Effect of aldosterone blockade in patients with systolic left ventricular dysfunction: implications of the RALES and EPHESUS studies.
Aldosterone blockade has been shown to be effective in reducing total mortality as well as hospitalization for heart failure in patients with systolic left ventricular dysfunction (SLVD) due to chronic heart failure and in patients with SLVD post acute myocardial infarction. The evidence for the effectiveness of aldosterone blockade in chronic heart failure comes from the randomized aldactone evaluation study (RALES) while that for patients post infarction from the eplerenone post acute myocardial infarction efficacy and survival study (EPHESUS). These studies suggest that mineralocorticoid receptor activation remains important despite the use of an angiotensin converting enzyme-inhibitor/angiotensin receptor blocking (ARB) agent and a beta blocker. Increasing evidence suggest that aldosterone blockade has important effects not only on the kidney but on ventricular remodeling, myocardial fibrosis, autonomic balance, fibrinolysis, oxidative stress, and activation of the NF-kappaB and AP-1 signaling pathways. The results of these studies in patients with SLVD has important implications not only for patients with chronic heart failure and post infarction but also for the therapy of patients with essential hypertension and other cardiovascular diseases.
Pitt
Bertram
B
University of Michigan School of Medicine, Ann Arbor, MI, USA. bpitt@umich.edu
D000450:Aldosterone / Q000378:metabolism; D057911:Angiotensin Receptor Antagonists; D004077:Digoxin / Q000008:administration & dosage*; D004791:Enzyme Inhibitors / Q000008:administration & dosage*; D000077545:Eplerenone; D005260:Female; D006801:Humans; D008297:Male; D000451:Mineralocorticoid Receptor Antagonists / Q000008:administration & dosage*; D009203:Myocardial Infarction / Q000150:complications / Q000378:metabolism; D016032:Randomized Controlled Trials as Topic; D013148:Spironolactone / Q000008:administration & dosage* / Q000031:analogs & derivatives*; D013599:Systole / Q000502:physiology; D018487:Ventricular Dysfunction, Left / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000401:mortality
D057911:Angiotensin Receptor Antagonists; D004791:Enzyme Inhibitors; D000451:Mineralocorticoid Receptor Antagonists; D013148:Spironolactone; D000450:Aldosterone; D000077545:Eplerenone; D004077:Digoxin