Time course for blood pressure lowering of beta-blockers with partial agonist activity.

BACKGROUND: Beta-blockers are commonly used in the treatment of hypertension. We do not know whether the blood pressure (BP) lowering efficacy of beta-blockers varies across the day. This review focuses on the subclass of beta-blockers with partial agonist activity (BBPAA). OBJECTIVES: To assess the degree of variation in hourly BP lowering efficacy of BBPAA over a 24-hour period in adults with essential hypertension. SEARCH METHODS: The Cochrane Hypertension Information Specialist searched the following databases for relevant studies up to June 2020: the Cochrane Hypertension Specialised Register; CENTRAL; 2020, Issue 5; MEDLINE Ovid; Embase Ovid; the World Health Organization International Clinical Trials Registry Platform; and ClinicalTrials.gov. We also contacted authors of relevant papers regarding further published and unpublished work. The searches had no language restrictions. SELECTION CRITERIA: We sought to include all randomised and non-randomised trials that assessed the hourly effect of BBPAA by ambulatory monitoring, with a minimum follow-up of three weeks. DATA COLLECTION AND ANALYSIS: Two review authors independently selected the included trials and extracted the data. We assessed the certainty of the evidence using the GRADE approach. Outcomes included in the review were end-point hourly systolic and diastolic blood pressure (SBP and DBP) and heart rate (HR), measured using a 24-hour ambulatory BP monitoring (ABPM) device. MAIN RESULTS: Fourteen non-randomised baseline controlled trials of BBPAA met our inclusion criteria, but only seven studies, involving 121 participants, reported hourly ambulatory BP data that could be included in the meta-analysis. Beta-blockers studied included acebutalol, pindolol and bopindolol. We judged most studies at high or unclear risk of bias for selection bias, attrition bias, and reporting bias. We judged the overall certainty of the evidence to be very low for all outcomes. We analysed and presented data by each hour post-dose. Very low-certainty evidence showed that hourly mean reduction in BP and HR visually showed an attenuation over time. Over the 24-hour period, the magnitude of SBP lowering at each hour ranged from -3.68 mmHg to -17.74 mmHg (7 studies, 121 participants), DBP lowering at each hour ranged from -2.27 mmHg to -9.34 mmHg (7 studies, 121 participants), and HR lowering at each hour ranged from -0.29 beats/min to -10.29 beats/min (4 studies, 71 participants). When comparing between three 8-hourly time intervals that correspond to day, evening, and night time hours, BBPAA was less effective at lowering BP and HR at night, than during the day and evening. However, because we judged that these outcomes were supported by very low-certainty evidence, further research is likely to have an important impact on the estimate of effect and may change the conclusion. AUTHORS' CONCLUSIONS: There is insufficient evidence to draw general conclusions about the degree of variation in hourly BP-lowering efficacy of BBPAA over a 24-hour period, in adults with essential hypertension. Very low-certainty evidence showed that BBPAA acebutalol, pindolol, and bopindolol lowered BP more during the day and evening than at night. However, the number of studies and participants included in this review was very small, further limiting the certainty of the evidence. We need further and larger trials, with accurate recording of time of drug intake, and with reporting of standard deviation of BP and HR at each hour.

First Case Report of Smith-Magenis Syndrome (SMS) Among the Arab Community in Nazareth: View and Overview.

