The Cardiovascular Effects of Eplerenone, a Selective Aldosterone-Receptor Antagonist

Clinical Therapeutics

Volumn 25, Issue 11, 2003, Pages 2647-2668

  Davis, Kelli L ^a   Nappi, Jean M ^a  

^a MEDICAL UNIVERSITY OF SOUTH CAROLINA   (United States)

Author keywords

Aldosterone receptor antagonists; Eplerenone; Heart failure; Hypertension; Renin angiotensin aldosterone system

Indexed keywords

ALDOSTERONE; ALDOSTERONE RECEPTOR; AMLODIPINE; ANGIOTENSIN RECEPTOR ANTAGONIST; ANTIHYPERTENSIVE AGENT; CYTOCHROME P450 INHIBITOR; DIPEPTIDYL CARBOXYPEPTIDASE INHIBITOR; ENALAPRIL; EPLERENONE; ERYTHROMYCIN; FLUCONAZOLE; HYDROCHLOROTHIAZIDE; KETOCONAZOLE; LOSARTAN; MINERALOCORTICOID RECEPTOR; MINERALOCORTICOID RECEPTOR BLOCKING AGENT; POTASSIUM DERIVATIVE; POTASSIUM SPARING DIURETIC AGENT; RECEPTOR BLOCKING AGENT; SAQUINAVIR; SELECTIVE ALDOSTERONE BLOCKING AGENT; SPIRONOLACTONE; UNCLASSIFIED DRUG; VERAPAMIL;

ACUTE HEART INFARCTION; ADD ON THERAPY; AGING; AREA UNDER THE CURVE; CARDIOVASCULAR DISEASE; CARDIOVASCULAR EFFECT; CLINICAL TRIAL; DIASTOLIC BLOOD PRESSURE; DOSE RESPONSE; DRUG ABSORPTION; DRUG BIOAVAILABILITY; DRUG CONTRAINDICATION; DRUG EFFICACY; DRUG ELIMINATION; DRUG METABOLISM; DRUG POTENCY; DRUG POTENTIATION; DRUG PROTEIN BINDING; DRUG RECEPTOR BINDING; DRUG STRUCTURE; DRUG TOLERABILITY; ENDOCRINE DISEASE; GYNECOMASTIA; HEART FAILURE; HEART LEFT VENTRICLE FAILURE; HUMAN; HYPERKALEMIA; HYPERLIPIDEMIA; HYPERTENSION; HYPERURICEMIA; IMPOTENCE; KIDNEY FAILURE; LIVER TOXICITY; MASTALGIA; MENSTRUATION DISORDER; MICROALBUMINURIA; MONOTHERAPY; MORBIDITY; MORTALITY; NEPHROTOXICITY; PROTEINURIA; RENIN ANGIOTENSIN ALDOSTERONE SYSTEM; REVIEW; STRUCTURE ACTIVITY RELATION; SYSTOLIC BLOOD PRESSURE;

EID: 0344664561     PISSN: 01492918     EISSN: 1879114X     Source Type: Journal    
DOI: 10.1016/S0149-2918(03)80326-0     Document Type: Article

References (49)

