Type Of Beta-blocker Research Articles

The Effects of Beta-Blockers on Leukocytes and the Leukocyte Subpopulation in Heart Failure Patients.

Background/Objectives: Some specific types of white blood cells (WBCs) and the neutrophil/lymphocyte ratio (NLR) are independent predictors of outcome for heart failure (HF) patients. WBC redistribution is induced by catecholamines, and therefore we evaluate how different types of beta-blockers (BBs) influence it. Methods: The HF patients were clinically evaluated, and blood was drawn to measure N-Terminal pro-B-type natriuretic peptide (NT-proBNP), WBC-differential formula, etc. Results: On admission, 61.16% of patients who used a BB had no significant difference in the number of lymphocytes (Lym) and neutrophils (Neu), but NLR and NT- proBNP were significantly lower compared with those without BB. NT-proBNP correlated with BB dose on admission and was significantly lower in patients treated with Metoprolol (Met) as compared with Carvedilol (Car). The type and dose of BB used was responsible for 6.1% and 5.9% of the variability in the number of Lym and Neu, respectively. Patients treated with ≥100 mg Met/day had a higher Lym number, but not of Neu, with reduced NLR, compared with lower doses. Patients treated with ≥25 mg Car/day had a lower Lym number and a greater Neu number, compared with lower doses, with increased NLR. Conclusions: However, both BBs had the same rehospitalization rate during the 12 month follow-up and had an improved outcome.

The role of beta blockers in the treatment of cardiovascular diseases

Beta-blockers are used to treat various cardiovascular diseases, including hypertension and chronic heart failure. They act by suppressing the effects of catecholamines through various pathways and affect heart rate, strength, and renin release, providing antihypertensive and anti-ischemic effects. The individual effects of various drugs on clinical outcomes in this group were determined according to characteristics of the patient, underlying disease, and type of beta-blocker used. In recent years, beta-blockers have faced a serious obstacle when new guidelines on hypertension suggest their use as second-line therapy after angiotensin converting enzyme inhibitors, angiotensin receptor blockers and slow calcium channel blockers in the absence of clear indications. In fact, these recommendations were based on meta-analyses that showed that beta-blockers have fewer beneficial effects on overall mortality, cardiovascular events, and brain stroke. In addition, according to currently available data, the appointment of beta-blockers for diseases such as heart failure with preserved ejection fraction and stable coronary heart disease can cause more harm than good outcomes. Bisoprolol is a beta-blocker with the highest selectivity for beta1-adrenergic receptors, which determines the rare frequency of side effects that develop because of its use. This review presents current data on the use of beta-blockers for treating cardiovascular diseases, with an emphasis on the use of bisoprolol.

Impact of Beta-Blocker Therapy on Pregnant Women With Long QT Syndrome: A Systematic Review.

Long QT syndrome (LQTS) presents significant challenges for pregnant women due to the elevated risk of arrhythmic events. Beta-blocker therapy is a cornerstone of treatment in managing LQTS, but its use during pregnancy introduces potential fetal risks. This systematic review synthesizes the evidence on the efficacy and safety of beta-blocker therapy in pregnant women with LQTS. A systematic review was conducted to assess studies on beta-blocker use in pregnant women diagnosed with LQTS. We reviewed observational studies and case reports to evaluate maternal cardiac outcomes, fetal safety, and the need for postpartum management. Studies were selected based on inclusion criteria focused on LQTS, beta-blocker therapy during pregnancy, and associated maternal and fetal outcomes. Our review showed that beta-blocker therapy significantly reduced arrhythmic events in pregnant women with LQTS, particularly in symptomatic carriers. Multiple studies demonstrated that the continuation of beta-blocker therapy throughout pregnancy and the postpartum period minimized maternal cardiac risks. However, beta-blocker use was associated with fetal risks such as intrauterine growth restriction (IUGR), lower birth weight, and, in some cases, bradycardia. Atenolol, in particular, was linked to significant fetal growth restrictions, while other beta-blockers, such as propranolol and metoprolol, showed more variable effects on fetal outcomes. Despite these concerns, some studies reported favorable postnatal growth recovery in infants exposed to beta-blockers in utero. Beta-blocker use must be carefully managed due to potential fetal risks. Regular monitoring, individualized treatment plans, and appropriate selection of beta-blocker type are essential to optimizing both maternal and fetal outcomes. Further research is necessary to refine treatment protocols and reduce fetal risks associated with beta-blocker therapy during pregnancy.

