Abstract
The mechanisms associated with aldosterone production both systemically and locally as well as the effects of aldosterone blockade on the pathophysiology of heart failure (HF) have been extensively reviewed in this series and elsewhere. This article will review the clinical evidence supporting the use of aldosterone blocking agents (AB)in patients with HF and speculate on some potential future uses.
Similar content being viewed by others
References
Pitt, B, Zannad F, Remme WJ, Cody R, Castaigne A, Perez A, et al. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. N Engl J Med 1999;341:709–717.
Pitt, B, Remme W, Zannad F, Neaton J, Martinez F, Roniker B, Bittman R, Hurley S, Kleiman J, Gatlin M, of the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival study Investigators. Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. N Eng J Med 2003;348(14):1309–1321.
Hohnloser SH, Heinz Kuck K, Dorian P, Roberts RS, Tech M, Hampton JR, Hatala R, Fain E, Gent M. Connolly. Prophylacticuse of an implantable cardioverter-defibrillator after acute myocardial infarction. SJ NEJM 2004;351:2481–2488.
Moss AJ, Zareba W, Hall WJ, Klein H, Wlber DJ, Cannom DS, et al. Prophylactic implantation of a defibrillator in patients with myocardial infarction and reduced ejection fraction. N Engl J Med 2002;346:877–883.
Hayashi M, Tsutamoto T, Wada A, et al. Immediate administration of mineralocorticoid receptor antagonist spironolactone prevents post-infarct left ventricular remodeling associated with suppression of a marker of myocardial collagen synthesis in patients with first anterior acute myocardial infarction. Circulation 2003;107:2259–2265.
de Gasparo M, Joss U, Ramjoue HP. Three new epoxy-spironolactone derivatives: Characterization in vivo and in vitro. J. Pharmacol Exp Ther 1987;240:650–656.
Ravis WR, Reid S, Roniker B, et al. Pharmacokinetics of eplerenone after single and multiple dosing in subjects with and without renal impairment. Clin Pharmacol There 2004;75:P37.
Pfeiffer MA, McMurray JJ, Valazques EJ, Rouleau JL, Kober L, Maggioni AP, et al. Valsartan, captopril, or both in myocardial infarction complicated by heart failure, left ventricular dysfunction, or both. N Eng J Med 2003;349:1893–1906.
Cohn JN, Tognoni G. A randomized trial of the angiotensin-receptor blocker valsartan in chronic heart failure. N Engl J Med 2001:345:1667–1675.
Pfeffer MA, McMurray JJ, Velazquez EJ, Rouleau JL, Kober L, Maggioni AP, Solomon SD, Swedberg K, Van de Werf F, White H, Leimberger JD, Henis Marc, Edwards S, Zelenkofske S, Sellers MA, Califf RM. For the Valsartan in Acute Myocardial Infarction Trial Investigators. Valsartan, captopril, or both in myocardial infarction complicated by heart failure, left ventricular dysfunction or both. N Eng J Med 2003;349:1893–1906.
Tsutamoto T, Wada A, Maeda K, Mabuchi N, Hayashi M, Tsutsui T, Ohnishi M, Sawaki, M, Fujii M, Matsumoto T, Matsui T, Kinoshita M. Effect of spironolactone on plasma brain natriuretic peptide and left ventricular remodeling in patients with congestive heart failure. J Am Coll Cardiol 2001;37:1228–1233.
Cicoira M, Zanolla L, Rossi A, Golia G, Franeschini L, Brighetti G, Marino P, Zardini P. Long-term, dose dependent effects of spironolactone on left ventricular function and exercise tolerance in patients with chronic heart failure. J Am Coll Cardiol 2002;40:304–310.
MacFadyen RJ, Barr CS, Struthers AD, Aldosterone blockade reduces vascular collagen turnover, improves heart rate variability and reduces early morning rise in heart rate in heart failure patients. Cadiovasc Res 1997;35:30–34.
Meyer B, Huelsmann M, Strecker K, Neunteufl T, Pacher R, Berger R. Flow-mediated vasodilation predicts outcome in patients with chronic heart failure. JACC 2004;43:198A.
Okubo S, Niimura F, Nishimura H, Takemoto F, Fogo A, Matsusaka T, Ichikawa I. Angiotensin-independent mechanism for aldosterone synthesis during chronic extracellular fluid volume depletion. Journal of Clinical Investigation 1997:855–860.
Mazak I, Fiebler A, Dominik N, et al. Aldosterone potentiates Angiotensin II—induced signaling in vascular smooth muscle cells. Circulation 2004;109:2792–2800.
Fraccarollo D, Galuppo P, Hildemann S., Christ M, Ertl G, Baursachs J. Additive improvement of lefr ventricular remodeling and neurohormonal activation by aldosterone receptor blockade with eplerenone and ACE inhibition in rats witn myocardial infarction. JACC 2003;42:1666–1673.
Susic D, Varagic J, Ahn I, Matavelli L, Frolich ED, Eplerenone improves coronary hemodynamics and reduces cardiac fibrosis in aging spontaneously hypertensive rats. JACC 2004;43:482A.
LaColley P, Labat C, Pujol A, Delcayre C, Benetos A, Safar M. Increased carotid wall elastic modulus and fibronectin in aldosterone-salt-treated rats effects of eplerenone. Circulation 2002;106:2848–2853.
Mottram P, Haluska B, Leano R, Cowley D, Stowasser M, Marwick T. Aldosterone antagonism in hypertensive HD. Circulation 2004;110:558–565.
Pitt B, Reichek N, Willenbrock R, et al. Effect of eplerenone, enalapril, and eplerenone/enalapril in patients with essential hypertension and left ventricular hypertrophy study. Circulation 2003;108:1831–1838.
Leopold JA, Scribner AE, Dam A, Lioa R. Aldosterone impairs vascular reactivity by decreasing glucose G-phosphate dehydrogenase activity. Circ 2004;110:III–154.
Rajagopalan S, Duquaine D, King S, Pitt B, Patel P, Mineralocorticoid receptor antagonism in experimental atherosclerosis. Circulation 2002;105:2212–2216.
Keidar S, Kaplan M, Pavlotsky E, et al. Aldosterone administration to mice stimulates macrophage NADPH oxidase and increases atherosclerosis development: A possible role for angiotensin-converting enzymes and the receptors for angiotensin II and aldosterone. Circulation 2004;109:2213–2220.
Zhou Y, Chen R, Hu, et al. Angiotensin II and aldosterone are both required to stimulate atherosclerosis in apo-E deficient mice. Hyp, 2003;42:403A Abstract 83.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Pitt, B. The Role of Aldosterone Blockade in Patients with Heart Failure. Heart Fail Rev 10, 79–83 (2005). https://doi.org/10.1007/s10741-005-2352-2
Issue Date:
DOI: https://doi.org/10.1007/s10741-005-2352-2