Smith-Magenis syndrome (SMS0) is a complex and rare genetic multisystem disorder characterized by a variable pattern of cognitive deficits accompanied by a1 distinctive behavioral phenotype. SMS is characterized by subtle facial dysmorphology, short stature, sleep disturbances, and neurobehavioral abnormalities. Little is known about the manifestation of his unique case among Arab population and its strategic treatment.This study comes to present a case of SMS in an Arab newborn male who was born in spontaneous delivery on June 29, 2015, with tachypnea, tracheomalacia, and mild hypotonia. The newborn was admitted on the Neonatal Intensive Care Unit (NICU), and various laboratory examinations and clinical examinations were performed.Throughout his hospitalization, feeding difficulties appeared and thus a peripheral venous catheter was inserted in the left leg.After 22 days of follow-up and hospitalizations, the patient status improved and he was discharged with recommendations to be in follow up in pediatric outpatient clinic.However, notwithstanding the different investigations, intermittent tachypnea continued at a rate of 72 to 77 breaths/min. Search for diagnosis begin intensively owing to persistence of tachypnia, mild hypotonia, feeding difficulties, sleep disturbances, and mild dysmorphic facial features. Suspicions of genetic abnormalities were considered and blood samples were sent for chromosome analysis and for fluorescent in situ hybridization (FISH) testing.The genetic results revealed the following: cytogenetic findings: 46, XY, del(17)(p11.2) and the FISH results: del(17)(p11.2p11.2) (D17S29). The chromosome diagnosis revealed an interstitial deletion of 17p11.2 and the diagnosis of the SMS was confirmed.Accurate clinical diagnosis, therapeutic assessments and a holistic management plans, including multidiscipline therapeutic strategies, periodic neuro-developmental assessments, and an early intervention programs, are recommended.However, cytogenetic analysis or FISH using an RAI1-specific probe is the most frequently used technique for DS. Sleep and behavioral disturbances treatment include a combination of the daytime dose of acebutolol with an evening oral dose of melatonin. Melatonin as chronobiotic, antioxidant, and analgesic agent showed to be effective in different primary sleep disorders and in those associated with neurobehavioral disorders. Based on the beneficial effect of melatonin, it will be useful to use serum levels of melatonin as a follow-up test.

Comparative efficacy and usefulness of acebutolol and diltiazem for the prevention of atrial fibrillation during perioperative time in patients undergoing pulmonary resection.

BACKGROUND: Postthoracic surgery atrial fibrillation (AF) is the most frequently occurring arrhythmia. Strategies for preventing AF have been amply evaluated, but currently there are no clearly defined guidelines for treatment of AF after thoracic surgery. METHODS: The study was prospective and randomized controlled trial. Acebutolol and diltiazem versus placebo were compared, among 117 patients postpneumonectomy or lobectomy at the Thoracosurgery Clinic, Poznan University of Medical Sciences in Poland. Patients who were enrolled in the study were randomly assigned to one of the three groups: those who received acebutolol (Group 1) or diltiazem (Group 2) and compared with patients without antiarrhythmic drugs (Group 0). Each group consisted of 39 patients. The patients were continuously monitored postoperatively with 24 ECG (Holter monitor) in the intensive care unit. RESULTS: In patients receiving acebutolol AF occurred in 5% compared with 23% of patients receiving diltiazem and 20% of patients receiving placebo (difference not statistically significant). CONCLUSIONS: Acebutolol and diltiazem appear to have been non-effective for the treatment or prevention of AF. Side effects were mild. In comparison to diltiazem, however, acebutolol had a beneficial effect on the circulatory system. Patients who had received acebutolol proved to have had fewer tachycardia episodes and supraventricular ectopy during the postoperative period. It seems that acebutolol can be useful, especially in patients with sympathetic activity dominance.

Follow-up with exercise test of effort-induced ventricular arrhythmias linked to ryanodine receptor type 2 gene mutations.

The aim of this study was to assess exercise test results and efficacy of therapy with a ß blocker (acebutolol) in ryanodine receptor type 2 (RyR2) mutation carriers with documented ventricular arrhythmias (VAs) and long-term follow-up. Twenty RyR2 mutation carriers belonging to 8 families and regularly followed at our center were analyzed using a study protocol involving electrocardiography, exercise tests off and on ß-blocker therapy, 2-dimensional echocardiography, and signal-averaged electrocardiography. Off-therapy exercise testing triggered the onset of VAs at different heart rates (mean 132 ± 13 beats/min) with various patterns that worsened while exercising and disappeared immediately after stopping. The most severe VAs detected were nonsustained ventricular tachycardia in 35% and ventricular couplets in 35%. In the remaining subjects single ventricular premature beats were recorded. In 15% of patients single monomorphic ventricular premature beats were detected and identified to be linked to RyR2 mutations owing to the presence of sudden deaths of their family members and subsequent family screening. Acebutolol made the VAs disappear completely in 20% of subjects and decreased their complexity in 50%, whereas it did not change VAs appreciably in 30% of patients with less complex VAs. After 11 ± 8 years of follow-up 2 patients developed syncope. In conclusion, exercise testing was a fundamental tool for assessing the clinical phenotype and efficacy of therapy in RyR2 mutation carriers and therapy with acebutolol led in most subjects to a decreased complexity of the arrhythmic pattern or to complete suppression.

