Β-blockers In Patients Research Articles

Microarray analysis demonstrates up-regulation of the endothelin-1 gene with compensatory down-regulation of the ETA receptor gene in human portal vein.

High blood pressure in the portal vein, portal hypertension (PH), is the final common pathway in liver cirrhosis regardless of aetiology. Complications from PH are the major cause of morbidity and mortality in these patients. Current drug therapy to reduce portal pressure is mainly limited to β-adrenergic receptor blockade but approximately 40% of patients do not respond. Our aim was to use microarray to measure the expression of ∼20,800 genes in portal vein from patients with PH undergoing transplantation for liver cirrhosis (PH, n=12) versus healthy vessels (control, n=9) to identify potential drug targets to improve therapy. Expression of 9,964 genes above background was detected in portal vein samples. Comparing PH veins versus control (adjusted P-value < 0.05, fold change > 1.5) identified 548 up-regulated genes and 1,996 down-regulated genes. The 2,544 differentially expressed genes were subjected to pathway analysis. We identified 49 significantly enriched pathways. The endothelin pathway was ranked the tenth most significant, the only vasoconstrictive pathway to be identified. ET-1 gene (EDN1) was significantly up-regulated, consistent with elevated levels of ET-1 peptide previously measured in PH and cirrhosis. ETA receptor gene (EDNRA) was significantly down-regulated, consistent with an adaptive response to increased peptide levels in the portal vein but there was no change in the ETB gene (EDNRB). The results provide further support for evaluating the efficacy of ETA receptor antagonists as a potential therapy in addition to β-blockers in patients with PH and cirrhosis.

β-Blocker Use and Clinical Outcomes in Patients With COPD Following Acute Myocardial Infarction

While β-blockers are associated with decreased mortality in cardiovascular disease (CVD), exacerbation-prone patients with chronic obstructive pulmonary disease (COPD) who received metoprolol in the Beta-Blockers for the Prevention of Acute Exacerbations of Chronic Obstructive Pulmonary Disease (BLOCK-COPD) trial experienced increased risk of exacerbations requiring hospitalization. However, the study excluded individuals with established indications for the drug, raising questions about the overall risk and benefit in patients with COPD following acute myocardial infarction (AMI). To investigate whether β-blocker prescription at hospital discharge is associated with increased risk of mortality or adverse cardiopulmonary outcomes in patients with COPD and AMI. This prospective, longitudinal cohort study with 6 months of follow-up enrolled patients aged 35 years or older with COPD who underwent cardiac catheterization for AMI at 18 BLOCK-COPD network hospitals in the US from June 2020 through May 2022. Prescription for any β-blocker at hospital discharge. The primary outcome was time to the composite outcome of death or all-cause hospitalization or revascularization. Secondary outcomes included death, hospitalization, or revascularization for CVD events, death or hospitalization for COPD or respiratory events, and treatment for COPD exacerbations. Among 3531 patients who underwent cardiac catheterization for AMI, prevalence of COPD was 17.1% (95% CI, 15.8%-18.4%). Of 579 total patients with COPD and AMI, 502 (86.7%) were prescribed a β-blocker at discharge. Among the 562 patients with COPD included in the final analysis, median age was 70.0 years (range, 38.0-94.0 years) and 329 (58.5%) were male; 553 of the 579 patients (95.5%) had follow-up information. Among those discharged with β-blockers, there was no increased risk of the primary end point of all-cause mortality, revascularization, or hospitalization (hazard ratio [HR], 1.01; 95% CI, 0.66-1.54; P = .96) or of cardiovascular events (HR, 1.11; 95% CI, 0.65-1.92; P = .69), COPD-related or respiratory events (HR, 0.75; 95% CI, 0.34-1.66; P = .48), or treatment for COPD exacerbations (rate ratio, 1.01; 95% CI, 0.53-1.91; P = .98). In this cohort study, β-blocker prescription at hospital discharge was not associated with increased risk of adverse outcomes in patients with COPD and AMI. These findings support use of β-blockers in patients with COPD and recent AMI.

