Role of Neurohormonal Modulators in Reducing Adverse Outcomes in Patients with Ischemic Heart Disease.

Abstract

Neurohormonal modulators mitigate adverse outcomes in ischemic heart disease (IHD) by targeting maladaptive activation of the renin-angiotensin-aldosterone system (RAAS) and sympathetic nervous system (SNS), both of which contribute to disease progression. This narrative review summarizes and critically evaluates conventional and emerging neurohormonal modulators in IHD management. Angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs), beta-blockers, mineralocorticoid receptor antagonists (MRAs), and angiotensin receptor-neprilysin inhibitors (ARNIs) counteract vasoconstriction, inflammation, fibrosis, and adverse ventricular remodelling. ACE inhibitors and ARBs reduce RAAS-mediated injury, while beta-blockers limit myocardial oxygen demand and arrhythmia risk by attenuating SNS overactivation. MRAs block aldosterone-mediated sodium retention and myocardial fibrosis, whereas ARNIs enhance natriuretic peptide signaling to mitigate fluid overload and structural remodeling. In addition, sodium- glucose cotransporter-2 (SGLT2) inhibitors improve metabolic efficiency and hemodynamic stability, extending the benefits of neurohormonal modulation beyond traditional pathways. Collectively, these agents improve cardiac function, reduce hospitalizations, and enhance survival, as demonstrated in clinical trials. This review highlights their complementary mechanisms, current limitations, and future therapeutic directions, underscoring their central role in contemporary IHD management and in improving quality of life.