Infantile haemangioma and ß-blockers in otolaryngology.

Infantile haemangioma (IH) is the most common tumour during early childhood. Although these benign lesions resolve spontaneously, up until recently laryngotracheal sites of IH required invasive management. The dramatic efficacy of ß-blockers on IH has radically changed the prognosis. Surgery is now no longer indicated as first-line therapy, but should only be performed for difficult, refractory cases, or in the presence of absolute contraindications to ß-blockers. Long-term steroid therapy is also no longer indicated. Propranolol can be used as first-line, single-agent therapy.

A population-based analysis of the class effect of beta-blockers after myocardial infarction.

BACKGROUND: Long-term treatment with beta-blockers reduces mortality after acute myocardial infarction (AMI). Whether beta-blockers exert a class effect is unknown. METHODS: We analyzed mortality after AMI in Canadian patients 65 years or older who were discharged from hospital with a diagnosis of AMI from April 1996 to March 2000. Administrative data from Quebec, Ontario, and British Columbia were merged. We compared patients prescribed with metoprolol, acebutolol, or atenolol within 90 days after discharge. RESULTS: Among 31576 patients, 67% were prescribed with metoprolol, 24% with atenolol, and 9% with acebutolol. Clinical characteristics and proportion of days covered with a beta-blocker prescription were similar across groups. Although controlling for time-dependent covariates representing current use and dosage, as well as for age, sex, congestive heart failure, and several other comorbidities, patients who filled a prescription for acebutolol (hazard ratio 0.71, 95% CI 0.62-0.81) or atenolol (hazard ratio 0.79, 95% CI 0.73-0.87) had significantly lower mortality in comparison with metoprolol. CONCLUSIONS: The higher mortality observed in patients receiving metoprolol compared with those receiving atenolol or acebutolol challenges the concept of a class effect of beta-blockers for secondary prevention of AMI.

[Interrelationship between changes of rate and variability of cardiac rhythm under influence of beta-adrenoblockers].

BACKGROUND: Beta-blocking agents (BB) decrease mortality particularly sudden in post-myocardial infarction patients and in patients with chronic heart failure that is closely related to heart rate (HR) lowering at rest. The hypothesis exists that BB decrease mortality due to increase of cardiac vagal activity. AIM: To evaluate the relation between HR changes on therapy with BB and changes in heart rate variability (HRV). MATERIAL AND METHODS: Sixty patients with arterial hypertension randomized in three groups were studied before and after treatment with atenolol (AT), acebutolol (AC) or talinolol (TL) until doses of 100, 600 and 300 mg/d correspondingly were reached or resting HR was decreased by 10 bpm. 24-hour Holter monitoring was used to measure HR and HRV indexes. RESULTS: Arterial blood pressure decreased significantly in every group. HR max, min and average decreased significantly on AT. AC and TL lowered HR max and AT average but did not change HR min. AT did not change SDNN, SDANN, TotP and ULFP, but AC and NL decreased them significantly (p < 0.001). AT increased SDNNind, VLFP (p < 0.002), rMSSD, pNNSO and HFP (p < 0.003), but did not change LFP. AC and TL did not change these indexes. Changes of HRV indexes were closely related to changes of HR particularly HR min (r=0.53 - 0.84). Linear regressions of these relations did not differ between three drugs except for low frequency indexes of HRV between AC and TL. According to the equations the differences in HRV indexes between the drugs were well explained by the differences in HR changes. When all patients were evaluated together statistical significance of increase in rMSSD, pNN50 and HFP was not reached until HR average decreased by 10 bpm or more. The effect of TL on HR and HRV is very similar to AC what suggests its intrinsic sympathomimetic activity or anticholinergic properties.