Repurposing beta-blockers for combinatory cancer treatment: effects on conventional and immune therapies.

Beta-adrenergic receptor signaling regulates cellular processes associated with facilitating tumor cell proliferation and dampening anti-tumor immune response. These cellular processes may lead to compromised tumor control and cancer progression. Based on this ramification, Beta-blockers (BBs) have emerged as a potential treatment by inhibiting beta-adrenergic receptor signaling. This review aimed to investigate the relationship between the use of BBs and tumor progression and treatment response. Therefore, the authors explored several aspects: the potential synergistic relationship of BBs with chemotherapy and immunotherapy in enhancing the effectiveness of chemotherapeutic and immunotherapeutic treatments and their role in boosting endogenous immunity. Further, this review explores the distinctions between the major types of BBs: Non-selective Beta Blockers (NSBBs) and Selective Beta Blockers (SBBs), and their contributions to combinatory cancer treatment. In this review, we presented a perspective interpretation of research findings and future directions. Overall, this review discusses the potential and challenge that BBs present in improving the effectiveness and outcome of cancer treatment.

The association betweenbeta-blockers use and prostate cancer mortality: A mini systematic review and meta-analysis.

Preclinical studies have shown that the sympathetic nervous system is involved in the development of metastases, suggesting a potential antitumor effect of beta-blockers. These findings sparked a controversy over the past decade regarding the direction of the association between beta-blocker use and prostate cancer (PCa) mortality. To investigate this association, we conducted a systematic review and meta-analysis. The review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-analysesguidelines to identify eligible studies. The primary outcome was PCa mortality in beta-blocker users versus nonusers, and overall survival was studied as a secondary endpoint. We assessed heterogeneity using the Cochrane Q test and quantified it using I2 values. In the case of heterogeneity (Cochrane Q test p < 0.05 and I2 > 50%), random-effect models were used to determine the association between beta-blockers use and survival outcomes. Ten studies met our inclusion criteria and a total of 74,970 patients were included: 26,674 beta-blocker users and 48,326 nonusers. There was no statistically significant association between beta-blocker exposure and PCa mortality (hazard ratio [HR] 0.97; 95% confidence interval [CI] 0.87-1.09; p = 0.61). However, significant heterogeneity was found. Meta-regression analysis to explain heterogeneity showed no effect of any of the variables assessed (country, percentage of beta-blocker users, type of beta-blocker [selective and nonselective], study period, PCa stage and follow-up duration; all p > 0.05). We found similar results when we restricted the analysis to studies that include only patients with advanced PCa (HR 0.92; 95% CI 0.80-1.06; p = 0.24). Similarly, we found no association with overall survival (HR 1.02; 95% CI 0.94-1.10; p = 0.64). Meta-regression analysis was also performed, but none of the variables assessed explained the observed heterogeneity (all p > 0.05). We found no association between beta-blockers use and overall survival or PCa mortality. This meta-analysis, which includes a considerable population and the most recent literature, provides important data for routine clinical care and patient counseling.

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

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

Effect of Carvedilol vs Metoprolol on Atrial and Ventricular Arrhythmias Among Implantable Cardioverter-Defibrillator Recipients

BackgroundBoth selective and nonselective beta-blockers are used to treat patients with heart failure (HF). However, the data on the association of beta-blocker type with risk of atrial arrhythmia and ventricular arrhythmia (VA) in HF patients with a primary prevention implantable cardioverter-defibrillator (ICD) are limited. ObjectivesThis study sought to evaluate the effect of metoprolol vs carvedilol on the risk of atrial tachyarrhythmia (ATA) and VA in HF patients with an ICD. MethodsThis study pooled primary prevention ICD recipients from 5 landmark ICD trials (MADIT-II, MADIT-CRT, MADIT-RIT, MADIT-RISK, and RAID). Fine and Gray multivariate regression models, stratified by study, were used to evaluate the risk of ATA, inappropriate ICD shocks, and fast VA (defined as ventricular tachycardia ≥200 beats/min or ventricular fibrillation) by beta-blocker type. ResultsAmong 4,194 patients, 2,920 (70%) were prescribed carvedilol and 1,274 (30%) metoprolol. The cumulative incidence of ATA at 3.5 years was 11% in patients treated with carvedilol vs 15% in patients taking metoprolol (P = 0.003). Multivariate analysis showed that carvedilol treatment was associated with a 35% reduction in the risk of ATA (HR: 0.65; 95% CI: 0.53-0.81; P < 0.001) when compared to metoprolol, and with a corresponding 35% reduction in the risk of inappropriate ICD shocks (HR: 0.65; 95% CI: 0.47-0.89; P = 0.008). Carvedilol vs metoprolol was also associated with a 16% reduction in the risk of fast VA. However, these findings did not reach statistical significance (HR: 0.84; 95% CI: 0.70-1.02; P = 0.085). ConclusionsThese findings suggests that HF patients with ICDs on carvedilol treatment experience a significantly lower risk of ATA and inappropriate ICD shocks when compared to treatment with metoprolol.

