Eplerenone: A review of its use in essential hypertension

American Journal of Cardiovascular Drugs

Volumn 5, Issue 1, 2005, Pages 51-69

  Croom, Katherine F ^a   Perry, Caroline M ^a  

^a ADIS INTERNATIONAL INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALDOSTERONE; ALDOSTERONE ANTAGONIST; AMLODIPINE; ANDROGEN RECEPTOR; ANGIOTENSIN 2 RECEPTOR ANTAGONIST; BETA ADRENERGIC RECEPTOR BLOCKING AGENT; CALCIUM CHANNEL BLOCKING AGENT; CISAPRIDE; CYCLOSPORIN; CYTOCHROME P450 3A4; DICLOFENAC; DIGOXIN; DIPEPTIDYL CARBOXYPEPTIDASE INHIBITOR; ENALAPRIL; EPLERENONE; ERYTHROMYCIN; FLUCONAZOLE; HYPERICUM PERFORATUM EXTRACT; KETOCONAZOLE; LOSARTAN; MIDAZOLAM; MINERALOCORTICOID RECEPTOR; RENIN; SAQUINAVIR; SIMVASTATIN; STEROID RECEPTOR; UNINDEXED DRUG; VASOACTIVE AGENT; VERAPAMIL; WARFARIN;

ADD ON THERAPY; ALANINE AMINOTRANSFERASE BLOOD LEVEL; ANKLE EDEMA; ANTIHYPERTENSIVE ACTIVITY; AREA UNDER THE CURVE; BINDING AFFINITY; BINDING COMPETITION; BLOOD PRESSURE REGULATION; BLOOD VESSEL; BODY WEIGHT DISORDER; BREAKTHROUGH BLEEDING; CARDIOVASCULAR DISEASE; CAUCASIAN; CLINICAL TRIAL; COUGHING; CREATININE BLOOD LEVEL; DIARRHEA; DIASTOLIC BLOOD PRESSURE; DIZZINESS; DOSE RESPONSE; DRUG ABSORPTION; DRUG APPROVAL; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG DISTRIBUTION; DRUG EFFICACY; DRUG ELIMINATION; DRUG FECES LEVEL; DRUG HALF LIFE; DRUG MECHANISM; DRUG METABOLISM; DRUG PROTEIN BINDING; DRUG RECEPTOR BINDING; DRUG STRUCTURE; DRUG TOLERABILITY; DRUG URINE LEVEL; DYSLIPIDEMIA; DYSPNEA; ENDOCRINE DISEASE; ENZYME DEFECT; EPITHELIUM; ESSENTIAL HYPERTENSION; FATIGUE; FLU LIKE SYNDROME; FOOD DRUG INTERACTION; GAMMA GLUTAMYL TRANSFERASE BLOOD LEVEL; GRAPEFRUIT JUICE; GYNECOMASTIA; HEART; HEART HYPERTROPHY; HEART INFARCTION; HEART LEFT VENTRICLE HYPERTROPHY; HEART MUSCLE FIBROSIS; HEART RATE; HORMONE BINDING; HUMAN; HYPERKALEMIA; HYPERURICEMIA; HYPOKALEMIA; HYPONATREMIA; IMPOTENCE; INCIDENCE; KIDNEY; KIDNEY DYSFUNCTION; KIDNEY FAILURE; LIVER DYSFUNCTION; MASTALGIA; MICROALBUMINURIA; MONOTHERAPY; MORBIDITY; MORTALITY; NATRIURESIS; NEGRO; NOCTURIA; NONHUMAN; OUTCOMES RESEARCH; PATIENT MONITORING; PATIENT SELECTION; PERIPHERAL EDEMA; PLASMA RENIN ACTIVITY; POLYURIA; PRIORITY JOURNAL; QUALITY OF LIFE; REVIEW; RISK MANAGEMENT; STEADY STATE; UREA NITROGEN BLOOD LEVEL; VAGINA BLEEDING; VASCULAR ENDOTHELIUM; VASCULAR FIBROSIS; VOLUNTEER; WEIGHT GAIN;

ALDOSTERONE ANTAGONISTS; ANTIHYPERTENSIVE AGENTS; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG THERAPY, COMBINATION; HUMANS; HYPERTENSION; RANDOMIZED CONTROLLED TRIALS; SPIRONOLACTONE;