Arrhythmogenic right ventricular dysplasia in pregnancy: a case report.

BACKGROUND: Arrhythmogenic right ventricular dysplasia (ARVD) is characterized by progressive fibrous or fibrofatty tissue replacement of the right ventricular myocardium. Interspersed adipocytes and fibrous tissue may provide foci for arrhythmias. The clinical spectrum of ARVD may include asymptomatic premature ventricular complexes to ventricular tachycardia and sudden death. There is currently little information about ARVD in pregnancy. CASE: A 29-year-old primigravida, diagnosed with ARVD 1 year prior to pregnancy, underwent a full-term, uncomplicated pregnancy and delivery while maintained on acebutolol and an implanted cardioverter defibrillator. Her infant was born without an apparent cardiac anomaly or heart rate abnormality. CONCLUSION: Successful management of pregnancy complicated by ARVD can be accomplished with an implanted cardioverter defibrillator and an antiarrhythmic agent. Such patients should be managed with close monitoring during pregnancy for signs and symptoms of arrhythmia and preventive obstetric care appropriate to their clinical profile to optimize normal deliveries.

Changes in serum lipids and antioxidant status in west Algerian patients with essential hypertension treated with acebutolol compared to healthy subjects.

BACKGROUND: Hypertension is a major health problem in both developed and developing countries. It is hypothesized that high blood pressure is associated with loss of balance between peroxidation and antioxidant factors. MATERIAL/METHODS: 40 patients with essential hypertension were studied to ascertain the effects of a selective b1-blocker (acebutolol, 400 mg/day) on serum lipids, antioxidant status, antioxidant enzyme activity in red blood cells (RBC), and membrane fatty acids composition. Each subject was screened by physical examination, ECG, echocardiography, and laboratory tests. The period of observation was 24 weeks, and the data were tested by 2-way ANOVA followed by Bartlett's least significant difference test. RESULTS: At 12 weeks, serum triacylglycerol was more elevated (+26%). At 24 weeks, apolipoprotein A-1 levels remained more elevated (+41%) in hypertensive subjects compared to controls. In hypertensive patients, total antioxidant status and total plasma antioxidant capability were lower at 12 weeks than controls, and increased after 24 weeks of treatment. At 12 weeks, superoxide dismutase, catalase and glutathione reductase activities in erythrocytes remained lower in hypertensive subjects compared to controls (-32%, -40% and -24%, respectively). At 24 weeks, these values were increased compared to those obtained at 12 weeks (+26%, +36% and +37%, respectively). At 12 and 24-weeks, total n-3 and n-6 fatty acids were decreased by 26%, 18% and 29%, 25%, respectively. CONCLUSIONS: These findings demonstrate the beneficial influence of a beta1-blocker (acebutolol) at 24 weeks by its action on serum lipids, antioxidant status and RBC antioxidant enzyme activities.

Beta-adrenergic blockade during severe ischemia.

