Safety of beta-blocker discontinuation after acute coronary syndromes with preserved or mildly reduced left ventricular ejection fraction: a target trial emulation from a real-world cohort.

AIMS: The benefit of long-term beta-blocker therapy after acute coronary syndromes (ACS) without heart failure in the reperfusion era is uncertain. Two recent randomized trials found conflicting results. The present study assessed the safety of beta-blocker discontinuation within 12 months following ACS with LVEF ≥40%. METHODS: In a multicentre prospective real-world cohort (N=3,762) of patients hospitalized for ACS, patients with LVEF ≥40% and beta-blockers at discharge were included. Patients who continued beta-blockers at one year were compared with those who discontinued beta-blockers within 12 months post-ACS using target trial emulation and inverse probability weighting over an additional four-year follow-up. The primary endpoint was major adverse cardiovascular events (MACE), a composite of four-year cardiovascular death, myocardial infarction, stroke, transient ischemic attack, unplanned coronary revascularization, or unstable angina hospitalization. RESULTS: Of 2,077 patients, 1,758 (85%) continued beta-blockers and 319 (15%) had discontinued beta-blockers at one year. The risk of primary endpoint was similar in both groups (14.1% versus 14.3% with beta-blocker discontinuation versus continuation; adjusted hazard ratio [aHR]=0.98; 95% confidence interval, 0.72-1.34, P=0.91). Subgroup analysis suggested a higher risk of primary endpoint with beta-blocker discontinuation after STEMI (aHR=1.46 [0.99-2.16]) compared to NSTEMI (aHR=0.70 [0.40-1.22], Pinteraction=0.033), whereas there was no interaction with LVEF (Pinteraction=0.68). CONCLUSIONS: Beta-blocker discontinuation within 12 months following ACS with LVEF ≥40% was not associated with an increased risk of MACE compared to long-term beta-blocker therapy. Subgroup analysis suggested potential risk in STEMI patients. Discontinuing beta-blockers 12 months after ACS appears safe in patients with LVEF ≥40%, particularly after NSTEMI.

Beta-blockers are part of the standard drug therapy prescribed to prevent adverse health events in patients who suffered from myocardial infarction. However, the studies that established their benefit were conducted before the advent of modern therapies, that have since then dramatically changed the prognosis. The benefit of long-term beta-blockers in the contemporary era has therefore been questioned. The present study assessed the safety of beta-blocker discontinuation within 12 months after myocardial infarction in patients who did not have severely impaired heart function. Beta-blocker discontinuation within 12 months after myocardial infarction was safe, as it was not associated with a higher risk of major adverse cardiovascular events or death, compared to long-term beta-blocker continuation. Patients who presented with acute occlusion of a coronary artery ­ a severe type of myocardial infarction referred to as "ST-elevation myocardial infarction" ­ may still benefit from long-term beta-blocker therapy based on subgroup analysis.

Betablockers and clinical outcome after surgical aortic valve replacement: a report from the SWEDEHEART registry.

OBJECTIVES: Previous reports suggest that betablockers appear non-beneficial after surgical aortic valve replacement (SAVR). This study aims to clarify the associations between betablockers and long-term outcome after SAVR. METHODS: All patients with isolated SAVR due to aortic stenosis in Sweden between 2006 and 2020, alive at 6 months after surgery, were included. Patients were identified in the SWEDEHEART registry, and records were merged with data from 3 other mandatory national registries. Association between dispensed betablockers and major adverse cardiovascular events (MACE) (all-cause mortality, myocardial infarction and stroke) was analyzed using Cox proportional hazards models, with time-updated data on medication and adjusted for age, sex and comorbidities at baseline. RESULTS: In total, 11 849 patients were included [median follow-up 5.4 years (range 0-13.5)]. Betablockers were prescribed to 79.7% of patients at baseline, decreasing to 62.2% after 5 years. Continuing treatment was associated with higher risk of MACE [adjusted hazard ratio 1.14 (95% confidence interval, CI 1.05-1.23)]. The association was consistent over subgroups based on age, sex and comorbidities except atrial fibrillation [hazard ratio (HR) 1.05 (95% CI 0.93-1.19)]. A sensitivity analysis including time-updated data on comorbidites attenuated the difference between the groups [HR 1.04 (95% CI 0.95-1.14, P = 0.33)]. CONCLUSIONS: Treatment with betablockers did not appear to be associated with inferior long-term outcome after SAVR, when adjusting for new concomitant diseases. Thus, it is likely that it is the underlying cardiac diseases that are associated with MACE rather than betablocker treatment.