EID: 12744253849     PISSN: 11753277     EISSN: None     Source Type: Journal    
DOI: 10.2165/00129784-200505010-00007     Document Type: Review

References (86)

1. Alderman M, Arakawa K, Beilin L, et al. 1999 World Health Organization - International Society of Hypertension Guidelines for the Management of Hypertension. Blood Press 1999; (8 Suppl. 1): 9-43
2. Burt VL, Whelton P, Roccella EJ, et al. Prevalence of hypertension in the US adult population: results from the Third National Health and Nutrition Survey, 1988-1991. Hypertension 1995; 25: 305-13
3. Chobanian AV, Bakris GL, Black HR, et al. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 Report. JAMA 2003 May 21; 289 (19): 2560-72
4. American Heart Association. Heart disease and stroke statistics: 2004 update [online]. Available from URL: http://www.americanheart.org [Accessed 2004 Oct 21]
5. Cha AJ, Malecha SE, Judge KW. Aldosterone: a new appreciation of its role in heart failure. Pharmacotherapy 2000; 20 (9): 1107-15
6. Rocha R, Funder JW. The pathophysiology of aldosterone in the cardiovascular system. Ann N Y Acad Sci 2002 Sep; 970: 89-100
7. Struthers AD. Aldosterone: cardiovascular assault. Am Heart J 2002 Nov; 144 (5 Suppl.): S2-7
8. Givertz MM. Manipulation of the renin-angiotensin system. Circulation 2001; 104: e14-18
9. Epstein M. Aldosterone as a mediator of progressive renal disease: pathogenetic and clinical implications. Am J Kidney Dis 2001 Apr; 37 (4): 677-88
10. Pitt B, Zannad F, Remme WJ, et al. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. N Engl J Med 1999; 341 (10): 709-17
11. McKelvie RS, Yusuf S, Pericak D, et al. Comparison of candesartan, enalapril and their combination in congestive heart failure: Randomized Evaluation of Strategies for Left Ventricular Dysfunction (RESOLVD) pilot study. RESOLVD Pilot Study Investigators. Circulation 1999; 100: 1056-64
12. de Gasparo M, Whitebread SE, Preiswerk G, et al. Antialdosterones: incidence and prevention of sexual side effects. J Steroid Biochem 1989 Jan; 32 (1B): 223-7
13. Jeuremaitre X, Chatellier G, Kreft-Jais C, et al. Efficacy and tolerance of spironolactone in essential hypertension. Am J Cardiol 1987; 60: 820-5
14. G.D. Searle LLC. Inspra™ (eplerenone) tablets. Prescribing information (US) [online]. Available from URL: http://www.inspra.com [Accessed 2004 Feb 25]
15. Quaschning T, Ruschitzka F, Shaw S, et al. Aldosterone receptor antagonism normalizes vascular function in liquorice-induced hypertension. Hypertension 2001 Feb; 37 (2 Pt 2): 801-5
16. Rocha R, Stier Jr CT, Kifor I, et al. Aldosterone: a mediator of myocardial necrosis and renal arteriopathy. Endocrinology 2000 Oct; 141 (10): 3871-8
17. Delyani JA, Robinson EL, Rudolph AE. Effect of a selective aldosterone receptor antagonist in myocardial infarction. Am J Physiol Heart Circ Physiol 2001; 50: H647-54
18. de Gasparo M, Joss U, Ramjoué HP, et al. Three new epoxy-spironolactone derivatives: characterization in vivo and in vitro. J Pharmacol Exp Ther 1987; 240 (2): 650-6
19. Weinberger MH, Roniker B, Krause SL, et al. Eplerenone, a selective aldosterone blocker, in mild-to-moderate hypertension. Am J Hypertens 2002 Aug; 15 (8): 709-16
20. Krum H, Nolly H, Workman D, et al. Efficacy of eplerenone added to renin-angiotensin blockade in hypertensive patients. Hypertension 2002 Aug; 40 (2): 117-23
21. Weinberger M, MacDonald T, Conlin PR, et al. Comparison of eplerenone and losartan in patients with low-renin hypertension [abstract no. OR-55]. Am J Hypertens 2002 Apr; 15 (4 Pt 2): 24A
22. Van Mieghem W, von Behren V, Balazovjech I, et al. Eplerenone is safe and effective as add-on therapy in hypertensive patients uncontrolled with calcium channel blockers or beta blockers [abstract no. P1163]. Eur Heart J 2002; (23 Suppl.): 211