OBJECTIVE: To examine the effect of acebutolol, a beta-adrenergic-receptor blocker, on severe regional myocardial ischemia, specifically the effects on regional myocardial function and metabolism. DESIGN: Randomized study. SETTING: Animal laboratory of the Department of Anesthesiology and Critical Care, University of Stellenbosch Medical School. PARTICIPANTS: Anesthetized open-chest pig model (n = 18). INTERVENTIONS: Regional left ventricular function and metabolism were evaluated. Severe stenosis was applied to the left anterior descending coronary artery. After establishing regional myocardial ischemia, acebutolol was administered intravenously, and results were compared with controls who did not receive acebutolol. Animals were prospectively randomized to 1 of the groups. MEASUREMENTS AND MAIN RESULTS: Regional myocardial function and metabolism were assessed by end-systolic pressure relationship, regional systolic shortening, postsystolic shortening, regional myocardial oxygen consumption, and lactate dynamics. Coronary blood flow was determined with a Doppler flow probe. Results indicated that acebutolol increased regional myocardial blood flow, and this resulted in less severe regional myocardial ischemia, improved function, and an increase in regional myocardial oxygen consumption. CONCLUSION: The beta-Adrenergic-receptor antagonist was successful in reducing regional myocardial ischemia in this model. This reduction was achieved by an increase in coronary blood flow, which resulted in an improvement in regional mechanical function and an increase in oxygen consumption.

[Acebutolol in the treatment of arterial hypertension in pregnancy--comparison with commonly used hypertensive agents]. / Acebutolol v liecbe artériovej hypertenzie v gravidite--porovnanie s bezne uzívanými antihypertenzívami.

OBJECTIVE: The main purpose of our study was to analyse efficacy and safety of acebutolol (Sectral) in the treatment of hypertension in pregnancy. DESIGN: Cohort clinical study comparing efficacy and safety of acebutolol with other antihypertensive drugs by 77 patients and their 81 newborns. The number of 48 patients were treated by acebutolol. SETTING: Internal Medicine and Clinical Pharmacology Department, Regional Hospital, Nitra and The Faculty of Health Service and Social Work, University of Trnava; Department of Gynaecology and Obstetrics, Regional Hospital Nitra and The Faculty of Health Service and Social Work, University of Trnava; Institute of Pharmacology, The Faculty of Medicine, Komenského University, Bratislava; Environment, a.s. Nitra. METHODS: During the period of 6 years our patients were divided into subgroups according to the type of hypertension in pregnancy and the severity of the illness which was the basis for used antihypertensive drugs. One of the topics of the study was to provide monitoring of adverse events by mother and possible drug influence on their new-born has been evaluated by investigating the week of birth, weight and length of the new-born and evaluating of Apgar score. RESULTS: In the subgroup of 48 women treated by acebutolol we have confirmed the efficacy and safety of this antihypertensive drug without any clinically significant effect on the quality of life of their new-born and evaluating of Apgar score. CONCLUSION: With regard to the results of our clinical study we can consider acebutolol to be effective and safe antihypertensive drug in the treatment of hypertension in pregnancy.

Cardioselective beta-blockers for reversible airway disease.

