Nebivolol in the therapeutic landscape of heart failure: Mechanisms and clinical outcomes

Heart failure (HF) remains a major global health challenge, marked by clinical heterogeneity and high morbidity, especially among elderly and comorbid patients. While β-blockers are central to HF management, conventional agents often present tolerability limitations, particularly in populations with preserved ejection fraction (HFpEF) or impaired vascular function. Nebivolol, a third-generation β-blocker characterized by high β₁-selectivity and nitric oxide-mediated vasodilation, offers a differentiated therapeutic profile with potential advantages in these subgroups. This review synthesizes current evidence on nebivolol's pharmacologic mechanisms, including its dual action on adrenergic and endothelial pathways, as well as its antioxidant and anti-inflammatory effects. Preclinical studies and translational biomarkers support their vascular and myocardial protective actions, while the SENIORS trial provides pivotal clinical evidence demonstrating efficacy across ejection fraction spectrums in elderly HF patients. Comparative data further reinforces its tolerability and favorable metabolic impact relative to traditional β-blockers. Nebivolol's role is also explored in guideline contexts and its potential utility in special populations such as those with renal impairment, diabetes, or cancer therapy-related cardiac dysfunction. Looking ahead, advances in pharmacogenomics, digital phenotyping, and adaptive trial designs may help personalize nebivolol therapy. This review underscores nebivolol's emerging position in the evolving landscape of HF treatment.