1. Struthers AD. Aldosterone escape during angiotensin-converting enzyme inhibitor therapy in chronic heart failure. J Card Fail. 1996;2:47-54.
2. Lee AF, MacFadyen RJ, Struthers AD. Neurohormonal reactivation in heart failure patients on chronic ACE inhibitor therapy: A longitudinal study. Eur J Heart Fail. 1999;1:401-406.
3. Cicoira M, Zanolla L, Franceschini L, et al. Relation of aldosterone "escape" despite angiotensin-converting enzyme inhibitor administration to impaired exercise capacity in chronic congestive heart failure secondary to ischemic or idiopathic dilated cardiomyopathy. Am J Cardiol. 2002;89:403-407.
4. McKelvie RS, Yusuf S, Pericak D, et al, for the RESOLVD Pilot Study Investigators. Comparison of candesartan, enalapril, and their combination in congestive heart failure: Randomized Evaluation of Strategies for Left Ventricular Dysfunction (RESOLVD) pilot study. Circulation. 1999;100:1056-1064.
5. Weber KT. Aldosterone in congestive heart failure. N Engl J Med. 2001;345:1689-1697.
6. Rocha R, Funder JW. The pathophysiology of aldosterone in the cardiovascular system. Ann N Y Acad Sci. 2002;970:89-100.
7. Rocha R, Stier CT Jr. Pathophysiological effects of aldosterone in cardiovascular tissues. Trends Endocrinol Metab. 2001;12:308-314.
8. Yusuf S, Sleight P, Pogue J, et al, for the Heart Outcomes Prevention Evaluation Study Investigators. Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high risk patients. N Engl J Med. 2000;342:145-153.
9. Parving HH, Lehnert H, Brochner-Mortensen J, et al. The effect of irbesartan on the development of diabetic nephropathy in patients with type 2 diabetes. N Engl J Med. 2001;345:870-878.
10. Brenner BM, Cooper ME, de Zeeuw D, et al. Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med. 2001;345:861-869.
11. Dahlof B, Devereux RB, Kjeldsen SE, et al. Cardiovascular morbidity and mortality in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): A randomised trial against atenolol. Lancet. 2002;359:995-1003.
12. Takeda Y, Yoneda T, Demura M, et al. Cardiac aldosterone production in genetically hypertensive rats. Hypertension. 2000;36:495-500.
13. Epstein M. Aldosterone as a determinant of cardiovascular and renal dysfunction. J R Soc Med. 2001;94:378-383.
14. Stier CT Jr, Koenig S, Lee DY, et al. Aldosterone and aldosterone antagonism in cardiovascular disease: Focus on eplerenone (Inspra). Heart Dis. 2003;5:102-118.
15. Duprez D, De Buyzere M, Rietzschel ER, Clement DL. Aldosterone and vascular damage. Curr Hypertens Rep. 2000;2:327-334.
16. Brown NJ. Eplerenone: Cardiovascular protection. Circulation. 2003;107:2512-2518.
17. Weber MA. Clinical implications of aldosterone blockade. Am Heart J. 2002;144(Suppl 5):S12-S18.
18. Rajagopalan S, Pitt B. Aldosterone antagonists in the treatment of hypertension and target organ damage. Curr Hypertens Rep. 2001;3:240-248.
19. Robert V, Silvestre JS, Charlemagne D, et al. Biological determinants of aldosterone-induced cardiac fibrosis in rats. Hypertension. 1995;26:971-978.
20. Brilla CG, Weber KT. Mineralocorticoid excess, dietary sodium, and myocardial fibrosis. J Lab Clin Med. 1992;120:893-901.
21. Brilla CG, Matsubara LS, Weber KT. Antifibrotic effects of spironolactone in preventing myocardial fibrosis in systemic arterial hypertension. Am J Cardiol. 1993;71:12A-16A.
22. Rocha R, Chander PN, Khanna K, et al. Mineralocorticoid blockade reduces vascular injury in stroke-prone hypertensive rats. Hypertension. 1998;31:451-458.
23. Rocha R, Chander PN, Zuckerman A, Stier CT Jr. Role of aldosterone in renal vascular injury in stroke-prone hypertensive rats. Hypertension. 1999;33:232-237.
24. Martinez DV, Rocha R, Matsumura M, et al. Cardiac damage prevention by eplerenone: Comparison with low sodium diet or potassium loading. Hypertension. 2002;39:614-618.
25. Pitt B, Zannad F, Remme WJ, et al, for the Randomized Aldactone Evaluation Study Investigators. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. N Engl J Med. 1999;341:709-717.
26. Farquharson CA, Struthers AD. Spironolactone increases nitric oxide bioactivity, improves endothelial vasodilator dysfunction, and suppresses vascular angiotensin I/angiotensin II conversion in patients with chronic heart failure. Circulation. 2000;101:594-597.
