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Background: Polypharmacy is common in patients with dysphagia. Routinely used drugs may influence swallowing function either improving or worsening it. We aimed to explore the potential effects of three commonly used drug classes on dysphagia and aspiration pneumonia through a systematic review and a real-world data analysis to probe the possibility of drug repurposing for dysphagia treatment.Material and Methods: Five electronic databases were searched. Studies on adults at risk for dysphagia, treated with Dipeptidyl-Peptidase IV Inhibitors (DPP-4i), Adrenergic Beta-Antagonists (beta-blockers), or Angiotensin-Converting Enzyme Inhibitors (ACEi), and reporting outcomes on dysphagia or aspiration pneumonia were included. A nested case/non-case study was performed on adverse events recorded in the FDA Adverse Event Reporting System (FAERS) on patients >64 years. Cases (dysphagia or aspiration pneumonia) were compared between patients only treated with Levodopa and patients who were concomitantly treated with the drugs of interest.Results: Twenty studies were included in the review (17 on ACEi, 2 on beta-blockers, and 1 on DPP-4i). Contrasting findings on the effects of ACEi were found, with a protective effect mainly reported in Asian studies on neurological patients. Beta-blockers were associated with a reduced dysphagia rate. The study on DPP-4i suggested no effect on dysphagia and an increased risk of aspiration pneumonia. The FAERS analysis showed a reduction of the risk for dysphagia/aspiration pneumonia with ACEi, beta-blockers, and DPP-4i.Conclusion: Our study explores the potential drug repurposing of ACEi, beta-blockers and DPP-4i in neurological patients with dysphagia to improve swallowing function and reduce aspiration pneumonia risk. Future randomized controlled studies should confirm these results and clarify the underlying mechanisms of action.

Purpose High-dose insulin/euglycemia (HDIE) is targeted therapy for β-blocker and calcium channel blocker overdose. A guideline using concentrated insulin infusions (20 units/mL), aggressive monitoring, and supportive recommendations was implemented. We sought to evaluate safety before and after HDIE guideline implementation and describe the patient population, insulin doses, supplemental dextrose, vasopressor use, hospital and intensive care unit (ICU) lengths of stay, and mortality. Methods Retrospective review was performed of patients receiving HDIE before and after guideline implementation at an academic medical center and community hospital from March 2011 through December 2019. Information on patient and overdose demographics, ingestion data, vital signs, interventions, adverse events, and disposition was collected. Data are presented descriptively with comparisons using Mann-Whitney U analysis and Fisher's exact tests. Results During the study period, 27 patients were treated with HDIE, 10 before guideline implementation (37%; mean [SD] initial insulin dose, 0.49 [0.35] units/kg/h; mean [SD] maximum insulin dose, 2.25 [3.29] units/kg/h; median [interquartile range] duration, 10 [5.5-18.75] hours) and 17 after guideline implementation (63%; mean [SD] initial insulin dose, 1.01 [0.34] units/kg/h; mean [SD] maximum insulin dose, 2.99 [5.05] unit/kg/h; median [interquartile range] duration, 16 [11.5-37] hours). Hypoglycemia, hypokalemia, and volume overload occurred in 80% vs 29% (P = 0.018), 40% vs 53% (P = 0.69), and 50% vs 65% (P = 0.69) of patients in the preguideline vs postguideline group, respectively. Most patients received an initial insulin bolus (85%; mean [SD], 70.3 [21.8] units, 0.9 [0.26] units/kg) and vasopressor infusion (85%). More postguideline patients received a dextrose infusion with a concentration of 20% or higher (93% vs 50%, P = 0.015). There were no differences in cardiac arrest, in-hospital mortality, or hospital or ICU length of stay between the groups. Conclusion Hypoglycemia was reduced using an HDIE guideline and concentrated insulin. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the evidence for common therapeutic controversies in the medical management of valvular heart disease (VHD). Data Sources: A literature search of PubMed (inception to December 2020) was performed using the terms angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) and aortic stenosis (AS); and adrenergic β-antagonists and aortic valve regurgitation (AR) or mitral stenosis (MS). Study Selection and Data Extraction: Randomized controlled trials (RCTs) and meta-analyses conducted in humans and published in English that reported ≥1 clinical outcome were included. Data Synthesis: Nine articles were included: 3 RCTs and 1 meta-analysis for ACE inhibitors/ARBs in AS, 1 RCT for β-blockers in AR, and 4 RCTs for β-blockers in MS. Evidence suggests that ACE inhibitors/ARBs do not increase the risk of adverse outcomes in patients with AS but may delay valve replacement. β-Blockers do not appear to worsen outcomes in patients with chronic AR and may improve left-ventricular function in patients with a reduced ejection fraction. β-Blockers do not improve and may actually worsen exercise tolerance in patients with MS in sinus rhythm. Relevance to Patient Care and Clinical Practice: ACE inhibitors/ARBs and β-blockers can likely be safely used in patients with AS or AR, respectively, who have a compelling indication. There is insufficient evidence to recommend routine use of β-blockers in patients with MS without atrial fibrillation. Conclusions: Common beliefs about the medical treatment of VHD are not supported by high-quality data. There remains a need for larger-scale RCTs in the medical management of VHD. [ABSTRACT FROM AUTHOR]