β-blockers may be detrimental in frail patients with heart failure with preserved ejection fraction.

The effectiveness of β-blocker in patients with heart failure with preserved ejection fraction (HFpEF) remains to be determined. We aimed to clarify the association between the use of β-blocker and prognosis according to the status of frailty. We compared prognosis between HFpEF patients with and without β-blockers stratified with the Clinical Frailty Scale (CFS), using data from the PURSUIT-HFpEF registry (UMIN000021831). Among 1159 patients enrolled in the analysis (median age, 81.4years; male, 44.7%), 580 patients were CFS ≤ 3, while 579 were CFS ≥ 4. Use of β-blockers was associated with a worse composite endpoint of all-cause death and heart failure readmission in patients with CFS ≥ 4 (adjusted hazard ratio (HR) 1.43, 95% CI 1.10-1.85, p = 0.007), but was not significantly associated with this endpoint in those with CFS ≤ 3 (adjusted HR 0.95, 95% CI 0.71-1.26, p = 0.719) in multivariable Cox proportional hazard models. These results were confirmed in a propensity-matched analysis (HR in those with CFS ≥ 4: 1.42, 95% CI 1.05-1.90, p = 0.020; that in those with CFS ≤ 3: 0.83, 95% CI 0.60-1.14, p = 0.249), and in an analysis in which patients were divided into CFS ≤ 4 and CFS ≥ 5. Use of β-blockers was significantly associated with worse prognosis specifically in patients with HFpEF and high CFS, but not in those with low CFS. Use of β-blockers in HFpEF patients with frailty may need careful attention.

Things We Do for No Reason™: Discontinuing β-blockers in patients who use cocaine.

Things We Do for No Reason™: Discontinuing β-blockers in patients who use cocaine.

Arg389Gly beta-1-adrenergic receptor polymorphism determines neutrophil-stunning-associated cardioprotection by metoprolol

Abstract Background Cardioprotective strategies to limit infarct size (IS) have become crucial. The damaged inflicted on the myocardium is the result of the processes of Ischemia and Reperfusion (I/R). In the clinical trial METOCARD-CNIC, it was shown that the intravenous (i.v.) pre-reperfusion administration of the β1-selective antagonist metoprolol reduces IS and improves long-term cardiac function in patients after acute myocardial infarction (1). However, the small sample size precludes a definite conclusion. Despite not having demonstrated a solid clinical benefit in terms of hard endpoints reduction, the clinical guidelines for the management of ST-Elevation Myocardial Infarction (STEMI) recommend the early administration of i.v. β-blockers in patients undergoing Primary Coronary Intervention. Additionally, our group has recently described that the beneficial effect of metoprolol against myocardial I/R injury is due to neutrophil stunning (2), which represents a one-of-a-kind property not shared by other i.v. β-blockers, such as atenolol or propranolol (3). Purpose Since β1-adrenergic receptor (ADRB1) is one of major targets of pharmacological therapy, great efforts are now underway to account for the relevance of the polymorphic variation. Here we explore whether the cardioprotection exerted by metoprolol is dependent on genetic polymorphisms in human ADRB1. Methods Patients included in the METOCARD-CNIC trial were grouped into the different variants for the ADRB1, rs1801252 and rs1801253 (SerGly49 and Arg389Gly, respectively), which might affect their response to the beta-1 modulation exerted by metoprolol on neutrophils and thus its cardioprotective effect. Additionally, the polymorphic-dependent effect of metoprolol on neutrophil migration was evaluated in healthy volunteers, whose neutrophils were exposed across the transwell filter to the CXCL1 in the presence or absence of metoprolol. Drug-receptor interaction properties were evaluated in silico. Results We found that Arg389Gly polymorphism of the human ADRB1 impacts the cardioprotective effect of metoprolol in STEMI patients. Therefore, Arg389 homozygosity was associated with lower infarcts (Figure 1) and better long-term left ventricle ejection fraction when metoprolol was intravenously administered prior reperfusion. Moreover, the disrupting effect of metoprolol on neutrophil migration was only observed in Arg389 homozygote volunteers (Figure 2). These differences were attributed to alterations in the drug-receptor complex stability when Gly residues are present in position 389 of the ADRB1. Conclusions From our perspective, these results are the first showing a polymorphic implication in drug response against myocardial I/R injury. All the data presented refine cardiovascular pharmacotherapy, and have major implications for the prospective clinical trial design aiming at positioning metoprolol as the beta-blocker of choice to reduce hard endpoints in STEMI patients.CardioprotectionNeutrophil migration

