Pharmacotherapy of Heart Failure: A Narrative Review of Contemporary Guideline-Directed Drug Therapy

Heart failure remains one of the most common, costly, and lethal cardiovascular msyndromes worldwide, affecting more than 64 million people globally and carrying a prognosis that is often worse than many forms of cancer. Over the past four decades, pharmacological management has evolved from a purely symptomatic, diuretic centred approach into a sophisticated, evidence-driven strategy that targets the neurohormonal maladaptation underlying the disease. This narrative review summarizes the pharmacotherapy of heart failure with a focus on guideline-directed medical therapy (GDMT) for heart failure with reduced ejection fraction (HFrEF). We discuss the mechanistic rationale, clinical evidence, dosing principles, and safety considerations of the four foundational drug classes — renin–angiotensin system inhibitors (including angiotensin receptor–neprilysin inhibitors), evidence-based beta blockers, mineralocorticoid receptor antagonists, and sodium–glucose cotransporter-2 inhibitors — followed by symptom-directed agents such as loop diuretics, digoxin, ivabradine, and vericiguat. Special attention is given to heart failure with preserved ejection fraction, comorbidity-driven choices, and the practical challenge of up titration and adherence. Collectively, modern combination therapy has transformed heart failure from an inexorably fatal condition into a chronic disease in which survival and quality of life can be meaningfully improved.