Background: Postoperative atrial fibrillation (POAF) is the most common complication occurring after cardiac surgery. Guidelines for the management of this complication are scarce, often resulting in differences in treatment strategy use among patients.Objective: To evaluate the management of POAF in a cardiac surgery department, characterize the extent of its variability, and develop a standardized protocol.Methods: This was an observational retrospective study with data from patients who underwent cardiac surgeries with subsequent POAF between January 1, 2017, and June 1, 2018. We assessed the difference in the proportions of patients whose first POAF episodes were treated with a rate control (RaC) strategy, a rhythm control (RhC) strategy, and both among different hospital units. We also assessed the mean duration of POAF episodes, POAF recurrences, and the management of anticoagulation.Results: Data from 97 patients were included in this study. The POAF management strategy differed significantly among the 3 types of hospital units (P = 0.001). Considering all POAF episodes (including all recurrences), 83 of the 97 patients (85.6%) received amiodarone as part of the RhC strategy. Anticoagulation was used in 58 (59.8%) patients and was suboptimal according to the study criteria in 29.5% of the patients included. Based on these results, a hospital working group developed a standardized protocol for POAF management.Conclusions and Relevance: POAF management was heterogeneous at our institution. This article highlights the need for clear practice guidelines based on large prospective studies to provide care according to best practices. [ABSTRACT FROM AUTHOR]

Background: The adverse effects of long-term maternal exposure of labetalol on neonates have been recognized clinically. But there are few systematic studies on their clinical demonstrations and potential mechanisms.Methods: A death case of an infant with long-term maternal labetalol exposure was reported and compared with two case reports from the literature. A systematic literature review was carried out followed by a retrospective analysis on neonatal labetalol withdrawal effects.Results: It was discovered that labetalol withdrawal effects initially cause various degrees of hypotension, hypoglycemia, and bradycardia among exposed neonates. Some life-threatening cases can also occur within 1 week after birth. Long-term maternal exposure of labetalol, preterm infants with birth asphyxia, acidosis, hypoalbuminemia, and cardiac defects are their primary features. Possible mechanisms were concluded as labetalol-induced effects on the vascular and sympathetic nervous system as well as tissue oxygen extraction.Conclusions: Neonatal labetalol withdrawal effects include early-onset and late-onset demonstrations, the latter can be life-threatening. A possible mechanism is multiple factors induced imbalance of sympathetic homeostasis increases neonatal vulnerability to common stresses. Long-term exposed preterm infants complicated with asphyxia, acidosis, hypoalbuminemia and cardiac defects, should be provided with intense care during the first week after birth. Further work is necessary to enrich this hypothesis. [ABSTRACT FROM AUTHOR]

Right heart function is the main determinant of prognosis in pulmonary arterial hypertension (PAH). At present, no treatments are currently available that directly target the right ventricle, as we will demonstrate in this article. Meta-analysis of clinical trials in PAH revealed that current PAH medication seems to have limited cardiac-specific effects when analysed by the pump-function graph. Driven by the hypothesis that "left" and right heart failure might share important underlying pathophysiological mechanisms, we evaluated the clinical potential of left heart failure (LHF) therapies for PAH, based on currently available literature. As in LHF, the sympathetic nervous system and the renin–angiotension–aldosterone system are highly activated in PAH. From LHF we know that intervening in this process, e.g. by angiotensin-converting enzyme inhibition or β-blockade, is beneficial in the long run. Therefore, these medications could be also beneficial in PAH. Furthermore, the incidence of sudden cardiac death in PAH could be reduced by implantable cardioverter-defibrillators. Finally, pilot studies have demonstrated that interventricular dyssynchrony, present at end-stage PAH, responded favourably to cardiac resynchronisation therapy as well. In conclusion, therapies for LHF might be relevant for PAH. However, before they can be implemented in PAH management, safety and efficacy should be evaluated first in well-designed clinical trials.

The author expresses his views to the study on the effect of long-term administration of TRV067, a novel ligand of the angiotensin II type 1 receptor on the structure and function of failing hearts in a genetic mouse model of dilated cardiomyopathy (DCM). He states how the study underscores the validity of a biased signaling approach in the treatment of DCM and enhances the prospect that the strategy may emerge with clinical relevance.