β-Blockers in Patients With Sepsis

β-Blockers in Patients With Sepsis

Flecainide is associated with a reduction in arrhythmic events in a large cohort of patients with catecholaminergic polymorphic ventricular tachycardia

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): This work was supported by the ZonMW Priority Medicines for Rare Diseases and Orphan Drugs (grant 113304045 to Dr Van der Werf) and the Netherlands CardioVascular Research Initiative: the Dutch Heart Foundation, Dutch Federation of University Medical Centres, the Netherlands Organisation for Health Research and Development and the Royal Netherlands Academy of Sciences (PREDICT2 to Dr. Wilde). Background In patients with catecholaminergic polymorphic ventricular tachycardia (CPVT), β-blocker may be insufficiently protective. A randomized clinical trial showed that flecainide reduces ventricular arrhythmias (VAs) in CPVT and small retrospective cohort studies suggest that this translates into a reduction of arrhythmic events. Objective To evaluate the efficacy of flecainide when added to β-blockers for the prevention of arrhythmic events (AE) in a large cohort of patients with CPVT using paired analysis. Methods From two international registries, this multicentre retrospective cohort study included patients with a clinical and/or genetic diagnosis of CPVT using flecainide as an adjunct to β-blockers. The study period, which comprised a pre- and on-flecianide period, was defined as the period in which background therapy, i.e. β-blocker type (β1-selective or nonselective), left cardiac sympathetic denervation (LCSD), and implantable cardioverter-defibrillator (ICD) treatment status, remained unchanged within individual patients. The primary endpoint was AEs, defined as SCD, sudden cardiac arrest (SCA), appropriate ICD shock, and arrhythmic syncope. The effect of flecainide on AE rates was assessed using a generalized linear mixed model assuming Poisson distribution and random effects for patients. Results Two-hundred forty-seven patients (median age at start of flecainide 18 years [IQR 14-29], 123 [50%] female, median flecainide dose 2.2 mg/kg/day [IQR 1.7-3.1]) were included. At baseline, 70 (28%) patients had an ICD and 21 (9%) had a LCSD performed. Nonselective β-blockers were used by 133 (54%) patients. During a median pre-flecainide follow-up of 2.1 years (IQR 0.4-7.2), 41 patients experienced 58 AEs. During a median on-flecainide follow-up of 2.9 years (IQR 1.0-6.0), 23 patients experienced 38 AEs. There was a significant reduction in AEs after initiation of flecainide (OR 0.55 [0.38-0.83]; p=0.007). Among patients who were symptomatic before diagnosis or before the initiation of flecainide (n=167), flecainide was associated with a significant reduction in AEs (OR 0.49 [0.31-0.77]; p=0.002). Among patients with ≥1 AE on β-blocker therapy (n=41), adding flecainide was associated with a significant reduction in AEs (OR 0.25 [0.14-0.45]; p&amp;lt;0.001). Conclusion Flecainide was associated with a reduction in AEs when added to β-blockers in patients with CPVT in the overall cohort, symptomatic patients, and particularly in patients with breakthrough AEs on β-blocker therapy.