The negative chronotropic effects of (±)-propranolol and (±)-4-NO2-propranolol in the rat isolated right atrium are due to blockade of the 6-nitrodopamine receptor.

The positive chronotropic action induced by 6-nitrodopamine (6-ND) is selectively blocked by ß1-adrenoceptor antagonists at concentrations that do not affect the positive chronotropic effect induced by dopamine, noradrenaline, and adrenaline. Here, the effects of ( ±)-propranolol, ( ±)-4-NO2-propranolol, and ( ±)-7-NO2-propranolol were investigated in the rat isolated right atrium. The atrium was mounted in glass chambers containing gassed (95%O2:5%CO2) and warmed (37 °C) Krebs-Henseleit's solution, and the isometric tension registered (PowerLab system). ( ±)-Propranolol, ( ±)-4-NO2-propranolol, and ( ±)-7-NO2-propranolol caused concentration-dependent falls in the spontaneous atrial frequency (pIC50: 4.80 ± 0.10, 4.64 ± 0.10, and 4.95 ± 0.10, respectively). The calculated pA2 values for ( ±)-propranolol, ( ±)-4-NO2-propranolol, and ( ±)-7-NO2-propranol on noradrenaline-induced positive chronotropism were 8.44 ± 0.08, 6.41 ± 0.07, and 9.21 ± 0.29, respectively. The positive chronotropism induced by 6-ND (10 pM) was blocked by ( ±)-propranolol (1 µM) and ( ±)-4-NO2-propranolol (30 nM), whereas ( ±)-7-NO2-propranolol (1 µM) had no effect on 6-ND-induced responses. The pIC50 of ( ±)-propranolol, ( ±)-4-NO2-propranolol, and ( ±)-7-NO2-propranolol were significantly shifted to the right in L-NAME-treated atria. The discrepancy between pA2 values of ( ±)-propranolol and its respective pIC50 indicates that the falls in atrial rate induced by ( ±)-propranolol should not be attributed to b-adrenergic antagonism. The reduced chronotropism by ( ±)-propranolol was unaffected by the sodium channel inhibitors tetrodotoxin and lidocaine but that was abolished in atria pre-treated with ( ±)-4-NO2-propranolol. The finding that ( ±)-propranolol reduces spontaneous atrial rate only in concentrations that affect 6-ND-induced positive chronotropism confirms the role of this catecholamine as an endogenous modulator of heart chronotropism. ( ±)-4-NO2-Propranolol behaves as a selective antagonist of 6-ND in the rat isolated atrium.

Short- and long-term effects of beta-blockers on symptoms of anxiety and depression in patients with myocardial infarction and preserved left ventricular function: a pre-specified quality of life sub-study from the REDUCE-AMI trial.

AIMS: Among patients with myocardial infarction (MI) with preserved left ventricular ejection fraction (LVEF), the REDUCE-AMI trial did not demonstrate a benefit of beta-blocker vs. no beta-blocker treatment on all-cause mortality and recurrent myocardial infarction. The aim of this pre-specified sub-study was to investigate effects of beta-blockers on self-reported symptoms of anxiety and depression. METHODS AND RESULTS: In this parallel-group, open-label, registry-based randomized trial, assessments with the Hospital Anxiety and Depression Scale were obtained at hospitalization and two follow-up points (6-10 weeks and 12-14 months) after MI. Analyses were based on the intention-to-treat principle using linear mixed models, calculating both short- and long-term effects. From August 2018 through June 2022, 806 patients were enrolled. At baseline, 27% of patients were possible cases of anxiety (m, 5.6; SD, 3.9) and 14% were possible cases of depression (m, 3.9; SD, 3.2). Beta-blocker treatment had a negative effect on depressive symptoms at both follow-ups 1 (ß = 0.48; 95% CI 09-0.86; P = 0.015) and 2 (ß = 0.41; 95% CI = 0.01-0.81; P = 0.047), but no effect on anxiety. CONCLUSION: Beta-blocker treatment led to a modest increase in depressive symptoms among MI patients with preserved LVEF. This observed effect was most pronounced in individuals with prior beta-blocker treatment. In routine initiation and continuation of beta-blocker treatment, a risk of slightly increased depressive symptoms should be considered.

