The Role of Aldosterone Blockade in Post-MI Heart Failure

Abstract

Aldosterone is an important mediator of the renin-angiotensin-aldosterone system (RAAS) and plays a major role in the pathophysiology of cardiovascular disease as well as regulation of fluid and electrolyte balance. In experimental models, aldosterone has been shown to promote endothelial dysfunction, induce vascular inflammation, myocardial ischemia and necrosis, increase collagen synthesis in cardiac fibroblasts, contribute to plasminogen activator inhibitor-1 regulation, decrease baroreceptor sensitivity and reflex function, block myocardial uptake of norepinephrine, increase oxidative stress, and stimulate cardiomyocyte apoptosis. Experimental data as well as clinical research has shown that aldosterone stimulates myocardial fibrosis and promotes LV remodeling post-MI. Moreover, therapy with ACE inhibitors or angiotension receptor blockers cannot adequately suppress these harmful effects of aldosterone. The Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS) demonstrated that selective aldosterone blockade with eplerenone significantly reduced mortality and morbidity when used in addition to standard therapy, including ACE inhibitors or ARBs and β-blockers, in patients with AMI complicated by LVSD and heart failure. The benefits of eplerenone on all-cause mortality and sudden cardiac death in EPHESUS were observed within 30 days of randomization, indicating the benefit of early initiation of treatment with eplerenone post-infarction, in addition to standard therapy. Recent ACC/ AHA and the HFSA guidelines have recommended the use of eplerenone in post-MI HF patients. Incorporation of eplerenone use into hospital critical pathways, and dissemination of information regarding patient selection, drug administration and monitoring of serum potassium are important steps to encourage increased utilization of this therapy in clinical practice.