Beta-blockers are among the most widely prescribed drugs in the management of both supraventricular and ventricular arrhythmias, and they are frequently regarded as a homogeneous pharmacological class. They are not. The agents in current use differ substantially in beta1-receptor selectivity, lipophilicity, half-life, route of administration, intrinsic sympathomimetic activity, and ancillary properties, and arrhythmias themselves differ in mechanism, adrenergic dependence, anatomical origin, and structural substrate. This narrative review examines whether these pharmacological differences translate into clinically meaningful differences in efficacy and utility, asking not only whether a beta-blocker should be used but which one should be used. Evidence was drawn from a targeted search of PubMed, Web of Science, Scopus, Ovid, Embase, and the Cochrane Library, with priority given to randomized controlled trials, meta-analyses, large registries, and contemporary society guidelines, and was synthesized qualitatively by arrhythmia type. A class effect is apparent for many indications, particularly rate control in atrial fibrillation and atrial flutter, where metoprolol, bisoprolol, and carvedilol perform broadly similarly and the choice is driven mainly by comorbidity and tolerability. Drug-specific differences emerge in three settings. In adrenergically mediated inherited syndromes, namely catecholaminergic polymorphic ventricular tachycardia and long QT syndrome, nonselective agents and especially nadolol are clearly superior to beta1-selective agents, and the same principle appears to extend to ventricular electrical storm, in which propranolol has outperformed metoprolol in a randomized comparison. In acute care, pharmacokinetics dominate, and the ultra-short-acting agents esmolol and landiolol permit a degree of titration that longer-acting drugs cannot match. In patients with heart failure and reduced ejection fraction, carvedilol, metoprolol succinate, and bisoprolol should be preferred irrespective of arrhythmia subtype because of their established mortality benefit. Conversely, beta1-selective agents, including the highly selective agent nebivolol, improve tolerability in bronchospastic disease, although this reflects respiratory tolerability rather than any demonstrated antiarrhythmic advantage, and beta-blockers have little role in Brugada syndrome or in bradycardia-dependent acquired torsades de pointes. Beta-blockers should therefore not be treated as interchangeable. Selection should integrate arrhythmic mechanism, structural substrate, and patient characteristics, and head-to-head trials remain conspicuously scarce.

Background: Beta-blockers (BBs) remain a foundation of cardiovascular therapy. However, cumulative evidence suggests that metabolic adverse effects may differ significantly between individual sub-classes. While conventional BBs have been associated with changes in glucose and lipid metabolism, the comparative real-world reporting patterns of these events have not been comprehensively evaluated. Objective: We investigated the association between selected BBs and metabolic diseases using a large pharmacovigilance database and compared the reporting profiles of metoprolol (MET), carvedilol (CAR), bisoprolol (BIS), and nebivolol (NEB). Methods: A descriptive and disproportionality analysis was performed using Individual Case Safety Reports (ICSRs) submitted to the EudraVigilance database up to 26 April 2026. Metabolic adverse events were grouped into pathophysiological categories, including dysglycemia and type 2 diabetes mellitus (T2DM), lipid disorders, obesity-related disorders, inflammatory biomarkers, and hepatic steatosis. Reporting odds ratios (RORs) with 95% confidence intervals (CI) were calculated to identify disproportional reporting signals. To improve clinical reliability, a stratified analysis restricted to healthcare professional (HP)-submitted reports was conducted. Results: A total of 63.744 ICSRs were identified for the four BBs, including 27.169 for MET, 21.860 for BIS, 9487 for CAR, and 5228 for NEB. Dysglycemic events represented the most frequently reported metabolic category, with hyperglycemia and T2DM accounting for 155 reports each. MET was associated with the highest number of reports for T2DM, obesity, hepatic steatosis, and elevated triglycerides. In HP-submitted reports, MET showed significantly higher reporting odds of increased triglycerides, obesity, inflammation, and T2DM than BIS and/or CAR. CAR showed higher reporting odds for hyperglycemia and obesity compared with BIS, whereas BIS and, particularly, NEB presented comparatively lower reporting frequencies for metabolic diseases. No significant differences were observed for hepatic steatosis, decreased high density lipoprotein cholesterol (HDL-C), or impaired glucose tolerance. Conclusions: This large-scale pharmacovigilance study highlights substantial heterogeneity in the reporting of metabolic adverse events among commonly prescribed BBs. MET and to a lesser extent CAR were associated with higher reporting odds of metabolic diseases, whereas BIS and especially NEB demonstrated more favorable reporting profiles. Although causality cannot be established from spontaneous reporting data, these findings support individualized BB selection and closer metabolic monitoring in patients with cardiometabolic risk factors.