Effective Treatment of Refractory Cluster Headache With Propranolol.

Cluster headache (CH) is a debilitating neurological condition characterized by excruciating unilateral pain, often accompanied by autonomic symptoms. We present a compelling case report detailing the experience of a 22-year-old male who suffered from refractory CH and exhibited a remarkable response to propranolol. This unique case highlights the potential effectiveness of propranolol in alleviating CH symptoms that are resistant to conventional therapies. Moreover, the absence of reported side effects on such a low dose further underscores its appeal as a treatment option. This case report sheds light on a potential avenue for managing refractory CH, offering hope for individuals who struggle with this debilitating condition.

The sympathetic nervous system shapes the tumor microenvironment to impair chemotherapy response.

The tumor microenvironment influences cancer progression and response to treatments, which ultimately impacts the survival of patients with cancer. The sympathetic nervous system (SNS) is a core component of solid tumors that arise in the body. In addition to influencing cancer progression, a role for the SNS in the effectiveness of cancer treatments is beginning to emerge. This review explores evidence that the SNS impairs chemotherapy efficacy. We review findings of studies that evaluated the impact of neural ablation on chemotherapy outcomes and discuss plausible mechanisms for the impact of neural signaling on chemotherapy efficacy. We then discuss implications for clinical practice, including opportunities to block neural signaling to improve response to chemotherapy.

Efficacy and Safety of Esmolol in Neonatal Cardiac Surgery with Cardiopulmonary Bypass (CPB) for d-Transposition of the Great Arteries (d-TGA).

OBJECTIVE: D-Transposition of the great arteries (d-TGA) is the most common congenital heart disease requiring surgical correction within the neonatal period. Sinus tachycardia often persists postoperatively, potentially affecting cardiac function. This study aimed to investigate the efficacy and safety of the short-acting beta-1-selective beta-blocker esmolol in controlling heart rate in neonatal cardiac surgery with cardiopulmonary bypass (CPB). METHODS: A retrospective cohort study was conducted on neonates undergoing surgery for d-TGA. The study cohort included 112 patients, divided into an esmolol intervention group (n = 57) and a control group (n = 55). Baseline characteristics, hemodynamic parameters and outcome measures were assessed. RESULTS: In the esmolol group, median heart rate at ICU admission was significantly higher compared to the control group (155 vs. 147 bpm, p = 0.018). After a median time of 11 h, heart rate was lower among the esmolol patients (135 vs. 144 bpm, p < 0.001). There were no differences in other hemodynamic parameters between the two groups. Patients treated with esmolol required longer catecholamine support while no difference regarding survival, duration of invasive ventilation and ICU stay were noticed. CONCLUSION: No relevant hemodynamic difference was seen between neonates treated with perioperative esmolol and the control group and outcome did not differ. This indicates non-inferiority of perioperative betablocker therapy in young age. Prospective and placebo-controlled assessment of perioperative esmolol therapy in neonates is needed.

Efficiency of Topical Beta-Blockers for Epistaxis Control in Ulcerated Infantile Hemangioma.

