Advances in the pharmacological management of heart failure with reduced ejection fraction: A narrative review

Background: Heart failure with reduced ejection fraction (HFrEF) is a chronic and progressive cardiovascular syndrome associated with high morbidity, mortality, and healthcare utilisation worldwide. Despite significant advances in cardiovascular medicine, patients with HFrEF continue to experience frequent hospitalisations and impaired quality of life. Over the past decade, an improved understanding of the complex pathophysiology of HFrEF, including neurohormonal activation, maladaptive ventricular remodelling, inflammation, and metabolic dysfunction, has driven the development of multiple disease-modifying pharmacotherapies and updated treatment paradigms. Methods: This narrative review synthesises contemporary evidence published between 2020 and 2025 on the pathophysiology and pharmacological management of HFrEF. Major randomised controlled trials, meta-analyses, and international guideline documents were reviewed to evaluate established and emerging therapies, including angiotensin receptor–neprilysin inhibitors, beta-blockers, mineralocorticoid receptor antagonists, sodium–glucose cotransporter-2 inhibitors, and newer agents such as ivabradine, vericiguat, and omecamtiv mecarbil. Particular emphasis was placed on mechanisms of action, clinical outcomes, and the expanding role of clinical pharmacists and Pharm D professionals in optimising guideline-directed medical therapy. Conclusion: The management of HFrEF has evolved toward early, multidrug, guideline-directed therapy targeting multiple pathophysiological pathways. Integrating emerging pharmacological agents with pharmacist-led care models offers substantial potential to improve adherence, reduce hospital readmissions, and enhance long-term clinical outcomes in patients with HFrEF.