Using administrative healthcare data to evaluate drug repurposing opportunities for cancer: the possibility of using beta-blockers to treat breast cancer.

Introduction: Cancer registries and hospital electronic medical records are commonly used to investigate drug repurposing candidates for cancer. However, administrative data are often more accessible than data from cancer registries and medical records. Therefore, we evaluated if administrative data could be used to evaluate drug repurposing for cancer by conducting an example study on the association between beta-blocker use and breast cancer mortality. Methods: A retrospective cohort study of women aged ≥50years with incident breast cancer was conducted using a linked dataset with statewide hospital admission data and nationwide medication claims data. Women receiving beta blockers and first-line anti-hypertensives prior to and at diagnosis were compared. Breast cancer molecular subtypes and metastasis status were inferred by algorithms from commonly prescribed breast cancer antineoplastics and hospitalization diagnosis codes, respectively. Subdistribution hazard ratios (sHR) and corresponding 95% confidence intervals (CIs) for breast cancer mortality were estimated using Fine and Gray's competing risk models adjusted for age, Charlson comorbidity index, congestive heart failure, myocardial infraction, molecular subtype, presence of metastasis at diagnosis, and breast cancer surgery. Results: 2,758 women were hospitalized for incident breast cancer. 604 received beta-blockers and 1,387 received first-line antihypertensives. In total, 154 breast cancer deaths were identified over a median follow-up time of 2.7years. We found no significant association between use of any beta-blocker and breast-cancer mortality (sHR 0.86, 95%CI 0.58-1.28), or when stratified by beta-blocker type (non-selective, sHR 0.42, 95%CI 0.14-1.25; selective, sHR 0.95, 95%CI 0.63-1.43). Results were not significant when stratified by molecular subtypes (e.g., triple negative breast cancer (TNBC), any beta blocker, sHR 0.16, 95%CI 0.02-1.51). Discussion: It is possible to use administrative data to explore drug repurposing opportunities. Although non-significant, an indication of an association was found for the TNBC subtype, which aligns with previous studies using registry data. Future studies with larger sample size, longer follow-up are required to confirm the association, and linkage to clinical data sources are required to validate our methodologies.

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

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

Beta blockers reduce uterine fibroid incidence in hypertensive women

ObjectiveIs prior beta blocker (BB) use associated with reduced odds of the clinical incidence of leiomyomas? What is known alreadyIn-vitro and in-vivo evidence has supported the role of beta receptor blockade in reducing leiomyoma cell proliferation and growth. However, no population-based study to date has investigated this potential association. Study design, size, durationA nested case-control study was conducted in a population of women aged 18–65 with arterial hypertension (n = 699,966). Cases (n = 18,918) with a leiomyoma diagnosis were matched to controls (n = 681,048) with no such diagnosis at a 1:36 ratio by age and region of origin within the United States. Participants/materials, setting, methodsThis population was assembled from the Truven Health MarketScan® Research Database, which includes health insurance claims from January 1st, 2012 to December 31st, 2017. Prior use of BB wasdetermined fromoutpatient drug claims and leiomyoma development was indicated by a first-time diagnosis code. We conducted a conditional logistic regression to determine the odds of uterine fibroid development in women with prior use of BB compared to women with no such history. We then conducted subset analyses, stratifying the women by age group and by type of BB. ResultsWomen on a BB experienced 15% reduced odds of developing clinically recognized leiomyoma compared to non-users (OR 0.85, 95% CI 0.76–0.94). This association was significant for the 30–39 age group (OR 0.61, 95% CI 0.40–0.93) but no other age group. Of the BBs, propranolol (OR 0.58, 95% CI 0.36–95) demonstrated a significant association with reduced leiomyoma incidence and metoprolol (OR 0.82, 95% CI 0.70–0.97) was associated with lower uterine fibroid incidence after adjustment for comorbidities. ConclusionsHypertensive women with prior BB use experienced reduced odds of developing clinically recognized leiomyoma compared to non-users. A key predisposing risk factor for uterine leiomyoma is elevated blood pressure. Thus, the results of this analysis may have clinical relevance to women with hypertension, as the use of this drug may introduce a dual benefit of managing hypertension as well as curbing an increased risk of leiomyomas.