Infantile hemangiomas (IHs) are common childhood benign tumors that are generally self-limiting in nature. However, they can lead to complications, including pain, ulceration, or permanent disfigurement. Successful treatment methods include oral and topical beta-blockers. We report a case of a two-month-old girl, born full-term, who presented with daily epistaxis that began approximately one week after birth. The epistaxis was previously treated with nasal saline drops. Endoscopy revealed an ulcerating hemangioma over the right anterior nasal septum with involvement of the maxillary crest. The remainder of her physical examination was unremarkable, with no concerns for further airway pathologies. We initiated a trial of topical Timolol 0.5% TID for one month while continuing nasal hygiene with saline spray and Vaseline. Epistaxis ceased after only a few days of Timolol use, and substantial improvement in appearance, bleeding, and nasal crusting of the right anterior septum was noted. However, the hemangioma was found to be extending into the anterior soft tissue, including the oral vestibulum. Imaging was obtained, and systemic treatment with propranolol was added to her regimen. The mainstay and first-line treatment for IHs currently consists of topical beta-blockers (such as Timolol) and oral propranolol. In this case, the topical application of Timolol effectively controlled the bleeding and restore function but had limited impact on overall tumor regression, necessitating additional systemic therapy. Although systemic treatment may not always be readily available or may be limited due to potential side effects, early use of topical beta-blockers can be considered a relatively simple and safe first-line treatment option for controlling the symptoms of an intranasal IH in the early life of an infant.

Early initiation of oral beta-blocker improves long-term survival in patients with acute myocardial infarction who underwent primary percutaneous coronary intervention.

BACKGROUND: The optimal timing for the initiation of oral beta-blockers after acute myocardial infarction (MI) remains unclear within the context of current primary percutaneous coronary intervention (PCI) practice. METHODS: This retrospective cohort study included 412 consecutive patients admitted with a diagnosis of acute MI between January 2007 and August 2016 who underwent successful primary PCI and were given oral carvedilol during hospitalization. Early and late carvedilol groups were based on initiation within the first 24 h or after. Propensity score matching (1:1) incorporating 21 baseline characteristics yielded 47 matched pairs. Timing of carvedilol initiation was evaluated in relation to patient outcomes including time to all-cause mortality, using Kaplan-Meier estimates on the matched cohort and additional confirmation in multivariable regression analysis among the entire cohort. RESULTS: Median follow-up period was 828 days. All-cause death occurred in 14 patients (4.7%) and 18 patients (15.8%) of the early and late carvedilol groups. After propensity score matching, initiation of oral carvedilol within the first 24 h was associated with lower all-cause mortality (6.4% vs. 25.5%, hazard ratio 0.28, 95% confidence interval 0.06 - 0.89, p = 0.036), as well as lower in-hospital mortality (0 vs. 14.9%, p = 0.018). CONCLUSIONS: These results provide evidence that initiation of oral carvedilol within the first 24 h reduces the risk of long-term mortality, in acute MI patients who underwent primary PCI, supporting current guidelines recommendation.

Routine beta-blocker therapy after acute coronary syndromes: The end of an era?

BACKGROUND: Beta-blocker therapy, a treatment burdened by side effects including fatigue, erectile dysfunction and depression, was shown to reduce mortality and cardiovascular events after acute coronary syndromes (ACS) in the pre-coronary reperfusion era. Potential mechanisms include protection from ventricular arrhythmias, increased ischaemia threshold and prevention of left ventricular (LV) adverse remodelling. With the advent of early mechanical reperfusion and contemporary pharmacologic secondary prevention, the benefit of beta-blockers after ACS in the absence of LV dysfunction has been challenged. METHODS: The present narrative review discusses the contemporary evidence based on searching the PubMed database and references in identified articles. RESULTS: Recently, the REDUCE-AMI trial-the first adequately powered randomized trial in the reperfusion era to test beta-blocker therapy after myocardial infarction with preserved left ventricular ejection fraction (LVEF)-showed no benefit on the composite of all-cause death or myocardial infarction over a median 3.5-year follow-up. While the benefit of beta-blockers in patients with reduced LVEF remains undisputed, their value in post-ACS patients with mildly reduced systolic function (LVEF 41%-49%) has not been studied in contemporary randomized trials; in this setting, observational studies have suggested a reduction in cardiovascular events with these agents. The adequate duration of beta-blocker therapy remains unknown, but observational data suggests that any mortality benefit may be lost beyond 1-12 months after ACS in patients with LVEF >40%. CONCLUSION: We believe that there is sufficient evidence to abandon routine beta-blocker prescription in post-ACS patients with preserved LV systolic function.