Purpose The purpose of this study is to describe the pharmacologic management of rate and rhythm and assess which factors are associated with the prescription of these drugs in patients with nonvalvular atrial fibrillation (AF) from the Effectiveness, Safety, and Costs in Atrial Fibrillation study. Methods This retrospective, cross-sectional study describes the pharmacologic rate and rhythm control management strategies adopted during 2012 in all patients diagnosed as having nonvalvular AF in 2007 to 2011. The data source is the Information System for the Improvement of Research in Primary Care database, which is based on primary care electronic health records. To answer the study objectives, 3 multivariate regression models to assess the independent factors associated with the prescription of these drugs were conducted for 2012. The rate and rhythm control drugs assessed were β-blockers, nondihydropyridine calcium channel blockers, antiarrhythmic agents, and digoxin. Findings A total of 21,304 patients were diagnosed as having nonvalvular AF; 11,638 (54.6%) had at least one heart rate measure during 2012. Of them, 7777 (66.8%) received one or more rate and/or rhythm control drugs during 2012. Most patients (5751 [73.9%] of 7777) received only one drug for rate and/or rhythm control. Rate control agents were the most frequently used in 2012, with β-blockers the most prescribed group (4091 patients [52.6%]). A variety of different variables were associated with the prescription of rate and/or rhythm control drugs in the multivariate regression models. Implications The most used pharmacologic treatment of rate and rhythm control in our AF population is β-blockers, indicating that a rate control strategy is preferred in our setting, as widely recommended. [ABSTRACT FROM AUTHOR]

Objective. To assess the effect of propranolol treatment on the hepatic venous pressure gradient (HVPG) and the relationship between native HVPG and the effect of propranolol in patients with cirrhosis and portal hypertension in a prospective, observational, single-center study. Material and methods. The HVPG was registered prospectively in 124 consecutive cirrhosis patients with and without treatment with propranolol 80 mg daily. Results. 41% of the patients responded to the treatment with the intended reduction of HVPG to <12 mm Hg and/or by >20%. The HVPG reduction was larger for higher native HVPG values ( p < 0.001). There was no significant relation between changes in heart rate and changes in HVPG ( p = 0.8). Conclusions. The high fraction of hemodynamic non-responders supports the rationale of measuring the HVPG with and without propranolol treatment to assist the clinical assessment and avoid meaningless and potentially harmful treatment. The positive association between a high native HVPG and propranolol-induced HVPG reduction indicates that pharmacological treatment also benefits patients with advanced portal hypertension. [ABSTRACT FROM AUTHOR]

Copyright of Der Internist is the property of Springer Nature 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.)

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmia syndrome characterized by bidirectional or polymorphic ventricular arrhythmias under conditions of increased sympathetic activity in young patients with structurally normal hearts. Patients with CPVT are at high risk of developing life-threatening ventricular arrhythmias when untreated. A wide variety of arrhythmic event rates on conventional therapy, with β-blockers as the cornerstone, has been reported. Here, we systematically review all available studies describing the efficacy of β-blocker therapy for prevention of arrhythmic events in CPVT. Because of heterogeneity between the studies, a random-effects meta-analysis model was used to assess the efficacy of β-blocker therapy in preventing any arrhythmic event [syncope, aborted cardiac arrest (ACA), and sudden cardiac death (SCD)], near-fatal arrhythmic events (ACA and SCD), and fatal arrhythmic events. Eleven studies including 403 patients, of whom 354 (88%) had a β-blocker prescribed, were identified. Mean follow-up ranged from 20 months to 8 years. Estimated 8-year arrhythmic, near-fatal, and fatal event rates were 37.2% [95% confidence interval (CI): 16.6–57.7], 15.3% (95% CI: 7.4–23.3), and 6.4% (95% CI: 3.2–9.6), respectively. In addition, we review the recent developments in alternate chronic treatment options for CPVT patients, including calcium channel blockers, flecainide, left cardiac sympathetic denervation, and implantable cardioverter defibrillators. A new treatment strategy is proposed, including a stepwise addition of the alternate treatment options to β-blockers in patients who do not respond sufficiently to this first-line therapy. Finally, future developments in chronic treatment options and acute treatment options of ventricular arrhythmias are discussed. [ABSTRACT FROM PUBLISHER]