Beta-blockers used in cardiac failure and blood glucose level impairment - a literature review

Introduction: Blood sugar level impairment, especially diabetes mellitus (DM) is a significant problem. DM leads to many serious complications. Patients suffering from cardiac failure (HF) and diabetes have a risk of hospitalization increased 1.5 times compared to the control group without DM. That is why it is very important to keep appropriate glycemic control. β-blockers, are considered to cause a blood glucose level impairment. The relationship between the use of β-blockers and the development of DM is one of the most interesting and controversial issues in diabetology. Despite many benefits, some doctors are reluctant to prescribe β-blockers because of perceived negative metabolic effects.Aim of study: The purpose of the study was to review the literature describing oral β-blockers, used in HF, influence on glucose metabolism and to discover the best β-blocker treatment for cardiac failured diabetics and prediabetics.&#x0D; Methods: A systemic review was conducted using PubMed, ScienceDirect, Google Scholar databases. The search strategy was based on the following terms: beta-blocker, blood glucose level, metoprolol, nebivolol, carvedilol, bisoprolol.&#x0D; Results: β-blockers differ in terms of their mechanism of action and their effects on glucose metabolism. Metoprolol is associated with a worsening of glucose and lipid control. Bisoprolol have a neutral impact on glucose metabolism. Vasodilating β-blockers may improve glycemic profile.Conclusions: All four β-blockers used in HF have similar blood pressure lowering effect but different metabolic effect. Metoprolol should not be used as a drug of choice in patients with impaired glucose metabolism. Bisoprolol, nebivolol or carvedilol may be recommended as a drug of choice in patients with cardiac failure and impaired carbohydrate metabolism. The choice between bisoprolol and vasodilating β-blockers in patients with glycemic disorders is still an unresolved issue.

Effectiveness of beta-blockers in the therapy of arterial hypertension

Recently, the interest of the cardiology community has been focused on the results of the latest studies on the use of vasodilating β-blockers in patients with arterial hypertension. A review of these studies demonstrates a number of advantages over conventional cardioselective drugs (without vasodilator properties). The positive features of vasodilating β-adrenoblockers are proven metabolic neutrality, proportional reduction of central and peripheral blood pressure, minimal effect on bronchial patency, the absence of negative effect on erectile function, reduction in the frequency of cardiovascular complications in patients with arterial hypertension.

Physician Perspectives on the Use of Beta Blockers in Heart Failure With Preserved Ejection Fraction

β-blockers are commonly used in heart failure with preserved ejection fraction (HFpEF), even in the absence of a compelling indication and despite the potential to cause harm. Identifying reasons for β-blocker prescription in HFpEF could permit the development of strategies to reduce unnecessary use and potentially improve medication prescribing patterns in this vulnerable population. We administered an online survey regarding β-blocker prescribing behavior to physicians trained in internal medicine or geriatrics (noncardiology physicians) and to cardiologists at 2 large academic medical centers. The survey assessed the reasons for β-blocker initiation, agreement regarding initiation and/or continuation of β-blockers by another clinician, and deprescribing behavior. The response rate was 28.2% (n=231). Among respondents, 68.2% reported initiating β-blockers in patients with HFpEF. The most common reason for initiating a β-blocker was for treatment of an atrial arrhythmia. Notably, 23.7% of physicians reported initiating a β-blocker without an evidence-based indication. When a β-blocker was considered not necessary, 40.1% of physicians reported they were rarely or never willing to deprescribe. The most common reason for not deprescribing a β-blocker when the physician felt that a β-blocker was unnecessary was the concern about interfering with another physicians' treatment plan (76.6%). In conclusion, a significant proportion of noncardiology physicians and cardiologists report prescribing β-blockers to patients with HFpEF, even when evidence-based indications are absent, and rarely deprescribe β-blockers in these scenarios.

β-Blockers could improve the 28-day and 3-year survival of patients with end-stage renal disease: a retrospective cohort study.