BACKGROUND: Beta-blocker therapy has mortality benefit in patients with hypertension, heart failure and coronary artery disease, as well as during the perioperative period. These drugs have traditionally been considered contraindicated in patients with reversible airway disease. OBJECTIVES: To assess the effect of cardioselective beta1-blockers on respiratory function of patients with reversible airway disease. Reversible airway disease was defined as asthma or chronic obstructive pulmonary disease with a reversible obstructive component. SEARCH STRATEGY: A comprehensive search of EMBASE, MEDLINE and CINAHL was performed using the Cochrane Airways Group registry to identify randomized blinded placebo-controlled trials from 1966 to May 2001. The search was completed using the terms: asthma*, bronchial hyperreactivity*, respiratory sounds*, wheez*, obstructive lung disease* or obstructive airway disease*, and adrenergic antagonist*, sympatholytic* or adrenergic receptor block*. We did not exclude trials on the basis of language. SELECTION CRITERIA: Randomized, blinded, placebo-controlled trials of single dose or longer duration that studied the effects of cardioselective beta1-blockers on the forced expiratory volume in 1 second (FEV1), symptoms and use of short-acting inhaled beta2-agonists, in patients with reversible airway disease. Reversible airway disease was documented by response to methacholine challenge, by an increase in FEV1 of at least 15% to beta2-agonist administration, or the presence of asthma as defined by the American Thoracic Society. DATA COLLECTION AND ANALYSIS: Two independent reviewers extracted data from the selected articles, reconciling differences by consensus. Cardioselective beta1-blockers were divided into 2 groups, those with or without intrinsic sympathomimetic activity (ISA). Two interventions studied were the administration of beta1-blocker, given either as a single dose or for longer duration, and the use of beta2-agonist given after the study drug. MAIN RESULTS: Nineteen studies for single-dose treatment and 10 for treatment of longer duration met selection criteria. The patients had mild-moderate airways obstruction. For cardioselective beta1-blockers taken as a group, administration of a single dose was associated with a 7.98% (CI, 6.19 to 9.77%) reduction in FEV1, but with a 13.16% (CI, 10.76 to 15.56%) increase in beta2-agonist response, as compared to placebo. There was no increase in symptoms. After treatment lasting a few days to a few weeks, there was no decrement in FEV1 compared to placebo and no increase in symptoms or inhaler use. Regular use of cardioselective beta1-blockers without ISA produced a 13.13% (CI, 5.97 to 20.30) increase in beta2-agonist response compared to placebo, a response not seen with beta1-blockers containing ISA (-0.60% [CI, -11.7 to +10.5%]). REVIEWER'S CONCLUSIONS: Cardioselective beta1-blockers, given to patients with mild-moderate reversible airway disease, do not produce clinically significant adverse respiratory effects in the short term. It is not possible to comment on their effects in patient with more severe or less reversible disease, or on their effect on the frequency or severity of acute exacerbations. Given their demonstrated benefit in conditions such as heart failure, coronary artery disease and hypertension, cardioselective beta1-blockers should not be withheld from patients with mild-moderate reversible airway disease.

[The comparison of clinical effectiveness of perindopril and acebutolol in the primary hypertension treatment]. / Porównanie skutecznosci klinicznej perindoprilu i acebutololu w leczeniu pierwotnego nadcisnienia tetniczego.

Hypertension is one of the most important risk factors for ischaemic heart disease and stroke. The aim of our study was to assess the antihypertensive effect of angiotensine converting enzyme inhibitor (perindopril) versus beta blocker (acebutolol) in hypertensive patients. It was a double blind, placebo controlled study performed in the group of 31 patients (16 males, 15 females; mean age 46.6 +/- 8.7 years) with newly diagnosed (previously not treated) mild to moderate hypertension. Each patient in the wash-out period (two weeks) was given placebo and then was randomized to active treatment: perindopril (4 mg/day) or acebutolol (400 mg/day) for 3 weeks, following these drugs were cross matched (after one week wash out period). Blood pressure (BP) with mercury sphygmomanometer was measured three times: after 2 weeks of placebo treatment, after 3 weeks of perindopril and 3 weeks of acebutolol treatment. Both perindopril and acebutolol proved to be effective in monotherapy of hypertension. After 3 weeks of the treatment we observed BP systolic and diastolic normalization, but more patients had systolic BP normalization after perindopril treatment.

beta(1)-adrenergic antagonists improve sleep and behavioural disturbances in a circadian disorder, Smith-Magenis syndrome.

Smith-Magenis syndrome (SMS) is a clinically recognisable contiguous gene syndrome ascribed to interstitial deletions of chromosome 17p11.2. Patients have a phase shift of their circadian rhythm of melatonin with a paradoxical diurnal secretion of the hormone. Serum melatonin levels and day-night behaviour were studied in nine SMS children (aged 4 to 17 years) given acebutolol, a selective beta(1)-adrenergic antagonist (10 mg/kg early in the morning). Cardiac examination, serum melatonin, motor activity recordings, and sleep diaries were monitored before and after drug administration. The present study shows that a single morning dose of acebutolol suppressed the inappropriate secretion of melatonin in SMS. A significant improvement of inappropriate behaviour with increased concentration, delayed sleep onset, increased hours of sleep, and delayed waking were also noted. These results suggest that beta(1)-adrenergic antagonists help to manage hyperactivity, enhance cognitive performance, and reduce sleep disorders in SMS.