Mode of death in chronic heart failure (CHF) may be of relevance to choice of therapy for this condition. Sudden death is particularly common in patients with early and/or mild/moderate CHF. β-Blockade may provide better protection against sudden death than ACE inhibition (ACEI) in this setting. We randomized 1010 patients with mild or moderate, stable CHF and left ventricular ejection fraction ≤35%, without ACEI, β-blocker or angiotensin-receptor-blocker therapy, to either bisoprolol (n = 505) or enalapril (n = 505) for 6 months, followed by their combination for 6-24 months. The two strategies were blindly compared regarding adjudicated mode of death, including sudden death and progressive pump failure death. During the monotherapy phase, 8 of 23 deaths in the bisoprolol-first group were sudden, compared to 16 of 32 in the enalapril-first group: hazard ratio (HR) for sudden death 0.50; 95% confidence interval (CI) 0.21-1.16; P= 0.107. At 1 year, 16 of 42 versus 29 of 60 deaths were sudden: HR 0.54; 95% CI 0.29-1.00; P= 0.049. At study end, 29 of 65 versus 34 of 73 deaths were sudden: HR 0.84; 95% CI 0.51-1.38; P= 0.487. Comparable figures for pump failure death were: monotherapy, 7 of 23 deaths versus 2 of 32: HR 3.43; 95% CI 0.71-16.53; P= 0.124, at 1 year, 13 of 42 versus 5 of 60: HR 2.57; 95% CI 0.92-7.20; P= 0.073, at study end, 17 of 65 versus 7 of 73: HR 2.39; 95% CI 0.99-5.75; P= 0.053. There were no significant between-group differences in any other fatal events. Initiating therapy with bisoprolol compared to enalapril decreased the risk of sudden death during the first year in this mild systolic CHF cohort. This was somewhat offset by an increase in pump failure deaths in the bisoprolol-first cohort. [ABSTRACT FROM AUTHOR]

Abstract: Background: Performance-measurement systems may work best when they account for the reasons why physicians do not provide guideline-recommended interventions. Objective: This article develops a conceptual framework for understanding the proximate, patient-centered reasons why physicians do not prescribe angiotensin-converting enzyme (ACE) inhibitors or β-blockers to patients with heart failure and reduced systolic function. Methods: This was a focus group study using a 2-stage design. Academically affiliated clinicians of different specialties and levels of training were recruited by e-mailed invitations sent to clinicians within each target group. To be included, candidates needed to be currently practicing in an ambulatory care setting in which they encountered patients with heart failure. In the first part of each group, participants were asked to describe reasons for not prescribing ACE inhibitors or â-blockers for patients with heart failure. Next, participants were asked to develop concept maps that organized these reasons into categories and described the relationships between these categories. The concept maps from each group were synthesized to develop a consensus scheme for categorizing reasons for nonprescribing. Results: There were 31 participants in 7 focus groups; median age was 31 years and 55% (17/31) were women. Two broad themes emerged. First, clinicians hinted at their own attitude-related barriers to prescribing. However, they framed their comments largely in terms of patient-centered reasons for nonprescribing that arose in individual patient encounters. Second, decision making about heart failure drug therapy often involved a complex and overlapping series of considerations. Five categories of reasons for not prescribing ACE inhibitors or â-blockers emerged: (1) adverse effects of drug therapy; (2) nonadherence to therapeutic and monitoring plan; (3) patients'' preferences and beliefs; (4) comanagement and transitions of care; and (5) prioritization and patient benefit. Conclusions: Physicians'' reasons for not prescribing guideline-recommended drugs for heart failure are complex but can be organized into a useful taxonomy. This taxonomy may be helpful for performance-measurement and quality-improvement programs that seek to understand reasons for physicians'' nonadherence to guidelines. [Copyright &y& Elsevier]

β-adrenoceptor blockade therapy was developed for the treatment of hypertension but is now also a cornerstone in the treatment of heart failure. Based on the mechanisms of action and current knowledge of pathway signaling, Ligget et al. hypothesized that genetic variants within G-protein coupled receptor kinases might alter disease course and response to β-adrenoceptor blockade therapy. Following a multistep approach, a common variant in GRK5 was identified as being important in vitro and in vivo (mouse model) in β-adrenergic desensitization, and was epidemiologically related to survival and therapy response in African-Americans. Although such a variety of research approaches is appealing, owing to the large number of used methods readers remain puzzled on some issues because it is not possible to give all details of each individual study. Therefore, interpretation of the overwhelming amount of results is difficult. In an era of shifting emphasis from classic hypothesis driven pharmacogenetics to genome-wide association studies, this study shows that hypothesis driven translational research is still of high value, especially in phenotypes as investigated here. [ABSTRACT FROM AUTHOR]