G protein-coupled receptors (GPCRs) can trigger distinct signaling pathways depending on their localization. Because their appearance is not restricted, GPCRs can signal not only from the plasma membrane but also from internalized compartments. The pH of endosomes is significantly lower compared to the extracellular environment, and thus, location-biased ligands can be developed by carefully adjusting their physicochemical properties. This work describes the development of pH-sensitive β-adrenergic receptor antagonists with weak basicity, conferring enrichment in acidic compartments. Starting from FDA-approved β-blockers including bisoprolol, metoprolol, propranolol, and nebivolol, chemical synthesis, physicochemical studies, in vitro pharmacological investigations, and structure-activity relationship studies led to ligands with considerably higher potency at representative acidic pH values of 6 and 6.5 compared to a pH of 7.4, which is typical for ligand binding at the plasma membrane. Bis-fluorination in the beta position of nitrogen substituents was the most effective and led to pH-sensitive analogs of bisoprolol, metoprolol, and propranolol with 10- to 12-fold higher potencies at endosome-specific pH values. Because endosomal β-adrenergic receptors are suggested to be associated with heart hypertrophy and cardiac dysfunction, the newly developed ligands may serve as lead compounds for the development of powerful and safe cardioprotective drugs.

Prior research has conducted a limited number of studies on the efficacy of atenolol in preventing atrial fibrillation following cardiac surgery (CS). Consequently, a comprehensive evaluation and meta-analysis were undertaken to assess the effectiveness and safety of atenolol in patients undergoing CS for the prevention of postoperative atrial fibrillation (POAF). A meta-analysis of randomized controlled trials was performed. Searches were conducted across multiple databases up to December 1, 2024. The primary focus was the incidence of POAF. Risk ratios (RRs) for treatment effects on dichotomous variables were calculated. The data analysis encompassed 6 randomized controlled trials involving a total of 870 patients. The meta-analysis revealed that atenolol significantly reduces the incidence of POAF in adult patients undergoing CS (RR, 0.55; 95% confidence interval [CI]: 0.32-0.93; P = .03) with moderate heterogeneity (I2 = 57%; P = .10). Atenolol did not demonstrate superiority over sotalol in reducing POAF (RR, 2.39; 95% CI: 1.41-4.04; P = .001) with moderate heterogeneity (I2 = 40%; P = .19). Furthermore, no significant difference was observed between atenolol and the control group (comprising propafenone, metoprolol, nebivolol, and digoxin) in the prevention of POAF (RR, 1.28; 95% CI: 0.76-2.16; P = .35) with moderate heterogeneity (I2 = 43%; P = .15). Recent studies suggest that atenolol could be a safe and effective intervention for the prevention of POAF in adult patients undergoing CS.