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

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

Impact of type of dialyzable beta-blockers on subsequent risk of mortality in patients receiving dialysis: A systematic review and meta-analysis.

Beta-blockers has been reported to improve all-cause mortality and cardiovascular mortality in patients receiving dialysis, but type of beta-blockers (i.e., high vs. low dialyzable) on patient outcomes remains unknown. This study aimed at assessing the outcomes of patients receiving dialyzable beta-blockers (DBBs) compared to those receiving non-dialyzable beta-blockers (NDBBs). We searched the databases including PubMed, Embase, Cochrane, and ClinicalTrials.gov until 28 February 2022 to identify articles investigating the impact of DBBs/NDBBs among patients with renal failure receiving hemodialysis/peritoneal dialysis (HD/PD). The primary outcome was risks of all-cause mortality, while the secondary outcomes included risk of overall major adverse cardiac event (MACE), acute myocardial infarction (AMI) and heart failure (HF). We rated the certainty of evidence (COE) by Cochrane methods and the GRADE approach. Analysis of four observational studies including 75,193 individuals undergoing dialysis in hospital and community settings after a follow-up from 180 days to six years showed an overall all-cause mortality rate of 11.56% (DBBs and NDBBs: 12.32% and 10.7%, respectively) without significant differences in risks of mortality between the two groups [random effect, aHR 0.91 (95% CI, 0.81-1.02), p = 0.11], overall MACE [OR 1.03 (95% CI, 0.78-1.38), p = 0.82], and AMI [OR 1.02 (95% CI, 0.94-1.1), p = 0.66]. Nevertheless, the pooled odds ratio of HF among patients receiving DBBs was lower than those receiving NDBB [random effect, OR 0.87 (95% CI, 0.82-0.93), p<0.001]. The COE was considered low for overall MACE, AMI and HF, while it was deemed moderate for all-cause mortality. The use of dialyzable and non-dialyzable beta-blockers had no impact on the risk of all-cause mortality, overall MACE, and AMI among dialysis patients. However, DBBs were associated with significant reduction in risk of HF compared with NDBBs. The limited number of available studies warranted further large-scale clinical investigations to support our findings.

Abstract 15723: Risk Factors for Beta-Blockers Failure in Catecholaminergic Polymorphic Ventricular Tachycardia

Introduction: Patients with Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT) may experience life-threatening arrhythmic events (LAE) despite standard-of-care treatment with beta-blockers (BB), but risk stratification is not well defined. Hypothesis: Both clinical and genetic risk factors predispose to BB failure, including the class of BBs (β1-selective vs. non-selective). Methods: LAE was defined as the composite of sudden cardiac death, aborted cardiac arrest, or hemodynamically non-tolerated ventricular tachycardia. We fitted a Cox proportional hazards regression model with multiple events during BB treatment only with the following explanatory covariates: 1) LAE before diagnosis, 2) unexplained syncope before diagnosis, 3) genotype, and 4) type of BB (as time-dependent variable). Results: We included n=238 CPVT patients: n=135 (57%) probands, n=134 (56%) females, n=216 (91%) RYR2, n=10 (4%) CASQ2, n=5 (2%) RYR2-Loss-of-Function, n=4 (2%) TRDN and n=3 (1%) TECRL. Before the diagnosis, 48/238 (20%) patients experienced an LAE, while 110/238 (46%) patients experienced an unexplained syncope. During a mean follow-up of 9.7±7.6 years of treatment with BB only, 35/238 (15%) patients experienced one or more LAEs (annual rate 4.0%, 95% CI: 3.1%-5.0%), with a mean of 2.1±2.4 LAEs per patient. Multivariable analysis with multiple events at follow-up showed that LAE before diagnosis (HR 3.9; 95%CI: 2.3-6.8; p&lt;0.001), syncope before diagnosis (HR 2.7; 95%CI: 1.5-5.0; p=0.001), TRDN mutations (HR 10.9; 95%CI: 4.2-28.0; p&lt;0.001) and use of β1-selective BBs (HR 3.0; 95%CI: 1.7-5.3; p&lt;0.001) were significantly associated with the occurrence of LAE (Figure). Conclusions: In patients with CPVT, history of LAE and/or unexplained syncope before diagnosis, TRDN mutations and the use of selective BBs are independent risk factors for the occurrence of multiple LAEs at follow-up during BB treatment.

