Rationale and design of ARTS: A randomized, double-blind study of BAY 94-8862 in patients with chronic heart failure and mild or moderate chronic kidney disease

European Journal of Heart Failure

Volumn 14, Issue 6, 2012, Pages 668-675

  Pitt, Bertram ^a   Filippatos, Gerasimos ^b   Gheorghiade, Mihai ^c   Kober, Lars ^d   Krum, Henry ^e   Ponikowski, Piotr ^f   Nowack, Christina ^g   Kolkhof, Peter ^g   Kim, So Young ^g   Zannad, Faiez ^h  

^a UNIVERSITY OF MICHIGAN MEDICAL SCHOOL   (United States)

^b NATIONAL AND KAPODISTRIAN UNIVERSITY OF ATHENS   (Greece)

^c NORTHWESTERN UNIVERSITY   (United States)

^d UNIVERSITY OF COPENHAGEN   (Denmark)

^e MONASH UNIVERSITY   (Australia)

^f WROCLAW MEDICAL UNIVERSITY   (Poland)

^g BAYER PHARMA AG   (Germany)

^h UNIVERSITY HOSPITAL OF NANCY   (France)

Author keywords

Aldosterone; Antagonist; Chronic kidney disease; Heart failure; Mineralocorticoid receptor

Indexed keywords

ANDROGEN RECEPTOR; BAY 948862; EPLERENONE; ESTROGEN RECEPTOR ALPHA; ESTROGEN RECEPTOR BETA; GLUCOCORTICOID RECEPTOR; HORMONE RECEPTOR BLOCKING AGENT; MINERALOCORTICOID RECEPTOR; PLACEBO; POTASSIUM; PROGESTERONE RECEPTOR; SPIRONOLACTONE; UNCLASSIFIED DRUG;

ALBUMINURIA; ARTICLE; CHRONIC KIDNEY DISEASE; CONTROLLED STUDY; DOUBLE BLIND PROCEDURE; DRUG SAFETY; GLOMERULUS FILTRATION RATE; HEART FAILURE; HEART LEFT VENTRICLE EJECTION FRACTION; HUMAN; KIDNEY FUNCTION; MULTICENTER STUDY; POTASSIUM BLOOD LEVEL; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL;

ALDOSTERONE; ALDOSTERONE ANTAGONISTS; CONFIDENCE INTERVALS; DOUBLE-BLIND METHOD; FEMALE; HEALTH STATUS INDICATORS; HEART FAILURE; HUMANS; KIDNEY FAILURE, CHRONIC; MALE; RECEPTORS, MINERALOCORTICOID; RESEARCH DESIGN; SEVERITY OF ILLNESS INDEX; SPIRONOLACTONE;

EID: 84861563400     PISSN: 13889842     EISSN: 18790844     Source Type: Journal    
DOI: 10.1093/eurjhf/hfs061     Document Type: Article

References (29)