23. Roniker B. Eplerenone: a selective antagonist of the aldosterone receptor [abstract no. 67]. Hypertension 1997 Oct; 30 (4): 995
24. Delyani JA, Rocha R, Cook CS, et al. Eplerenone: a selective aldosterone receptor antagonist (SARA). Cardiovasc Drug Rev 2001 Fall; 19 (3): 185-200
25. Frierdich G, Schuh J, Brown M, et al. Effects of the selective mineralocorticoid receptor antagonist, eplerenone, in a model of aldosterone-induced hypertension and cardiac fibrosis [abstract no. B004]. Am J Hypertens 1998 Apr; 11 (4 Pt 2): 94A
26. Rocha R, Frierdich GE, Nachowiak D, et al. Aldosterone induces a vascular inflammatory phenotype in the rat heart [abstract no. 40]. Hypertension 2001 Sep; 38 (3): 479
27. Rajagopalan S, Duquaine D, King S, et al. Mineralocorticoid receptor antagonism in experimental atherosclerosis. Circulation 2002 May 7; 105 (18): 2212-6
28. Hurlimann D, Lüscher TF, Shaw SG, et al. Eplerenone normalizes vascular function in liquorice-induced hypertension [abstract no. 3337]. Eur Heart J 2001 Sep; (22 Suppl.): 612
29. White WB, Duprez D, St Hillaire R, et al. Effects of the selective aldosterone blocker eplerenone versus the calcium antagonist amlodipine in systolic hypertension. Hypertension 2003 May; 41: 1021-6
30. Pitt B, Reichek N, Willenbrock R, et al. Effects of eplerenone, enalapril, and eplerenone/enalapril in patients with essential hypertension and left ventricular hypenrophy: the 4E-Left Ventricular Hypertrophy Study. Circulation 2003 Oct 14; 108: 1831-8
31. Williams GH, Burgess E, Kolloch RE, et al. Efficacy of eplerenone versus enalapril as monotherapy in systemic hypertension. Am J Cardiol 2004 Apr 15; 93 (8): 990-6
32. Epstein M, Buckalew Jr V, Martinez F, et al. Antiproteinuric efficacy of eplerenone, enalapril, and eplerenone/enalapril combination therapy in diabetic hypertensives with microalbuminuria [abstract no. OR-54]. Am J Hypertens 2002 Apr; 15 (4 Pt 2): 24A
33. 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 Apr 2; 41 (7): 1148-55
34. Delyani J, Myles K, Funder J. Eplerenone (SC 66110), a highly selective aldosterone antagonist [abstract no. B002]. Am J Hypertension 1998 Apr; 11 (4 Pt 2): 94A
35. Coleman CI, Reddy P, Song JC, et al. Eplerenone: the first selective aldosterone receptor antagonist for the treatment of hypertension. Formulary 2002 Oct; 37: 514-24
36. Blacher J, Amah G, Girerd X, et al. Association between increased plasma levels of aldosterone and decreased systemic arterial compliance in subjects with essential hypertension. Am J Hypertension 1997; 10: 1326-34
37. Rajagopalan S, Pitt B. Aldosterone antagonists in the treatment of hypertension and target organ damage. Curr Hypertens Rep 2001 Jun; 3 (3): 240-8
38. Barton M, d'Uscio LV, Shaw S, et al. ETA receptor blockade prevents increased tissue endothelin-1, vascular hypertrophy, and endothelial dysfunction in salt-sensitive hypertension. Hypertension 1998; 31 (Pt 2): 499-504
39. Schiffrin EL, Deng LY, Sventek P, et al. Enhanced expression of endothelin-1 gene in resistance arteries in severe human essential hypertension. J Hypertension 1997; 15 (1): 57-63
40. van Zwieten PA. Drug treatment of isolated systolic hypertension. Nephrol Dial Transplant 2001; 16 (6): 1095-7
41. Rocha R, Chander PN, Zuckerman A, et al. Role of mineralocorticoids in renal injury in stroke-prone hypertensive rats [abstract no. 49]. Hypertension 1998 Sep; 32 (3): 598
42. Cook CS, Zhang L, Fischer JS. Absorption and disposition of a selective aldosterone receptor antagonist, eplerenone, in the dog. Pharm Res 2000 Nov; 17 (11): 1426-31
43. Cook CS, Berry LM, Bible RH, et al. Pharmacokinetics and metabolism of [14C]eplerenone after oral administration to humans. Drug Metab Dispos 2003 Nov; 31 (11): 1448-55