Dialysis or non-dialysis end-stage renal disease (ESRD) patients are accompanied by cardiovascular disease (CVD) or hypertension. We aimed to study the effect of a common treatment for CVD, β-blockers, on the survival of ESRD patients, improving their prognosis from the perspective of drug therapy. It was a retrospective cohort study using the Medical Information Mart for Intensive Care dataset. ESRD patients in the intensive care unit from June 2001 to October 2012 were included. We examined the effect of using versus not using β-blockers in the overall population and subgroups with the risk of 28-day and 3-year mortality through Cox proportional hazards models and Kaplan-Meier curves. A total of 1639 participants were included with 371 (22.64%) β-blockers users. There were 315 (19.22%) 28-day and 970 (59.18%) 3-year mortality events during follow-up. Using β-blockers in overall ESRD patients could reduce all-cause 28-day mortality [adjusted hazard ratio (HR) 0.450, 95% confidence interval (CI) 0.325-0.624] and 3-year mortality (adjusted HR 0.695, 95% CI 0.589-0.821). This result was consistent among subgroups (ESRD without hypertension: adjusted HR 0.412, 95% CI 0.289-0.588; with CVD: adjusted HR 0.478, 95% CI 0.321-0.711; without CVD: adjusted HR 0.448, 95% CI 0.248-0.810; with dialysis: adjusted HR 0.471, 95% CI 0.320-0.694) in 28-day mortality, and the 3-year mortality was consistent. In ESRD patients with hypertension and without dialysis subgroups, β-blockers had no effect on survival. Using β-blockers could reduce the risk of 28-day and 3-year mortality in ESRD patients, including those with CVD. This study provided a reference for the treatment of β-blockers in patients with ESRD.

Alteration of immune status during treatment with β-blockers in patients with essential hypertension

The balance of cytokines (IL-2, IL-10, IF-γ) in patients with essential hypertension beforeandaftertreatmentwithβ-blockerswasstudied.20patientsaged45-65yearsbefore and after treatment with β-blockers was studied. 20 patients aged 45-65 years anddiagnosedwithessentialhypertension(12women,8men)wereinvestigated.Forand diagnosed with essential hypertension (12 women, 8 men) were investigated. For thetreatmentofhypertension,patientsreceivedsecond-generationbeta-selectivethe treatment of hypertension, patients received second-generation beta-selective β-blockersEgilokandBetalokZok,andthird-generationβ-blockerNebiletforoneβ-blockers Egilok and Betalok Zok, and third-generation β-blocker Nebilet for one month.Patientsperformedtheirbloodpressuremeasurementsdailyinthemorningmonth. Patients performed their blood pressure measurements daily in the morning duringImonth.Thecontentofinterleukins(IL-2,IL-10,IF-γ)inthebloodbytheduring I month. The content of interleukins (IL-2, IL-10, IF-γ) in the blood by the immuneenzymaticELISAmethodonasemi-automaticreaderStatFax3200withimmune enzymatic ELISA method on a semi-automatic reader Stat Fax 3200 with RayBio,(USA)reagentwasmeasured.TheresultsofourstudiesshowanincreaseRayBio, (USA) reagent was measured. The results of our studies show an increase inthelevelofCD4+(IL-2)cytokinesinthebloodofthestudiedhypertensivein the level of CD4+ (IL-2) cytokines in the blood of the studied hypertensive patients,whichcoincideswiththeliteraturedataontheimportantroleofCD4+patients, which coincides with the literature data on the important role of CD4+ pro-inflammatorycytokinesinthepathogenesisofhypertension.After1monthofpro-infl ammatory cytokines in the pathogenesis of hypertension. After 1 month of treatmentwithβ-blockers,thepatient’sarterialpressureandIL-2levelcontentintreatment with β-blockers, the patient’s arterial pressure and IL-2 level content in theblooddecreased.Thesedataindicatetheimportantroleofinflammationinthethe blood decreased. These data indicate the important role of infl ammation in the pathogenesisofhypertensionandtheanti-inflammatoryeffectsofβ-brokers,usedpathogenesis of hypertension and the anti-infl ammatory effects of β-brokers, used inthetreatmentofhypertension.in the treatment of hypertension

Cardiovascular Drug Use After Acute Kidney Injury Among Hospitalized Patients With a History of Myocardial Infarction