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Ivabradine is a new heart rate-lowering agent that acts specifically on the sinoatrial node via the If pacemaker channels. • Ivabradine has demonstrated similar efficacy to β-blockers. • As β-blockers are contraindicated in patients with obstructive airway disease, this study was conducted to assess the safety of ivabradine in patients with asthma. WHAT THIS STUDY ADDS • This study demonstrates that ivabradine has no effect on the pulmonary functions in patients with asthma and can be safely used a heart rate-lowering agent in patients with angina and coexistent airflow obstruction. AIM β-Blockers are commonly prescribed for stable angina and are recommended as initial therapy. However, β-blockers are contraindicated in patients with obstructive airway disease because of a risk of bronchoconstriction. Ivabradine is a specific heart rate-lowering agent that acts via If pacemaker channels in the sinoatrial node with no β-adrenoreceptor activity. Ivabradine has been recently approved for the treatment of stable angina. This study assessed the effects of repeated administration of ivabradine on lung function in patients with asthma. METHODS In this double-blind, placebo-controlled, crossover study, 20 subjects with asthma received either oral ivabradine 10 mg b.i.d. or placebo for 4.5 days. Forced expiratory volume in 1 s (FEV1) and peak expiratory flow rate (PEFR) were designated as the main outcome variable. Diary cards were used to monitor asthma symptoms on a five-point scale, rescue medication usage, and adverse events. RESULTS There were no significant differences in mean variation of FEV1 (ivabradine P = 0.664; placebo P = 0.652) or PEFR (ivabradine P = 0.153; placebo P = 0.356) from baseline following administration of ivabradine. There was also no significant difference in maximum percent variation in FEV1 or PEF between treatment groups ( P = 0.994; FEV1 and P = 0.704; PEF). On a similar note, there was no significant difference in asthma symptoms or rescue medication usage reported between the two groups. Adverse events were generally mild-to-moderate in intensity and no cardiovascular or serious adverse events were recorded. CONCLUSIONS This study confirms that ivabradine does not affect respiratory function or symptoms in patients with asthma and therefore represents a valuable therapeutic alternative to β-blockers for treating patients with stable angina and asthma. [ABSTRACT FROM AUTHOR]

Objectives: It was hypothesized that anesthesiologists’ decisions to provide perioperative β-blockade during vascular surgery would be influenced more by physician factors than by those of their patients. Design: Mail survey. Setting: Case presentation. Participants: Four hundred thirty-nine anesthesiologists in the United States who responded to a survey. Interventions: By using Microsoft Word Mail Merge (Microsoft, Redmond, WA), 6 factors in a hypothetical patient presenting for vascular surgery (sex, race, age, comorbidities, functional status, and magnitude of surgical stress) were randomly varied. Measurements and Main Results: The response rate was 22%. Self-reported propensity to use β-blockade was significantly increased among anesthesiologists who worked in New England, among those who worked in larger hospitals, or who had received fellowship training. Among healthy patients, β-blockers were more likely to be used for older than younger patients. Among sicker patients, however, the reverse was true. Heart rate triggers for β-blockade use were higher than heart rates associated with improved outcomes in pivotal β-blocker trials. Conclusions: Preferences for perioperative β-blockade use in vascular surgery patients are influenced by anesthesiologists’ demographics as well as patient comorbidities or degree of surgical stress. This finding suggests that efforts to increase perioperative β-blockade in high-risk vascular patients face significant barriers from some groups of clinicians. [Copyright &y& Elsevier]

Background: Clinical guidelines support the use of preoperative B-blocker in select patients. Patient safety groups have sought to measure the level of adherence to these recommendations.Objective: This study was performed to compare the utilization of preoperative B-blocker with current guidelines across multiple diverse institutions.Design: Retrospective chart review was performed of inpatients undergoing noncardiac surgery across 5 hospital centers during 2003 to 2004. The primary outcome of interest was the administration of preoperative B-blocker.Participants: The study sample included 1,304 randomly selected patients meeting the guideline criteria for preoperative B-blockade.Measurements and Main Results: Among patients meeting recommendations for preoperative B-blocker, only 44% (430/983) received B-blocker before surgery. Patients who had not previously received B-blocker were given B-blocker before surgery in only 14% (85/600) of cases. Target heart rates goals for perioperative B-blockade were achieved in 26% (113/430) of cases. Predictors for initiating preoperative B-blocker included nonelective surgery or a history of hypertension or diabetes. Individual hospitals were independently predictive of preoperative B-blocker administration in multivariable models.Conclusions: Preoperative B-blocker was significantly underutilized when compared with the current guideline recommendations. Target heart rate goals were not achieved in clinical practice, and few hospitalized patients had preoperative B-blockade initiated. The lack of adherence to preoperative B-blocker recommendations in practice may be impacted by ongoing clinical questions regarding the appropriate selection of candidates for this therapy. Further efforts toward achieving guideline recommendations for preoperative B-blocker use should be focused on the subset of patients that are uniformly agreed upon to be at high risk for cardiac events. [ABSTRACT FROM AUTHOR]