27. Rajagopalan S, Pitt B. Aldosterone as a target in congestive heart failure. Med Clin North Am. 2003;87:441-457.
28. Delyani JA, Rocha R, Cook CS, et al. Eplerenone: A selective aldosterone receptor antagonist (SARA). Cardiovasc Drug Rev. 2001;19:185-200.
29. de Gasparo M, Joss U, Ramjoue HP, et al. Three new epoxy-spirolactone derivatives: Characterization in vivo and in vitro. J Pharmacol Exp Ther. 1987;240:650-656.
30. Funder JW. Eplerenone, a new mineralocorticoid antagonist: In vitro and in vivo studies. Curr Opin Endocrinol Diabet. 2000;7:138-142.
31. Tolbert D, Karim A, Cook C, et al. SC-66110 (eplerenone): A selective antialdosterone antagonist. Disposition kinetics in man and identification of its major CYP450 isozyme in its biotransformation. AAPS PharmSci [serial online]. 1998;1. Abstract 1155. Available at: http://www.aapspharmsci.org/ abstracts/AM_1998/1155.html. Accessed April 2003.
32. Roniker B. Eplerenone, a selective antagonist of the aldosterone receptor. Hypertension. 1997;30:995. Abstract 67.
33. Cook CS, Berry LM, Kim DH, et al. Involvement of CYP3A in the metabolism of eplerenone in humans and dogs: Differential metabolism by CYP3A4 and CYP3A5. Drug Metab Dispos. 2002;30:1344-1351.
34. Weinberger MH, Roniker B, Krause SL, Weiss RJ. Eplerenone, a selective aldosterone blocker, in mild-to-moderate hypertension. Am J Hypertens. 2002;15:709-716.
35. Krum H, Nolly H, Workman D, et al. Efficacy of eplerenone added to renin-angiotensin blockade in hypertensive patients. Hypertension. 2002;40:117-123.
36. Flack JM, Oparil S, Pratt JH, et al. Efficacy and tolerability of eplerenone and losartan in hypertensive black and white patients. J Am Coll Cardiol. 2003;41:1148-1155.
37. White WB, Carr AA, Krause S, et al. Assessment of the novel selective aldosterone blocker eplerenone using ambulatory and clinical blood pressure in patients with systemic hypertension. Am J Cardiol. 2003;92:38-42.
38. Burgess E, Niegowska J, Tan KW, et al. Antihypertensive effects of eplerenone and enalapril in patients with essential hypertension. Am J Hypertens. 2002;15:23A. Abstract OR-51.
39. Weinberger M, MacDonald T, Conlin PR, et al. Comparison of eplerenone and losartan in patients with low-renin hypertension. Am J Hypertens. 2002;15:24A. Abstract OR-55.
40. White WB, Lewin AJ, Nestel P, et al. Comparison of selective aldosterone blockade versus calcium antagonism on blood pressure, vascular compliance, and microalbuminuria in systolic hypertension in older people. Am J Hypertens. 2002;15:23A. Abstract OR-52.
41. Pitt B, Remme W, Zannad F, et al. Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med. 2003;348:1309-1321.
42. Pitt B, Reichek B, Metscher B, et al. Efficacy and safety of eplerenone, enalapril, and eplerenone/enalapril combination therapy in patients with left ventricular hypertrophy. Am J Hypertens. 2002;15:23A-24A. Abstract OR-53.
43. Epstein M, Buckalew V, Martinez F, et al. Antiproteinuric efficacy of eplerenone, enalapril, and eplerenone/enalapril combination therapy in diabetic hypertensives with microalbuminuria. Am J Hypertens. 2002;15:24A. Abstract OR-54.
44. Muiesan ML, Rizzoni D, Salvetti M, et al. Structural changes in small resistance arteries and left ventricular geometry in patients with primary and secondary hypertension. J Hypertens. 2002;20:1439-1444.
45. Devereux RB. Therapeutic options in minimizing left ventricular hypertrophy. Am Heart J. 2000;139:S9-S14.
46. Inspra [package insert]. New York: Pfizer Inc; 2003.
47. Sica DA. Eplerenone: A new aldosterone receptor antagonist - are the FDA's restrictions appropriate? J Clin Hypertens (Greenwich). 2002;4:441-445.
48. Burgess E, Lacourciere Y, Puopolo A, et al. The selective aldosterone blocker eplerenone is safe and efficacious for the long-term treatment of mild-to-moderate hypertension. Am J Hypertens. 2002;15:57A-58A. Abstract P-70.
49. Tolbert DS, Karim A, Nasafi J, et al. Eplerenone biotransformation: Ketoconazole but not fluconazole substantially increases eplerenone exposure in man. AAPS PharmSci [serial online]. 2000;2. Abstract 1814. Available at: http://www.aapspharmaceutica.com/search/abstract_view.asp?id-3268&ct- 00Abstracts. Accessed April 2003.