After comparison of lowest vs highest variability measure quintiles, the magnitude of the association with death remained statistically significant even after adjustment for baseline demographic characteristics and comorbidities (average real variability: adjusted hazard ratio [aHR], 1.18; 95% CI, 1.08-1.30; standard deviation: aHR, 1.14; 95% CI, 1.04-1.24; coefficient of variation: aHR, 1.15; 95% CI, 1.06-1.26; variability independent of the mean: aHR, 1.15; 95% CI, 1.05-1.25). The signal was stronger in women compared with men. Associations of diastolic BP variability measures with death were weaker than for SBP and were not significant after adjustment. Conclusions and Relevance: This study suggests that, in a large population of older patients with hypertension and coronary artery disease, short-term visit-to-visit SBP variability was associated with excess long-term mortality, especially for women. Efforts to identify and minimize visit-to-visit SBP variability may be important in reducing excess mortality later in life. Trial Registration: ClinicalTrials.gov Identifier: NCT00133692.


Subject(s)
Coronary Artery Disease/complications , Hypertension/physiopathology , Mortality , Aged , Antihypertensive Agents/therapeutic use , Atenolol/therapeutic use , Blood Pressure , Female , Humans , Hydrochlorothiazide/therapeutic use , Hypertension/complications , Hypertension/drug therapy , Indoles/therapeutic use , Kaplan-Meier Estimate , Male , Middle Aged , Proportional Hazards Models , Randomized Controlled Trials as Topic , Sex Factors , Verapamil/therapeutic use
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