Context: Despite evidence of efficacy of antihypertensive agents in treating hypertensive patients, safety and efficacy of antihypertensive agents for coronary artery disease (CAD) have been discerned only from subgroup analyses in large trials. Objective: To compare mortality and morbidity outcomes in patients with hypertension and CAD treated with a calcium antagonist strategy (CAS) or a non–calcium antagonist strategy (NCAS). Design, Setting, and Participants: Randomized, open label, blinded end point study of 22 576 hypertensive CAD patients aged 50 years or older, which was conducted September 1997 to February 2003 at 862 sites in 14 countries. Interventions: Patients were randomly assigned to either CAS (verapamil sustained release) or NCAS (atenolol). Strategies specified dose and additional drug regimens. Trandolapril and/or hydrochlorothiazide was administered to achieve blood pressure goals according to guidelines from the sixth report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VI) of less than 140 mm Hg (systolic) and less than 90 mm Hg (diastolic); and less than 130 mm Hg (systolic) and less than 85 mm Hg (diastolic) if diabetes or renal impairment was present. Trandolapril was also recommended for patients with heart failure, diabetes, or renal impairment. Main Outcome Measures: Primary: first occurrence of death (all cause), nonfatal myocardial infarction, or nonfatal stroke; other: cardiovascular death, angina, adverse experiences, hospitalizations, and blood pressure control at 24 months. Results: At 24 months, in the CAS group, 6391 patients (81.5%) were taking verapamil sustained release; 4934 (62.9%) were taking trandolapril; and 3430 (43.7%) were taking hydrochlorothiazide. In the NCAS group, 6083 patients (77.5%) were taking atenolol; 4733 (60.3%) were taking hydrochlorothiazide; and 4113 (52.4%) were taking trandolapril. After a follow-up of 61 835 patient-years (mean, 2.7 years per patient), 2269 patients had a primary outcome event with no statistically significant difference between treatment strategies (9.93% in CAS and 10.17% in NCAS; relative risk [RR], 0.98; 95% confidence interval [CI], 0.90-1.06). Two-year blood pressure control was similar between groups. The JNC VI blood pressure goals were achieved by 65.0% (systolic) and 88.5% (diastolic) of CAS and 64.0% (systolic) and 88.1% (diastolic) of NCAS patients. A total of 71.7% of CAS and 70.7% of NCAS patients achieved a systolic blood pressure of less than 140 mm Hg and diastolic blood pressure of less than 90 mm Hg. Conclusion: The verapamil-trandolapril–based strategy was as clinically effective as the atenolol-hydrochlorothiazide–based strategy in hypertensive CAD patients. [ABSTRACT FROM AUTHOR]

Objectives: To determine the effect of commonly used minimally invasive treatments for clinically complete nonarteritic central retinal artery occlusion (CRAO) and design a prospective randomized trial to evaluate selective intra-arterial lysis for this condition. Methods: In this retrospective noncomparative case series, all medical records of patients with a diagnosis of CRAO treated at the Department of Ophthalmology, Ludwig-Maximilians-Universität, Munich, Germany, from 1994 through 1999 were reviewed for treatments administered and course of visual acuity. Main Outcome Measures: Best-corrected visual acuity (BCVA) at initial and last visit. Results: We identified 102 patient medical records; 71 were suitable for further analysis. Forty-four (62%) of the 71 patients included were treated with oral acetylsalicylate; 44 (62%), with oral acetazolamide; 32 (45%), with ocular massage; 22 (31%), with isovolemic hemodilution; 19 (27%), with oral pentoxifylline; 8 (11%), with topical β-blocker; 6 (8%), with paracentesis of the anterior chamber; 4 (6%), with subcutaneous heparin. A mean ± SD number of treatments of 2.5 ± 1.4 was administered per patient, and BCVA increased by a mean ± SD number of Snellen lines of 0.7 ± 2.8. The BCVA in 11 patients (15%) increased by 3 or more lines. Multivariate stepwise regression did not reveal any single or combination treatment as a significant factor for improvement in BCVA. Patient age and duration of visual impairment before initial examination were not significant predictors of final BCVA. Conclusions: Commonly used minimally invasive treatments of CRAO do not improve the natural course of the disease. A prospective trial by the European Assessment Group for Lysis in the Eye is under way to evaluate selective intra-arterial lysis, and in this trial some of these minimally invasive treatments are used in the control group. [ABSTRACT FROM AUTHOR]