44. Tolbert DS, Reid SE, Roniker B. Safety, tolerability, and pharmacokinetics of eplerenone, a selective aldosterone blocker [abstract no. 45]. Pharmacotherapy 2002 Oct; 22: 1331-2
45. Tolbert DS, Reid SE, Roniker B. Pharmacokinetics of eplerenone in special populations [abstract no. 46]. Pharmacotherapy 2002 Oct; 22 (10): 1332
46. Final report for evaluation of the single- and multiple-dose pharmacokinetics of eplerenone in subjects with and without renal impairment. Report no. NE3-01-06-034. US: G.D. Searle and Co., 2001 Oct 19. (Data on file)
47. Tolbert DS, Reid SE, Roniker B. Pharmacokinetics of eplerenone coadministered with other medications [abstract no. 44]. Pharmacotherapy 2002 Oct; 22 (10): 1331
48. Tolbert DS, Reid SE, Qian J, et al. Effects of erythromycin on the pharmacokinetics of eplerenone [abstract no. T2264]. AAPS PharmSci 2002; 4 (4) [online]. Available from URL: www.aapspharmaceutica.com [Accessed 2004 Nov 30]
49. Tolbert DS, Reid SE, Qian J, et al. Effects of St. John's Wort on the pharmacokinetics of eplerenone [abstract no. T2267]. AAPS PharmSci 2002; 4 (4) [online]. Available from URL: www.aapspharmaceutica.com [Accessed 2004 Nov 30]
50. Tolbert DS, Reid SE, Qian J, et al. Effects of eplerenone on the pharmacokinetics of cisapride [abstract no. T2266]. AAPS PharmSci 2002; 4 (4) [online]. Available from URL: www.aapspharmaceutica.com [Accessed 2004 Nov 30]
51. 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 Jul 1; 92 (1): 38-42
52. Saruta T, Kageyama S, Ogihara T, et al. Efficacy and safety of the selective aldosterone blocker eplerenone in Japanese patients with hypertension: a randomized, double-blind, placebo-controlled, dose-ranging study. J Clin Hypertens (Greenwich) 2004 Apr; 6 (4): 175-85
53. Burgess ED, Lacourciere Y, Ruilope-Urioste LM, et al. Long-term safety and efficacy of the selective aldosterone blocker eplerenone in patients with essential hypertension. Clin Ther 2003 Sep; 25 (9): 2388-404
54. Williams ES, Miller JM. Results from late-breaking clinical trial sessions at the American College of Cardiology 51st Annual Scientific Session. J Am Coll Cardiol 2002 Jul 3; 40 (1): 1-18
55. Final report for the evaluation of eplerenone versus losartan and placebo in black and white patients. Report no.: IE3-01-06-020. US: G.D. Searle and Co., 2001 Sep 19. (Data on file)
56. Guidelines Committee. 2003 European Society of Hypertension-European Society of Cardiology guidelines for the management of arterial hypertension. J Hypertens 2003; 21 (6): 1011-53
57. Williams B, Poulter NR, Brown MJ, et al. Guidelines for management of hypertension: report of the fourth working party of the British Hypertension Society, 2004 - BHS IV. British Hypertension Society. J Hum Hypertens 2004; 18: 139-85
58. UK Prospective Diabetes Study Group. Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. Br Med J 1998 Sep 12; 317: 703-13
59. Díez J, González A, López B, et al. Effects of antihypertensive agents on the left ventricle: clinical implications. Am J Cardiovasc Drugs 2001; 1 (4): 263-79
60. Hollenberg NK, Williams GH, Anderson R, et al. Symptoms and the distress they cause: comparison of an aldosterone antagonist and a calcium channel blocking agent in patients with systolic hypertension. Arch Intern Med 2003 Jul 14; 163 (13): 1543-8
61. Pitt B, Remme W, Zannad F, et al. Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. New Engl J Med 2003 Apr 3; 348 (14): 1309-21
62. Sica DA. Eplerenone: a new aldosterone receptor antagonist - are the FDA's restrictions appropriate? J Clin Hypertens 2002; 4 (6): 441-5
63. MacMahon S, Rodgers A. The effects of antihypertensive treatment on vascular disease: reappraisal of the evidence in 1994. J Vasc Med Biol 1993; 4 (5-6): 265-71