Patients who survive acute kidney injury (AKI) may receive fewer cardioprotective drugs. Our objective was to measure the difference in time to dispensing of evidence-based cardiovascular drugs in patients with a history of myocardial infarction (MI) with and without AKI. This was a population-based cohort study of patients 66 years of age and older with a history of MI who survived a hospitalization complicated with AKI, propensity-score matched to patients without AKI. The primary outcome was time to outpatient dispensing of an angiotensin-converting enzyme inhibitor (ACEi)/angiotensin II receptor blocker (ARB), statin, or β-blocker within 1 year of hospital discharge. We identified 28,871 patients with AKI, of whom 21,452 were matched 1:1 to patients without AKI. In the matched cohort, mean age was 80 years, 40% were female, and 34% had an MI during the index hospitalization. AKI was associated with less frequent dispensing of all 3 cardiovascular drug classes within 1 year of hospital discharge (subdistribution hazard ratio [sHR], 0.93; 95% confidence interval [CI], 0.91-0.95). This association was most pronounced in patients with stage 2 (sHR, 0.81; 95% CI, 0.75-0.88) and stage 3 (sHR, 0.71; 95% CI, 0.64-0.79) AKI. We observed less frequent dispensing of statins in patients with stage 2 (sHR, 0.87; 95% CI, 0.81-0.92) and stage 3 (sHR, 0.85; 95% CI, 0.78-0.93) AKI and less frequent dispensing of β-blockers in patients with stage 3 AKI (sHR, 0.86; 95% CI, 0.79-0.94). In patients with a history of MI, survivors of AKI were less likely to receive prescriptions for ACEi/ARB, statins, or β-blockers within 1 year of hospital discharge. This association was most pronounced in patients with stages 2 and 3 AKI.

Prognostic impact of guideline-directed medical therapy in patients with heart failure on regular hemodialysis

BackgroundRenin-angiotensin system inhibitor (RASi) and β-blocker provide prognostic benefits as guideline-directed medical therapy (GDMT) in patients with heart failure and reduced ejection fraction (HFrEF). However, there is limited data for the favorable effects in such patients receiving regular hemodialysis. We aimed to evaluate the prognostic impact of RASi and β-blocker in patients with HFrEF who receive regular hemodialysis. MethodsIn this retrospective, single-center, observational study, from 2110 consecutive patients hospitalized for HF and who survived to discharge, 97 with HFrEF who received regular hemodialysis were included for analysis. They were classified into three groups according to prescribed medication at discharge following index hospitalization: both RASi and β-blocker (Dual-GDMT group: n = 55), either RASi or β-blocker (Mono-GDMT group: n = 34), and neither RASi nor β-blocker (No-GDMT group: n = 8). The primary endpoint was a composite of all-cause death and rehospitalization for heart failure. ResultsThe mean age was 66 years and 79% of the patients were men. During the median follow-up of 501 days, the primary endpoint occurred in 43 patients (44%). Kaplan-Meier analysis revealed that the Dual-GDMT group had the lowest rates of the primary endpoint (log-rank test for trend: p < 0.001). Even after adjustment for diverse covariates (multivariate Cox regression), the Dual-GDMT (hazard ratio [HR]: 0.04, 95% confidence interval (CI): 0.005–0.32) and Mono-GDMT (HR: 0.08, 95% CI: 0.01–0.50) groups had better prognoses than the No-GDMT group. ConclusionsThe prescription of RASi and/or β-blocker was associated with a lower adverse-event rate after discharge in patients with HFrEF who were on regular hemodialysis.

Associations between β-Blocker Therapy at Discharge and Long-Term Follow-Up Outcomes in Patients with Unstable Angina Pectoris.