The present study aimed to investigate expression of β2-adrenergic receptor (AR), the effect of the stress-related neurotransmitter norepinephrine (NE) on cell viability, proliferation and the therapeutic effect of propranolol, which is a typical β-blocker in various type of head and neck cancers for the first time. The β2-AR expression was investigated using immunohistochemistry and an immunoreactive scoring (IRS) system in 57 different head and neck cancer specimens, and reverse transcriptase-polymerase chain reaction and western blotting in four head and neck cancer cell lines (HNCCLs). Cell viability and proliferation assays were performed using 0, 1, 5 and 10 µM of NE and 1 µM of propranolol in four HNCCLs. The expression of β2-AR was positive in the majority of head and neck cancer tissues (55/57, 96.5%); however, it was significantly higher in oral cavity cancer than in pharyngeal cancer (median IRS: 9 vs. 3; P<0.001). All HNCCLs exhibited β2-AR expression, with a higher expression level detected in the oral cavity cancer cell line than in the others. NE stimulated viability (oral cavity, 206%; larynx, 156%; pharynx, 130%; nasal cavity, 137%; 10 µM NE) and proliferation (124, 176, 131 and 127%, respectively) in a dose-dependent manner in all HNCCLs. Conversely, propranolol attenuated such viability (55, 42, 18 and 22%, respectively) and proliferation (22, 40, 61 and 48%, respectively). In conclusion, the viability and proliferation of various head and neck cancers may be directly stimulated by stress and this may be attenuated by β-blockers. [ABSTRACT FROM AUTHOR]

Copyright of Notfall & Rettungsmedizin is the property of Springer Nature 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.)

Abstract: Heart failure (HF) and benign prostatic hypertrophy (BPH) are two conditions that commonly coexist in men 60 years and older. Carvedilol is the only β-adrenergic blocker approved for HF that also has additional α1-adrenergic blockade. As α1-adrenergic blockers are used in the treatment of BPH, it is intuitive that carvediolol could improve BPH symptoms. We present a case where carvedilol was replaced with bisoprolol resulting in acute urinary retention. When carvediolol was reinstituted, the patient''s symptoms of BPH resolved. Benign prostatic hypertrophy was later diagnosed by digital rectal exam. Six month after reinstituting the carvediolol, the patient remains free of his BPH symptoms. This case suggests that carvedilol may be considered for the management of HF with systolic dysfunction in patients with concomitant BPH thus eliminating the need for an α1-adrenergic blockers. [Copyright &y& Elsevier]

Objective: To review the research progress of adrenergic β-antagonists on wounds and diabetic chronic cutaneous ulcers healing in recent years, and to investigate its application prospect in diabetic foot ulcer (DFU)., Methods: The latest literature about the role of adrenergic β-antagonists in wounds and diabetic chronic cutaneous ulcers healing was extensively reviewed, and the mechanisms of adrenergic β-antagonists for wounds and its potential benefit for DFU were analyzed thoroughly., Results: The adrenergic β-antagonists can accelerate the wound healing. The possible mechanisms include accelerating re-epithelialization, promoting angiogenesis, improving neuropathy, and regulating inflammation and growth factors, etc . At present clinical research data showed that the adrenergic β-antagonists may be an adjuvant treatment for diabetic chronic cutaneous ulcers., Conclusion: Adrenergic β-antagonists maybe promote the healing of wounds and diabetic chronic cutaneous ulcers. However, more long-term follow-up and high-quality randomized control studies are needed to further verify their efficacy and safety for DFU.

Background: Preclinical studies suggest that β-blockers could exhibit anticancer properties in ovarian cancer. Similar effects have also been reported in observational studies, but their results remain inconsistent and could be impaired by methodological limitations. This study aimed to investigate whether β-blocker use is associated with improved survival in ovarian cancer patients at the Belgian population level., Methods: We conducted a population-based study by linking data of the Belgian Cancer Registry with medical claims data of the health insurance companies for patients diagnosed with ovarian cancer between 2004 and 2014. Information on ovarian-cancer-specific deaths was retrieved from mortality records collected by regional governments. Use of β-blockers was modelled as a time-varying covariate in Cox regression models to calculate adjusted hazards ratios (HRs) and 95% confidence intervals (95%CIs) for the association between postdiagnostic β-blocker exposure and overall or cancer-specific survival (OS and CSS, respectively). Adjustments were made for age at diagnosis, year of diagnosis, comorbidities, cancer stage, and cancer treatments., Results: In our population of 6197 patients, 2373 patients (38%) had at least one prescription of β-blockers in the 5 years following diagnosis. Postdiagnostic exposure to β-blockers was associated with a significant decrease in OS (adjusted HR, 1.21; 95%CI 1.12;1.30; p < 0.001) and CSS (adjusted HR, 1.17; 95%CI 1.07;1.29; p < 0.001). Moreover, this association remained similar in dose-response analyses, in subgroup analyses (including by β-blocker selectivity types), and in sensitivity analyses., Conclusion: In this large nationwide cohort of ovarian cancer patients, β-blocker users had reduced survival., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

A letter to the editor in response to the article "Risk-treatment mismatch in the pharmacotherapy of heart failure," by Douglas S. Lee and Jack V. Tu in the September 14, 2005 edition of "JAMA."