Aesthetic Outcome of Propranolol vs Atenolol Treatment of Children with Infantile Haemangioma.

Infantile haemangiomas are common benign tumours of infancy, which can be treated effectively with beta-blockers such as propranolol and atenolol. Different types of beta-blockers may result in different long-term aesthetic outcomes. This study evaluated the difference in long-term aesthetic outcomes between infantile haemangiomas treated with either propranolol or atenolol, including the perspective of physicians, parents, and children. Children, aged ≥6 years, treated with propranolol or atenolol for infantile haemangioma during infancy, participated in this 2-centre cross-sectional study. The primary endpoint was change in appearance of the infantile haemangioma from pre-treatment to follow-up, using a physician-rated visual analogue scale (VAS). Secondary outcomes were the Patient Observer Scar Assessment Scale (physician- and parent-rated) and a VAS (child-rated), assessing the residual lesion. In total, 103 children (35 treated with propranolol, 68 with atenolol) were analysed. No differences were found between children treated with propranolol and children treated with atenolol on physician-rated VAS (p = 0.10) or any secondary outcomes. Physicians indicated a large aesthetic improve-ment from pre- treatment to follow-up. Physicians, parents and children were positive about the current state of the residual lesion. Minor sequelae were common (86%). These results, in combination with the favourable safety profile of atenolol, should be considered when choosing beta-blocker treatment for infantile haemangioma.

An Update on the Use of Molecularly Imprinted Polymers in Beta-Blocker Drug Analysis as a Selective Separation Method in Biological and Environmental Analysis.

Beta-blockers are antihypertensive drugs and can be abused by athletes in some sport competitions; it is therefore necessary to monitor beta-blocker levels in biological samples. In addition, beta-blocker levels in environmental samples need to be monitored to determine whether there are contaminants from the activities of the pharmaceutical industry. Several extraction methods have been developed to separate beta-blocker drugs in a sample, one of which is molecularly imprinted polymer solid-phase extraction (MIP-SPE). MIPs have some advantages, including good selectivity, high affinity, ease of synthesis, and low cost. This review provides an overview of the polymerization methods for synthesizing MIPs of beta-blocker groups. The methods that are still widely used to synthesize MIPs for beta-blockers are the bulk polymerization method and the precipitation polymerization method. MIPs for beta-blockers still need further development, especially since many types of beta-blockers have not been used as templates in the MIP synthesis process and modification of the MIP sorbent is required, to obtain high throughput analysis.

Investigating the biological degradation of the drug β-blocker atenolol from wastewater using the SBR.

Drug compounds are one of the main contributors to the entry of micro-pollutants into the environment, known as a constant threat to environmental stability. Atenolol is a type of beta-blocker extensively used to cure cardiovascular disorders. The residues of this compound have been continuously detected in aquatic environments because it is a polar and poorly biodegradable compound. Thus, removing atenolol from wastewater is essential before discharging into the environment. Biological processes are considered the most important removal process for polar drugs in wastewater treatment plants. Accordingly, for the first time in this study, the SBR performance was investigated in the biodegradation and mineralization of atenolol under different concentrations (50-600mg/L) and hydraulic retention times (48-32h). Based on the results, the time required for the acclimation of biomass to atenolol (C: 50mg/L and the HRT: 48h) was 80 days. The SBR efficiencies under optimum conditions (C: 400mg/L and HRT: 40h) in removing the atenolol and COD were 91% and 87%, respectively. For the first time in this study, one of the main pathways of the atenolol biodegradation was identified. Based on the review and comparison of the results of this study with existing literature showing that the SBR used in this study was able to remove higher concentrations with better efficiencies than other processes. Therefore, it can be concluded that the SBR used in this study could be considered an efficient and promising technique for treating wastewaters containing atenolol and other beta-blocker group drugs.