Background The effects of β-blockers in patients with unstable angina pectoris (UAP) are unclear. We tried to evaluate associations between β-blockers in UAP and long-term outcomes. Methods We enrolled 5591 UAP patients and divided them into 2 groups based on β-blockers at discharge: 3790 did β-blockers and 1801 did not used them. Propensity score matching at 1 : 1 was performed to select 1786 patients from each group. The primary endpoint was major adverse cardiac and cerebral events (MACCE) during the long-term follow-up period. Results 67.8% of patients were on β-blockers at discharge; these patients were more likely to have CHD risk factors, lower ejection fraction, and severity of the coronary artery lesions. Over a median of 25.0 years, the incidence of MACCE was 25.5%. The risk was not significantly different between those on and those not on β-blocker treatment. The multivariate Cox regression analysis showed that no β-blocker use at discharge was not an independent risk factor for MACCE and sequence secondary endpoints. After propensity score matching, the results were similar. Conclusions β-blocker use was not associated with lower MACCE and other secondary composite endpoints in long-term outcomes. This result adds to the increasing body of evidence that the routine prescription of β-blockers might not be indicated in patients with UAP. Trial registration had retrospectively registered.

Beta-blocker use and urothelial bladder cancer survival: a Swedish register-based cohort study

Background Recent observational studies linked β-adrenergic receptor blocker use with improved survival in patients with several cancer types, but there is no information on the potential effects of β-blockers in patients with bladder cancer. Literature from pre-clinical studies is also limited, but urothelial cancer can exhibit significant overexpression of β-adrenergic receptors relative to normal urothelial tissue, suggesting that urothelial cancer may benefit from β-blockade therapy. We thus aimed to explore the possible association between β-blocker use and bladder cancer-specific mortality (BCSM) among patients with urothelial bladder cancer. Material and methods Patients diagnosed during 2006–2014 and identified from the Swedish Cancer Register (n = 16,669) were followed until 31 December 2015. Cox regression was used to evaluate the association of β-blockers dispensed within 90 days prior to cancer diagnosis with BCSM (primary outcome) and all-cause mortality, while controlling for socio-demographic factors, tumor characteristics, comorbidity, other medications and surgical procedures. Hazard ratios (HR) with 95% confidence intervals (CI) were reported. Results Overall, β-blocker use was associated with lower BCSM [HR 0.88 (95%CI 0.81–0.96)]. Especially use of nonselective β-blockers showed a clear inverse association in comparison with both nonuse [0.66 (0.50–0.86)] and use of other antihypertensive medications [0.72 (0.54–0.95)]. The inverse association was most pronounced among patients with locally advanced/metastatic disease: [0.35 (0.18–0.68)]. A lower-magnitude inverse association was observed for selective β-blocker use [0.91 (0.83–0.99)]. Largely similar inverse associations were observed for hydrophilic [0.82 (0.70–0.95)] and lipophilic [0.91 (0.83–1.00)] β-blocker use. Conclusion β-blocker use, particularly of the nonselective type, was associated with lower BCSM, especially in patients with locally advanced/metastatic urothelial bladder cancer.

Levosimendan as a "Bridge to Optimization" in Patients with Advanced Heart Failure with Reduced Ejection-A Single-Center Study.

Background: Patients with advanced heart failure with reduced ejection fraction often cannot tolerate target doses of guideline-directed medical therapy due to symptomatic hypotension, renal dysfunction, and associated electrolyte abnormalities. While levosimendan can facilitate the titration of β-blockers in patients with advanced HFrEF, it is unclear whether ambulatory levosimendan infusions would offer the same benefit. In this prospective study, we investigate the effects of intermittent ambulatory levosimendan infusions on the uptitration of disease-modifying drugs. Methods: We enrolled 37 patients with advanced HFrEF who received repeated ambulatory infusions of levosimendan between January 2018 and January 2021. The demographic, clinical, and laboratory data were acquired 24 h before the first and the last ambulatory levosimendan infusion. Results: At the 1 year follow-up, the enrolled patients were on significantly higher doses of guideline-directed medical therapy, including bisoprolol (3.2 ± 2.8 mg vs. 5.9 ± 4.1 mg; p = 0.02), sacubitril/valsartan (41.67 ± 32.48 mg vs. 68.5 ± 35.72 mg; p = 0.01), and eplerenone (12.7 ± 8.5 mg vs. 22.8 ± 13.6 mg; p = 0.03). Furthermore, a substantial decrease in the furosemide dose was observed (123.2 ± 32.48 mg vs. 81.6 ± 19.47 mg; p < 0.0001). Conclusions: Levosimendan facilitates the optimization of disease-modifying heart failure medications in previously intolerant advanced HFrEF patients.