A national analysis of systemic adverse events of beta-blockers used for glaucoma therapy.

PURPOSE: To evaluate systemic complications for timolol, carteolol, levobunolol, and/or betaxalol by using an FDA Federal Adverse Event Reporting System (FAERS). METHODS: We evaluated FAERS for adverse events associated with ß-blocker use for glaucoma. All reported symptoms were reviewed to identify systemic adverse events and to detect safety signals, defined as information on a new or known side effect that may be caused by a medicine. We used the proportional reporting ratio (PRR), reporting odds ratio (ROR), empirical Bayes geometric mean (EBGM), and information component (IC) as a part of a disproportionality analysis comparing the frequency of ß-blocker symptoms with all other adverse event reports. We considered a signal to be detected when all four disproportionality analysis metrics were positive. RESULTS: We found 10,500,309 total adverse event reports from the FAERS database 2004-2022Q3, which included 8,793 case reports with a primary suspect of a ß-blocker use for glaucoma. 1,838 unique adverse symptoms were reported were associated with ß-blocker. Regarding outcomes, there were 165 (1.88%) reports of disability, 671 (7.63%) reports of hospitalisation, and 1,934 (21.99%) reports of some other unspecified complication. Regarding adverse events, the most reported general, cardiac, and respiratory symptoms were respectively dizziness (n = 281), bradycardia (n = 145), and dyspnoea (n = 195). 256 (2.91%) cases of death were reported. We found significant signals on bradycardia (n = 145), complete atrioventricular block (n = 38), and bronchospasm (n = 23). No allergic, endocrine, constitutional, or gastrointestinal symptoms generated positive signals. CONCLUSION: ß-blocker use in glaucoma therapy can be rarely associated with serious systemic and life-threatening complications.

Safety and efficacy of early beta-blocker initiation in acute heart failure and cardiogenic shock: systematic review and meta-analysis.

BACKGROUND: The beta-blocker (BB) initiation in acute heart failure (AHF) patients is still controversial. Some show the benefit of BB employment in decreasing the mortality outcome. This study aims to assess the safety and efficacy of in-hospital and long-term outcomes of BB initiation in AHF hospitalized patients. We searched multiple databases examining the outcome of AHF patients who had administered BB as the therapy initiation. Primary outcomes were all-cause mortality, composite endpoint after BB initiation when hospitalized, and post-discharge all-cause mortality. The secondary outcomes were adverse events after in-hospital BB initiation, including hypotension and symptomatic bradycardia after BB initiation when hospitalization and rehospitalization. RESULTS: Eight cohort studies with 16,639 patients suffering from AHF and cardiogenic shock, with 9923 participants allocated to the early BB group and 6,713 patients in the control group. The follow-up durations ranged from 2 to 24 months. Early BB administration significantly reduced in-hospital composite endpoints (RR: 0.42; 95% CI (0.30-0.58); p < 0.001), in-hospital all-cause mortality (RR: 0.43; 95% CI (0.31-0.61); p < 0.001), discharge mortality (RR: 0.51; 95% CI (0.41-0.63); p < 0.001), and rehospitalization (RR: 0.57; 95% CI (0.44-0.74); p < 0.001). There were no discernible differences in in-hospital BB-related adverse events between the two groups (p = 0.13). Subgroup analyses conducted on AHF patients presenting with cardiogenic shock revealed no significant differences in in-hospital composite endpoint and in-hospital mortality, and similar results were shown in the naive BB population. CONCLUSIONS: The BB initiation in AHF patients shows advantages in efficacy and safety outcome.

Landiolol for heart rate control in patients with septic shock and persistent tachycardia. A multicenter randomized clinical trial (Landi-SEP).