The author's response to a letter to the editor regarding the article "Risk-treatment mismatch in the pharmacotherapy of heart failure," by Douglas S. Lee and Jack V. Tu in the September 14, 2005 edition of "JAMA" is presented.

Aim: To investigate the effect of carvedilol on angiogenesis and the underlying signaling pathways., Methods: The effect of carvedilol on angiogenesis was examined using a human umbilical vascular endothelial cell (HUVEC) model. The effect of carvedilol on cell viability was measured by CCK8 assay. Flow cytometry was used to assess the effect of carvedilol on cell cycle progression. Cell migration, transwell migration and tube formation assays were performed to analyze the effect of carvedilol on HUVEC function. Vascular endothelial growth factor (VEGF) induced activation of HUVECs, which were pretreated with different carvedilol concentrations or none. Western blot analysis detected the phosphorylation levels of three cell signaling pathway proteins, VEGFR-2, Src, and extracellular signal-regulated kinase (ERK). The specific Src inhibitor PP2 was used to assess the role of Src in the VEGF-induced angiogenic pathway., Results: Carvedilol inhibited HUVEC proliferation in a dose-dependent manner (IC50 = 38.5 mmol/L). The distribution of cells in the S phase decreased from 43.6% to 37.2%, 35.6% and 17.8% by 1, 5 and 10 μmol/L carvedilol for 24 h, respectively. Carvedilol (10 μmol/L) reduced VEGF-induced HUVEC migration from 67.54 ± 7.83 to 37.11 ± 3.533 (P < 0.001). Carvedilol concentrations of 5 μmol/L and 10 μmol/L reduced cell invasion from 196.3% ± 18.76% to 114.0% ± 12.20% and 51.68% ± 8.28%, respectively. VEGF-induced tube formation was also reduced significantly by 5 μmol/L and 10 μmol/L carvedilol from 286.0 ± 36.72 to 135.7 ± 18.13 (P < 0.05) and 80.27 ± 11.16 (P < 0.01) respectively. We investigated several intracellular protein levels to determine the reason for these reductions. Treatment with 10 μmol/L carvedilol reduced VEGF-induced tyrosine phosphorylation of VEGFR-2 from 175.5% ± 8.54% to 52.67% ± 5.33% (P < 0.01). Additionally, 10 μmol/L carvedilol reduced VEGF-induced ERK 1/2 phosphorylation from 181.9% ± 18.61% to 56.45% ± 7.64% (P < 0.01). The VEGF-induced increase in Src kinase activity was alleviated by carvedilol [decreased from 141.8% ± 15.37% to 53.57 ± 7.18% (P < 0.01) and 47.04% ± 9.74% (P < 0.01) at concentrations of 5 and 10 μmol/L, respectively]. Pretreatment of HUVECs with Src kinase inhibitor almost completely prevented the VEGF-induced ERK upregulation [decreased from 213.2% ± 27.68% to 90.96% ± 17.16% (P < 0.01)]., Conclusion: Carvedilol has an anti-angiogenic effect on HUVECs. This inhibitory effect is mediated by VEGF-induced Src-ERK signaling pathways.

The cardiology literature has suggested for decades that β-blockade protects patients with ischaemic heart disease. Extending this concept to perioperative patients initially produced promising results, with reductions in perioperative myocardial ischaemia and longer-term cardiovascular complications observed in several small randomized trials. However, subsequent larger trials have either shown no benefit or greater morbidity (especially stroke), despite reductions in cardiovascular events. Retrospective database analyses have confirmed or disputed these findings. Speciality societies, most importantly, the American Heart Association/American College of Cardiology Foundation, have promulgated guidelines for perioperative β-blockade, which have been revised, as the evidence has changed. While the European guidelines continue to emphasize perioperative β-blockade in high-risk patients, the American guidelines have reduced the strength and breadth of recommendations, focusing on haemodynamic titration. Future work will need to focus on identifying populations most likely to benefit or to be harmed, including pharmacogenetic analyses and distinctions between individual β-blockers. [ABSTRACT FROM PUBLISHER]

Vasovagal syncope is a common cause of recurrent syncope. Clinically, these episodes may present as an isolated event with an identifiable trigger, or manifest as a cluster of recurrent episodes warranting intensive evaluation. The mechanism of vasovagal syncope is incompletely understood. Diagnostic tools such as implantable loop recorders may facilitate the identification of patients with arrhythmia mimicking benign vasovagal syncope. This review focuses on the management of vasovagal syncope and discusses the non-pharmacological and pharmacological treatment options, especially the use of midodrine and selective serotonin reuptake inhibitors. The role of cardiac pacing may be meaningful for a subgroup of patients who manifest severe bradycardia or asystole but this still remains controversial.