Avoidance of β-blockers in patients who use stimulants is not supported by good evidence.

KEY POINTS Physicians often hesitate to prescribe β-blocker therapy for patients who actively use stimulants, even for indications such as heart failure with reduced ejection fraction and tachyarrhythmias, worrying that potentially harmful interactions will outweigh well-established benefits.[1][1

Періопераційне застосування β-адреноблокаторів у пацієнтів високого ризику

Незважаючи на краще розуміння того, які бувають передвісники розвитку хронічної серцевої недостатності та які сигнальні системи лежать в основі її патофізіології, а також покращення результатів терапії, значна кількість пацієнтів, особливо похилого віку, не отримують ефективного лікування. Пацієнти похилого віку з такою патологією зазвичай вимагають додаткового об’єму діагностики й значного розширення спектра анестезіологічних заходів у відділеннях інтенсивної терапії. Анестезіологи мають потребу в удосконаленні періопераційного знеболювання при проведенні оперативних втручань. Препарати групи β-адреноблокаторів для лікування пері­операційної гіпертензії, ішемії й аритмій призначаються в передопераційному періоді в групі пацієнтів, які раніше не отримували такого лікування. Періопераційне призначення β-адреноблокаторів у пацієнтів високого ризику використовується недостатньо. Проте питання про те, чи мають β-адреноблокатори знову застосовуватись у передопераційному періоді виключно для запобігання негативним наслідкам хронічної серцевої недостатності, залишається вельми дискутабельним.

Beta-blocker could show the prognostic impact in heart failure patients even on the regular hemodialysis

Abstract Background β-blockers are recommended as standard medications for patients with heart failure (HF) and reduced left ventricular ejection fraction (LVEF). However, this favorable prognostic effect of β-blockers has not been fully validated in patients receiving regular hemodialysis. Indeed, prior clinical trials have generally excluded such very high-risk population for adverse cardiovascular events. Main reasons for that are the limited number of regular hemodialysis patients in the Western nations, and too high rates of clinical events. Purpose This study aimed to clarify the prognostic benefit of β-blocker in patients on regular hemodialysis who were hospitalized due to HF. Methods This observational study included 1,930 consecutive patients who were hospitalized for worsening of HF and discharged alive from 2013 to 2019. Of them, 151 patients who underwent regular hemodialysis were ultimately analyzed. They were divided into 2 groups depending on the prescription of β-blocker at the discharge; β-blocker group (n=115) and No-β-blocker group (n=36). The primary endpoint of this study was a composite of death from any cause and rehospitalization due to HF. Results During the observation period with 501 days of median follow-up (IQR: 197–954 days), the primary endpoint was occurred in 45 patients (39%) who were receiving β-blockers, while in 24 patients (67%) who were not. Kaplan-Meier analysis showed a significantly lower rate of the primary endpoint in patients in the β-blocker group (Log-rank, p&amp;lt;0.001, Figure). After the adjustment for age, sex, LVEF, systolic blood pressure, heart rate and atrial fibrillation, the administration of β-blocker was still an independent predictor for the primary endpoint in patients who underwent regular hemodialysis (hazard ratio; 0.46, 95% confidence interval; 0.26–0.82). Further analysis each for the population with reduced LVEF (&amp;lt;45%) and preserved LVEF (&amp;gt;45%) showed that the main result of the current study was consistent with that in the reduced LVEF group (Log-rank, p=0.005), but was diminished in the preserved LVEF group (p=0.13). Conclusion The prescription of β-blocker at discharge in HF patients with regular hemodialysis was associated with lower risk of adverse cardiovascular events, mainly in the patients with reduced LVEF. From the findings of our study, we should consider the administration of β-blockers in HF patients, even they are on the regular hemodialysis. Funding Acknowledgement Type of funding sources: None. Figure 1