PURPOSE: Excessive tachycardia in resuscitated septic shock patients can impair hemodynamics and worsen patient outcome. We investigated whether heart rate (HR) control can be achieved without increased vasopressor requirements using the titratable highly selective, ultra-short-acting ß1-blocker landiolol. METHODS: This randomized, open-label, controlled trial was conducted at 20 sites in 7 European countries from 2018 to 2022 and investigated the efficacy and safety of landiolol in adult patients with septic shock and persistent tachycardia. Patients were randomly assigned to receive either landiolol along with standard treatment (n = 99) or standard treatment alone (n = 101). The combined primary endpoint was HR response (i.e., HR within the range of 80-94 beats per minute) and its maintenance without increasing vasopressor requirements during the first 24 h after treatment start. Key secondary endpoints were 28-day mortality and adverse events. RESULTS: Out of 196 included septic shock patients, 98 received standard treatment combined with landiolol and 98 standard treatment alone. A significantly larger proportion of patients met the combined primary endpoint in the landiolol group than in the control group (39.8% [39/98] vs. 23.5% [23/98]), with a between-group difference of 16.5% (95% confidence interval [CI]: 3.4-28.8%; p = 0.013). There were no statistically significant differences between study groups in tested secondary outcomes and adverse events. CONCLUSION: The ultra-short-acting beta-blocker landiolol was effective in reducing and maintaining HR without increasing vasopressor requirements after 24 h in patients with septic shock and persistent tachycardia. There were no differences in adverse events and clinical outcomes such as 28-day mortality vs. standard of care. The results of this study, in the context of previous trials, do not support a treatment strategy of stringent HR reduction (< 95 bpm) in an unselected septic shock population with persistent tachycardia. Further investigations are needed to identify septic shock patient phenotypes that benefit clinically from HR control.

Calcium channel blockers and beta blockers in pediatric supraventricular tachycardia.

INTRODUCTION: Supraventricular tachycardia (SVT) is a common pediatric arrhythmia. Beta blockers (BBs) and calcium channel blockers (CCBs) are used for treatment despite little data examining their use. We describe the prescriptive tendencies, efficacy, and tolerability of BBs and CCBs used in the treatment of pediatric SVT. METHODS AND RESULTS: This is a multicenter retrospective cohort study from three academic children's hospitals. Individuals aged 1-21 years at time of SVT diagnosis initiated on a BB or a CCB between 01/01/2010 and 12/31/2020 were included. Exclusion criteria were pre-excitation, ectopic atrial tachycardia, and hemodynamically significant heart disease. Demographic, comorbidity, symptomatology, and medication data were collected. Treatment success was defined using a composite data abstraction tool. Of 164 patients, 151 received a BB and 13 received a CCB. The success rate on the initial dosage was 46% for both BB and CCB; the success rate following dosage adjustments was also comparable for BBs (98/151, 65%) and CCBs (9/13, 69%). While 27 (18%) BB patients experienced intolerable side effects, no CCB patient did. CONCLUSION: Treatment with a BB or CCB was successful in half of patients. BBs were prescribed more frequently than CCBs but were associated with more side effects.

Does atenolol use during pregnancy cause small for gestational age neonates? A meta-analysis.

OBJECTIVES: Atenolol is a commonly used beta bloscker in non-pregnant women. Many providers are hesitant in prescribing atenolol in pregnancy because of a possible association with poor fetal growth. We aimed to assess the association between atenolol and the occurrence of small for gestational age neonates compared to other beta blockers, as described in the existing literature. METHODS: We used the meta-analytic method to generate a forest plot for risk ratios (RR) of small for gestational age in patients who used atenolol vs. other beta blockers. Statistical heterogeneity was assessed with the I2 statistic. RESULTS: Two studies were included, with a resultant RR of 1.94 [95 % confidence interval (CI) 1.60; 2.35]. A study by Duan et al. in 2018 noted the following rate of small for gestational age for each beta blocker use: 112/638 atenolol, 590/3,357 labetalol, 35/324 metoprolol, and 50/489 propranolol. A study by Tanaka et al. in 2016 noted the following rate of small for gestational age: 8/22 for propranolol, 2/12 for metoprolol, 2/6 for atenolol, 0/5 for bisoprolol. Heterogeneity (I2) was 0 %. CONCLUSIONS: Our results suggested an elevated risk of small for gestational age associated with atenolol use in comparison to other beta blockers, specifically labetalol, propranolol, bisoprolol, and metoprolol.