Aging is characterized by interconnected disturbances in oxidative stress, chronic inflammation, mitochondrial dysfunction, and nutrient-sensing pathways that collectively contribute to progressive metabolic and vascular decline. Among the central molecular mechanisms implicated in these processes are dysregulation of the AMPK-mTOR-SIRT1 axis, persistent NF-κB activation, impaired Nrf2-mediated antioxidant defense, and mitochondrial redox imbalance. Pharmacological strategies capable of modulating multiple components of this network have therefore gained increasing interest in aging-related research. Empagliflozin, a sodium-glucose cotransporter-2 (SGLT2) inhibitor, has demonstrated pleiotropic metabolic effects extending beyond glycemic control, including modulation of AMPK signaling, attenuation of oxidative stress, and suppression of inflammatory activation. Nebivolol, a third-generation β1-selective adrenergic blocker with nitric oxide-mediated vasodilatory properties, has been associated with endothelial protection, vascular redox regulation, and anti-inflammatory activity. Although both agents influence pathways relevant to aging biology, current evidence is derived predominantly from experimental models of cardiovascular or metabolic disease rather than from physiological aging studies. Moreover, direct evidence evaluating their combined effects in aging remains unavailable. This review critically examines the mechanistic roles of empagliflozin and nebivolol within the context of aging-associated metabolic and vascular dysfunction. Particular emphasis is placed on their reported interactions with AMPK-mTOR-SIRT1 signaling, Nrf2-dependent antioxidant responses, NF-κB-mediated inflammation, mitochondrial function, and endothelial homeostasis. In addition, the review discusses current limitations in the evidence base, including the predominance of reductionist experimental approaches, limited translational validation, and the absence of direct combinational investigations. Comparative consideration is also given to established aging-relevant candidates, including metformin, rapamycin, resveratrol, GLP-1 receptor agonists, NAD[+] modulators, and senolytic strategies, in order to contextualize the potential relevance and limitations of metabolic-vascular pathway modulation in aging research. Rather than proposing definitive evidence of aging-relevant efficacy, the available literature supports a biologically plausible framework in which modulation of metabolic and vascular pathways may influence interconnected mechanisms underlying aging-related decline. Further integrative experimental and translational studies are required to determine whether coordinated targeting of these pathways may provide meaningful therapeutic benefit in aging and age-associated disorders.

Cardiovascular diseases, such as hypertension, coronary artery diseases (CAD), arrhythmias, and chronic heart failure (CHF), often require treatment with beta-blockers. These conditions frequently coexist with chronic obstructive pulmonary disease (COPD), which can complicate therapeutic decisions. Indeed, patients with moderate-to-severe COPD are frequently not given these agents out of concern for possible bronchoconstriction arising from blockade of β2-adrenoceptors in the airways. Observational studies, and meta-analyses support the cardiovascular benefits of β-blockade in people with COPD and cardiovascular diseases. Recent trials evaluating cardioselective β-blockade suggest that cardioselective beta-blockers such as bisoprolol, metoprolol and nebivolol are safe and likely beneficial in those patients that would benefit from their intake due to presence of cardiac comorbid diseases. The aim of this systematic review is to summarise the recent trials and indications for use of cardioselective β-blockers in patients with COPD.

Cyclophosphamide is a chemotherapy drug used to treat various types of neoplasms and autoimmune diseases. During its hepatic metabolism, acrolein is formed, a toxic metabolite responsible for increasing oxidative stress in tissues such as the kidney. Acrolein-induced oxidative stress is characterized by the excessive formation of reactive oxygen species (ROS) and lipid peroxidation. Additionally, the release of pro-inflammatory cytokines leads to the accumulation of immune cells in the renal cortex. Therefore, cyclophosphamide-induced nephrotoxicity is a limiting factor in cancer treatment, creating a need to find nephroprotective agents that reduce renal oxidation and inflammation. Nebivolol is a third-generation β-blocker with established antioxidant effects. This study aimed to evaluate the cytoprotective properties of nebivolol in the renal cortex of mice exposed to cyclophosphamide. Male C57Bl/6 mice were intraperitoneally injected with a single dose of cyclophosphamide (300 mg/kg). Nebivolol (10 mg/kg/day) was administered by gavage for 5 days prior to cyclophosphamide injection. Nebivolol prevented the cyclophosphamide-induced increase in serum creatinine levels. The cyclophosphamide-induced increases in lipoperoxidation and NADPH oxidase-derived superoxide (O2 [•] [-]) were mitigated by nebivolol. The anti-inflammatory effects of nebivolol included a reduction in the number of neutrophils and macrophages in the renal tissue of cyclophosphamide-treated animals. Finally, nebivolol prevented the cyclophosphamide-induced increase in metalloproteinase (MMP)-2 and MMP-9 activities. In summary, cyclophosphamide induces renal dysfunction through pro-oxidative and pro-inflammatory mechanisms. Nebivolol exerts nephroprotective effects via antioxidant and anti-inflammatory pathways, preventing cyclophosphamide-induced renal dysfunction. These beneficial effects suggest nebivolol could help prevent the renal toxicity associated with cyclophosphamide.