Beta blockers and long-term outcome after coronary artery bypass grafting: a nationwide observational study.

AimsBeta blockers are associated with improved outcomes for selected patients with cardiovascular disease. We assessed long-term utilization of beta blockers after coronary artery bypass grafting (CABG) and its association with outcome.Methods and resultsAll 35 184 patients in Sweden who underwent first-time isolated CABG between 1 January 2006 and 31 December 2017 and were followed for at least 6 months were included in a nationwide observational study. Multivariable Cox regression models using time-updated data on dispensed prescriptions were used to assess associations between different types of beta blockers and outcomes. The primary outcome was major adverse cardiovascular events (MACEs), a composite of all-cause mortality, stroke, and myocardial infarction (MI). Subgroup analyses were performed in patients with and without previous MI, heart failure, and reduced left ventricular ejection fraction (LVEF). Median follow-up was 5.2 years (range 0–11). At baseline, 33 159 (94.2%) patients were dispensed beta blockers, 30 563 (92.2%) of which were cardioselective beta blockers. After 10 years, the dispensing of cardioselective beta blockers had declined to 73.7% of all patients. Ongoing treatment with cardioselective beta blockers was associated with a slight reduction in MACEs [hazard ratio (HR) 0.93, 95% confidence interval (CI) 0.89–0.98, P = 0.0063]. The reduction was largely driven by a reduced risk of MI (HR 0.83, 95% CI 0.75–0.92, P = 0.0003), while there was no significant reduction in all-cause mortality (HR 0.99, 95% CI 0.93–1.05) and stroke (HR 0.96, 95% CI 0.87–1.05). The reduced risk for MI was consistent in all the investigated subgroups.ConclusionOngoing treatment with cardioselective beta blockers after CABG is associated with a reduction in MACEs, mainly because of reduced long-term risk for MI. The association between cardioselective beta blockers and MI was consistent in patients with and patients without previous MI, heart failure, atrial fibrillation, or reduced LVEF.

Use of beta-blockers and risk of contralateral breast cancer.

Beta-blockers have shown antineoplastic effects in laboratory studies but epidemiologic evidence in relation to contralateral breast cancer (CBC) is sparse. We investigated postdiagnosis beta-blocker use and risk of CBC in a cohort of 52 723 women with breast cancer by using nationwide Danish health registers and the Danish Breast Cancer Group database. We defined postdiagnosis beta-blocker use as a time-varying covariate starting 1 year after a second prescription was redeemed. Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for CBC associated with beta-blocker use compared to nonuse. We identified 1444 women with CBC of whom 209 women were beta-blocker users. We found an overall HR of 1.08 (95% CI: 0.93-1.27) for beta-blocker use and risk of CBC with no substantial variation according to cumulative amount, intensity or selectivity of beta-blocker use. Hence, our cohort study of women with breast cancer did not sustain a protective effect of beta-blocker use on risk of CBC, irrespective of beta-blocker type.

338 Autonomic function and hyper-adrenergic tone despite beta-blockers in chronic coronary syndrome with preserved ejection fraction: prevalence and related factors