Propranolol to decrease time to delivery: a meta-analysis of randomized controlled trials.

OBJECTIVE: To assess the effect of propranolol on time to delivery among patients undergoing induction or augmentation of labor. DATA SOURCES: PubMed, Scopus, Cochrane Library, ClinicalTrials.gov, and CINAHL (EBSCO) were searched from inception to December 2023. STUDY ELIGIBILITY CRITERIA: Randomized controlled trials (RCTs) that examined the impact of propranolol on time to delivery among patients undergoing induction or augmentation of labor were included. RCTs that included stillbirth before randomization, non-randomized trials, observational, cohort, case control, or studies in which the control group included an intervention other than standard care were excluded. STUDY APPRAISAL AND SYNTHESIS METHODS: Primary outcome was time to delivery after administration of propranolol among patients undergoing induction or augmentation of labor. The summary measures were reported as summary mean difference (MD) or relative risk with 95% confidence interval (CI). RESULTS: Nine RCTs including 1,182 patients were included in this meta-analysis. Five studies investigated the effect of propranolol among patients undergoing induction of labor (IOL) and demonstrated a significant decrease in time to delivery (MD, -91.5 minutes, 95% CI -110.6 to -72.4). Four studies investigated the effect of propranolol among patients undergoing augmentation of labor and showed no significant decrease in time to delivery (MD, -2.98 minutes, 95% CI -21.6 to 15.6). Our pooled analysis demonstrated that the use of propranolol in IOL and augmentation was associated with a decrease in time to delivery from administration of propranolol compared to placebo (mean difference, -46.15 minutes, 95% CI -59.48 to -32.81). The meta-analysis found no increased risk of PPH, blood transfusion, cesarean delivery rates, or NICU admission with the use of propranolol during labor. CONCLUSION: The use of propranolol during induction of labor shortens overall time to delivery by about 91 minutes and did not significantly decrease time to delivery in those undergoing augmentation of labor.

Beta-blocker use and outcomes in patients with heart failure and mildly reduced and preserved ejection fraction.

AIMS: In the absence of randomized trial evidence, we performed a large observational analysis of the association between beta-blocker (BB) use and clinical outcomes in patients with heart failure (HF) and mildly reduced (HFmrEF) and preserved ejection fraction (HFpEF). METHODS AND RESULTS: We pooled individual patient data from four large HFmrEF/HFpEF trials (I-Preserve, TOPCAT, PARAGON-HF, and DELIVER). The primary outcome was the composite of cardiovascular death or HF hospitalization. Among the 16 951 patients included, the mean left ventricular ejection fraction (LVEF) was 56.8%, and 13 400 (79.1%) had HFpEF (LVEF ≥50%). Overall, 12 812 patients (75.6%) received a BB. The median bisoprolol-equivalent dose of BB was 5.0 (Q1-Q3: 2.5-5.0) mg with BB continuation rates of 93.1% at 2 years (in survivors). The unadjusted hazard ratio (HR) for the primary outcome did not differ between BB users and non-users (HR 0.98, 95% confidence interval [CI] 0.91-1.05), but the adjusted HR was lower in BB users than non-users (0.81, 95% CI 0.74-0.88), and this association was maintained across LVEF (pinteraction = 0.88). In subgroup analyses, the adjusted risk of the primary outcome was similar in BB users and non-users with or without a history of myocardial infarction, hypertension, or a baseline heart rate <70 bpm. By contrast, a better outcome with BB use was seen in patients with atrial fibrillation compared to those without atrial fibrillation (pintreraction = 0.02). CONCLUSIONS: In this observational analysis of non-randomized BB treatment, there was no suggestion that BB use was associated with worse HF outcomes in HFmrEF/HFpEF, even after extensive adjustment for other prognostic variables.

Effects of Selective and Nonselective Beta Blockers on Bone Mineral Density in Mexican Patients with Breast Cancer.

