Genetic Variants in the Renin Angiotensin Aldosterone System and their Impact on Mineralocorticoid Receptor Antagonist Response After Myocardial Infarction: A Comprehensive Review

Despite improvements in pharmacological treatments, myocardial infarction (MI) continues to be a major cause of heart failure and a global health burden. By inhibiting aldosterone-mediated pathways implicated in inflammation, oxidative stress, and cardiac fibrosis, mineralocorticoid receptor antagonists (MRAs), such as spironolactone and eplerenone, have demonstrated efficacy in the treatment of MI. The wide range of clinical responses to MRAs, however, emphasizes the necessity of precision medicine strategies. By modifying receptor sensitivity, aldosterone synthesis, and downstream signaling, genetic variations within the renin-angiotensin-aldosterone system (RAAS), specifically in genes like CYP11B2, NR3C2, ACE, AGT, and AGTR1, may have a substantial impact on MRA efficacy. With an emphasis on functional outcomes measured by echocardiographic parameters and a variety of circulating biomarkers, such as aldosterone, total antioxidant capacity (TAC), transforming growth factor-beta1 (TGF-β1), interleukin-6 (IL-6), and brain natriuretic peptide (BNP), this review examines the available data on RAAS-related genetic variations and their relationship to MRA response in MI patients. We also go over how pharmacogenomic testing may help direct customized treatment, minimize side effects, and improve long-term cardiovascular results. More focused, efficient management techniques in post-MI care may be possible with an understanding of the gene-drug interactions within the RAAS pathway.