64. Psaty BM, Smith NL, Siscovick DS, et al. Health outcomes associated with antihypertensive therapies used as first-line agents: a systematic review and meta-analysis. JAMA 1997 Mar 5; 277 (9): 739-45
65. Moser M, Hebert PR. Prevention of disease progression, left ventricular hypertrophy and congestive heart failure in hypertension treatment trials. J Am Coll Cardiol 1996; 27: 1214-8
66. Levy D, Larson MG, Vasan RS, et al. The progression from hypertension to congestive heart failure. JAMA 1996 May 22; 275 (20): 1557-62
67. Blood pressure, cholesterol, and stroke in eastern Asia: Eastern Stroke and Coronary Heart Disease Collaborative Research Group. Lancet 1998 Dec 5; 352: 1801-7
68. Klag MJ, Whelton PK, Randall BL, et al. Blood pressure and end-stage renal disease in men. N Engl J Med 1996; 334 (1): 13-8
69. Collins R, MacMahon S. Blood pressure, antihypertensive drug treatment and the risks of stroke and of coronary heart disease. Br Med Bull 1994 Apr; 50: 272-98
70. Whitworth JA. 2003 World Health Organization (WHO)/International Society of Hypertension (ISH) statement on management of hypertension: World Health Organization International Society of Hypertension Writing Group. J Hypertens 2003; 21: 1983-92
71. Aruaz-Pacheco C, Parrott MA, Raskin P. Treatment of hypertension in adults with diabetes: American Diabetes Association. Diabetes Care 2003 Jan; (26 Suppl. 1): S80-2
72. Olivieri O, Ciacciarelli A, Signorelli D, et al. Aldosterone to renin ratio in a primary care setting: the Bussolengo Study. J Clin Endocrinol Metab 2004; 89 (9): 4221-6
73. Epstein M. Aldosterone as a determinant of cardiovascular and renal dysfunction. J R Soc Med 2001 Aug; 94 (8): 378-83
74. Rocha R, Williams GH. Rationale for the use of aldosterone antagonists in congestive heart failure. Drugs 2002; 62 (5): 723-31
75. Delyani JA. Mineralocorticoid receptor antagonists: the evolution of utility and pharmacology [genetics, pathophysiology, and pharmacological aspects]. Kidney Int 2000 Apr; 57 (4): 1408-11
76. Dahlöf B, Pennert K, Hansson L. Reversal of left ventricular hypertrophy in hypertensive patients: a metaanalysis of 109 treatment studies. Am J Hypertens 1992; 5: 95-110
77. Brown NJ, Vaughan DE. Angiotensin-converting enzyme inhibitors. Circulation 1998; 97: 1411-20
78. Toto R, Shultz P, Raij L, et al. Efficacy and tolerability of losartan in hypertensive patients with renal impairment. Hypertension 1998; 31: 684-91
79. Asmar R. Effect of antihypertensive agents on arterial stiffness as evaluated by pulse wave velocity: clinical implications. Am J Cardiovasc Drugs 2001; 1 (5): 387-97
80. Schiffrin EL. Vascular remodeling and endothelial function in hypertensive patients: effects of antihypertensive therapy. Scand Cardiovasc J 1998; (Suppl. 47): 15-21
81. Van Bortel LMAB, Kool MJF, Spek JJ. Disparate effects of antihypertensive drugs on large artery distensibility and compliance in hypertension. Am J Cardiol 1995; 76: 46E-9E
82. Cushman WC, Ford CE, Cutler JA, et al. Success and predictors of blood pressure control in diverse North American settings: the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). ALLHAT Collaborative Research Group. J Clin Hypertens 2002; 4 (6): 393-404
83. Ram CVS. Antihypertensive drugs: an overview. Am J Cardiovasc Drugs 2002; 2 (2): 77-89
84. Pitt OL, Young WF, MacDonald TM. A review of the medical treatment of primary aldosteronism. J Hypertension 2001; 19 (3): 353-61
85. Calhoun DA, Nishizaka MK, Zaman MA, et al. Hyperaldosteronism among black and white subjects with resistant hypertension. Hypertension 2002; 40: 892-6
86. Hansson L, Zanchetti A, Carruthers SG, et al. Effects of intensive blood-pressure lowering and low-dose aspirin in patients with hypertension: principal results of the Hypertension Optimal Treatment (HOT) randomised trial. HOT Study Group. Lancet 1998 Jun 13; 351: 1755-62