Breast cancer (BCa) is related to chronic stress and can reduce the bone mineral density (BMD) through neurochemicals related to beta-adrenergic receptor (ADRB) 1 and 2. Selective beta blockers (sBBs) and nonselective beta blockers (nsBBs) are used to treat systemic arterial hypertension (SAH) and may have osteoprotective effects, as they inhibit ADRBs. To evaluate the effects of sBBs and nsBBs on the BMD of Mexican patients with BCa. A retrospective study was conducted. We included 191 Mexican women with BCa without SAH and with SAH treated with nsBBs, sBBs, and diuretics. BMD was evaluated using a bone density scan (DEX scan). A greater average BMD (p < 0.05) was observed in patients with prior treatment with both nsBBs and sBBs (0.54 ± 0.94 and -0.44 ± 1.22, respectively) compared to patients treated with diuretics or without SAH (-1.73 ± 0.83 and -1.22 ± 0.98, respectively). Regarding the diagnosis of osteoporosis/osteopenia, no cases were observed in patients treated with nsBBs, whereas 5.6% of the patients treated with sBBs presented osteopenia. A total of 23.1% and 10.6% patients managed with diuretics or without treatment presented with osteoporosis and 61.5% and 48% patients managed with loop diuretics and without treatment presented with osteopenia, respectively (p < 0.05). Treatment with nsBBs is a promising option for the prevention and management of osteoporosis/osteopenia in Mexican patients with BCa; however, further prospective studies are needed.

Systemic and cerebro-cardiac biomarkers following traumatic brain injury: an interim analysis of randomized controlled clinical trial of early administration of beta blockers.

This is an interim analysis of the Beta-blocker (Propranolol) use in traumatic brain injury (TBI) based on the high-sensitive troponin status (BBTBBT) study. The BBTBBT is an ongoing double-blind placebo-controlled randomized clinical trial with a target sample size of 771 patients with TBI. We sought, after attaining 50% of the sample size, to explore the impact of early administration of beta-blockers (BBs) on the adrenergic surge, pro-inflammatory cytokines, and the TBI biomarkers linked to the status of high-sensitivity troponin T (HsTnT). Patients were stratified based on the severity of TBI using the Glasgow coma scale (GCS) and HsTnT status (positive vs negative) before randomization. Patients with positive HsTnT (non-randomized) received propranolol (Group-1; n = 110), and those with negative test were randomized to receive propranolol (Group-2; n = 129) or placebo (Group-3; n = 111). Propranolol was administered within 24 h of injury for 6 days, guided by the heart rate (> 60 bpm), systolic blood pressure (≥ 100 mmHg), or mean arterial pressure (> 70 mmHg). Luminex and ELISA-based immunoassays were used to quantify the serum levels of pro-inflammatory cytokines (Interleukin (IL)-1ß, IL-6, IL-8, and IL-18), TBI biomarkers [S100B, Neuron-Specific Enolase (NSE), and epinephrine]. Three hundred and fifty patients with comparable age (mean 34.8 ± 9.9 years) and gender were enrolled in the interim analysis. Group 1 had significantly higher baseline levels of IL-6, IL-1B, S100B, lactate, and base deficit than the randomized groups (p = 0.001). Group 1 showed a significant temporal reduction in serum IL-6, IL-1ß, epinephrine, and NSE levels from baseline to 48 h post-injury (p = 0.001). Patients with severe head injuries had higher baseline levels of IL-6, IL-1B, S100B, and HsTnT than mild and moderate TBI (p = 0.01). HsTnT levels significantly correlated with the Injury Severity Score (ISS) (r = 0.275, p = 0.001), GCS (r = - 0.125, p = 0.02), and serum S100B (r = 0.205, p = 0.001). Early Propranolol administration showed a significant reduction in cytokine levels and TBI biomarkers from baseline to 48 h post-injury, particularly among patients with positive HsTnT, indicating the potential role in modulating inflammation post-TBI.Trial registration: ClinicalTrials.gov NCT04508244. It was registered first on 11/08/2020. Recruitment started on 29 December 2020 and is ongoing. The study was partly presented at the 23rd European Congress of Trauma and Emergency Surgery (ECTES), April 28-30, 2024, in Estoril, Lisbon, Portugal.