Abstract Aims Autonomic dysfunction is a prevalent and independent risk factor for adverse cardiovascular events and mortality in chronic coronary syndrome (CCS). Beta-blockers (BB), directly inhibiting adrenergic receptors, have been associated with a significant reduction in mortality and/or cardiovascular events in patients with recent acute coronary syndrome (ACS) or in those with heart failure (HF) with reduced left ventricular ejection fraction (LV-EF); on the other hand, the protective benefit in CCS patients without prior ACS or HF is less well established and lacks placebo-controlled trials. The aim of the study was to investigate the prevalence of hyper-adrenergic tone in CCS with preserved LV-EF in patients with or without BB as well as to assess related factors of hyper-adrenergic tone despite BB. Methods A total of 165 consecutive CCS patients have been enrolled. Inclusion criteria were documented coronary artery disease and preserved left-ventricular ejection fraction (&amp;gt;50%). Exclusion criteria were: recent ACS (&amp;lt;6 months), HF symptoms (NYHA &amp;gt;1) and atrial fibrillation. According to Heart rate variability (HRV) guidelines, 5 min beat-to-beat analysis was performed in order to assess sympatho-vagal balance (without BB wash-out). Patients were then divided into in two groups: hyper adrenergic tone (LF/HF &amp;gt; 2.01) and normal adrenergic tone (LF/HF &amp;lt; 2.01). Moreover, patients with hyper-adrenergic tone despite BB were classified as ‘BB non-responders’ while patients with normal adrenergic tone as ‘BB responders’. Results Mean age was 64 ± 12 years and male gender was prevalent (75%). Patients treated with BB were 56% and the majority (96%) were treated with high selective. Overall hyper adrenergic tone (isolated or associated with blunted vagal tone) was found in 47% of CCS patients and no difference was found in the percentage of hyper-adrenergic tone between patients with or without beta-blockers (45% vs. 55% P = 0.716). Within the BB groups, 89% had heart rate at target (&amp;lt;70 b.p.m.), while only 11% showed heart rate not at target (&amp;gt;70 b.p.m.). Among the heart rate not at target 80% had hyper-adrenergic tone despite beta-blockers (non-responders); on the other hand, among the heart rate not at target hyper-adrenergic tone despite beta-blockers was found in 43%. No differences in types of BB (metoprolol vs. bisoprolol) between BB responders and non-responders was found (P = 0.714). Higher left atrial volume index (36 ± 8 vs. 42 ± 14; P = 0.029) and E/e’ ratio (an echocardiographic marker of high left ventricular filling pressure) (9.4 ± 2.1 vs. 7.4 ± 2.1; P = 0.038) were found in patients with hyper-adrenergic tone despite beta-blockers (non-responder). Moreover, a trend toward significance of higher Lown’s arrhythmic risk was found in non-responders (19% vs. 8%; P = 0.066) (Figure). Finally, Beta-blockers patients with bradycardia and hyper-adrenergic tone (non-responders) had higher prevalence of carotid artery disease (64% vs. 44%; P = 0.047), where baroreceptors are located. Conclusion The prevalence of hyper-adrenergic tone is high in CCS patients with preserved ejection fraction; about half of patients treated with beta-blockers had residual hyper-adrenergic tone (non-responders). Hyper-adrenergic tone in BB patients is higher in those with 24-h heart rate not at target (&amp;gt;70 b.p.m.), thereby suitable of BB titration, as well as in those with diastolic dysfunction or with carotid artery disease, where baroceptors are located.

Abstract 10411: Recurrent Spontaneous Coronary Artery Dissection

Spontaneous coronary dissection (SCAD) accounts for 25% of ACS in females &lt;50 years of age. The recurrence rate of SCAD within one to two years is 11%. Currently, there are no universal guidelines for the treatment of SCAD. However, the literature reports higher rates of complications associated with stenting than with medical treatment. Beta-blockers are believed to be protective against SCAD recurrence due to its direct mechanism of action on the vasculature and heart. The following case describes a patient on recommended medical therapy, including a beta-blocker who presented with a dissection of the second diagonal branch. A 51-year-old female with a history of SCAD in 2007 and right MCA aneurysm on metoprolol, presented with sudden onset of mid-sternal chest pain radiating to the back. The initial EKG showed T wave inversions in lead V2-V3 and elevated troponin of 2.58 which peaked at 9.9. The patient immediately underwent cardiac catheterization which revealed spontaneous dissection in the circumflex marginal. An ECHO revealed EF of 60-65% without wall motion abnormalities. The patient was treated medically with DAPT, and continuation of her home medication metoprolol. SCAD is a rare etiology of ACS with a predilection for young to middle-aged females. In the United States, SCAD has an approximate yearly incidence of 3.4% in females. The coronary vessels affected more frequently are the LAD and the RAC with 57% and 29% rate of dissection respectively. SCAD was noted to have a recurrence rate of 11% within 2-3 years with an increased recurrence rate of 29% at the 10-year follow-up. While the reasons for recurrence are unclear, there is a clear association between vessel tortuosity and HTN with higher rates of recurrence. A previous study reported that beta-blockers can reduce the risk of recurrence by almost two-thirds. The decreased risk was attributed to the mechanism of action of beta-blockers: decreasing intracoronary shear stress, decreasing heart contractility, and reducing aneurysm degeneration. Our patient suffered a recurrent case of SCAD despite recommended treatment with a beta-blocker. Further research is needed to risk-stratify patients and to clarify if a specific dose or type of beta-blocker will protect against SCAD recurrence.