1. Gheorghiade M, Pang PS, Ambrosy AP, Lan G, Schmidt P, Filippatos G, Konstam M, Swedberg K, Cook T, Traver B, Maggioni A, Burnett J, Grinfeld L, Udelson J, Zannad F. A comprehensive, longitudinal description of the in-hospital and post-discharge clinical, laboratory, and neurohormonal course of patients with heart failure who die or are re-hospitalized within 90 days: analysis from the EVEREST trial. Heart Fail Rev 2012;17:485-509.
2. McMurray JJ. CONSENSUS to EMPHASIS: the overwhelming evidence which makes blockade of the renin-angiotensin-aldosterone system the cornerstone of therapy for systolic heart failure. Eur J Heart Fail 2011;13:929-936.
3. Pitt B, RemmeW, Zannad F, Neaton J, Martinez F, Roniker B, Bittman R, Hurley S, Kleiman J, Gatlin M. Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med 2003;348: 1309-1321.
4. Pitt B, Zannad F, Remme WJ, Cody R, Castaigne A, Perez A, Palensky J, Wittes J. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. N Engl J Med 1999;341:709-717.
5. Zannad F, McMurray JJ, Krum H, van Veldhuisen DJ, Swedberg K, Shi H, Vincent J, Pocock SJ, Pitt B. Eplerenone in patients with systolic heart failure and mild symptoms. N Engl J Med 2011;364:11-21.
6. Funder JW, Carey RM, Fardella C, Gomez-Sanchez CE, Mantero F, Stowasser M, Young WF Jr, Montori VM. Case detection, diagnosis, and treatment of patients with primary aldosteronism: an endocrine society clinical practice guideline. J Clin Endocrinol Metab 2008;93:3266-3281.
7. Epstein M, Calhoun DA. Aldosterone blockers (mineralocorticoid receptor antagonism) and potassium-sparing diuretics. J Clin Hypertens (Greenwich) 2011;13: 644-648.
8. Bianchi S, Bigazzi R, Campese VM. Long-term effects of spironolactone on proteinuria and kidney function in patients with chronic kidney disease. Kidney Int 2006;70:2116-2123.
9. Bomback AS, Kshirsagar AV, Amamoo MA, Klemmer PJ. Change in proteinuria after adding aldosterone blockers to ACE inhibitors or angiotensin receptor blockers in CKD: a systematic review. Am J Kidney Dis 2008;51:199-211.
10. Jain G, Campbell RC, Warnock DG. Mineralocorticoid receptor blockers and chronic kidney disease. Clin J Am Soc Nephrol 2009;4:1685-1691.
11. Navaneethan SD, Nigwekar SU, Sehgal AR, Strippoli GF. Aldosterone antagonists for preventing the progression of chronic kidney disease. Cochrane Database Syst Rev 2009(3):CD007004.
12. Kosmala W, Przewlocka-Kosmala M, Szczepanik-Osadnik H, Mysiak A, O'Moore-Sullivan T, Marwick TH. A randomized study of the beneficial effects of aldosterone antagonism on LV function, structure, and fibrosis markers in metabolic syndrome. JACC Cardiovasc Imaging 2011;4:1239-1249.
13. Albert NM, Yancy CW, Liang L, Zhao X, Hernandez AF, Peterson ED, Cannon CP, Fonarow GC. Use of aldosterone antagonists in heart failure. JAMA 2009;302:1658-1665.
14. Fonarow GC, Yancy CW, Albert NM, Curtis AB, Stough WG, Gheorghiade M, Heywood JT, McBride ML, Mehra MR, O'Connor CM, Reynolds D, Walsh MN. Heart failure care in the outpatient cardiology practice setting: findings from IMPROVE HF. Circ Heart Fail 2008;1:98-106.
15. Maggioni AP, Dahlstrom U, Filippatos G, Chioncel O, Leiro MC, Drozdz J, Fruhwald F, Gullestad L, Logeart D, Metra M, Parissis J, Persson H, Ponikowski P, Rauchhaus M, Voors A, Nielsen OW, Zannad F, Tavazzi L. EURObservational Research Programme: the Heart Failure Pilot Survey (ESC-HF Pilot). Eur J Heart Fail 2010;12:1076-1084.
16. Corvol P, Michaud A, Menard J, Freifeld M, Mahoudeau J. Antiandrogenic effect of spirolactones: mechanism of action. Endocrinology 1975;97:52-58.
17. Weber KT. Aldosterone in congestive heart failure. N Engl J Med 2001;345: 1689-1697.
18. Jackson EK. Diuretics. In: Hardman JG, Limbird LE (eds). Goodman & Gilman's: The Pharmacological Basis of Therapeutics. 10th ed. New York: McGraw-Hill; 2001. p780-781.
19. 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.
20. Parthasarathy HK, Menard J, White WB, Young WF Jr, Williams GH, Williams B, Ruilope LM, McInnes GT, Connell JM, MacDonald TM. A double-blind, randomized study comparing the antihypertensive effect of eplerenone and spironolactone in patients with hypertension and evidence of primary aldosteronism. J Hypertens 2011;29:980-990.
21. Funder JW. Mineralocorticoid-receptor blockade, hypertension and heart failure. Nat Clin Pract Endocrinol Metab 2005;1:4-5.
22. Kolkhof P, Borden SA. Molecular pharmacology of the mineralocorticoid receptor: prospects for novel therapeutics. Mol Cell Endocrinol 2012;350:310-317.
23. Albaghdadi M, Gheorghiade M, Pitt B. Mineralocorticoid receptor antagonism: therapeutic potential in acute heart failure syndromes. Eur Heart J 2011;32: 2626-2633.
24. Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D. A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study Group. Ann Intern Med 1999;130:461-170.
25. Fagart J, Hillisch A, Huyet J, Barfacker L, Fay M, Pleiss U, Pook E, Schafer S, Rafestin-Oblin ME, Kolkhof P. A new mode of mineralocorticoid receptor antagonism by a potent and selective nonsteroidal molecule. J Biol Chem 2010;285: 29932-29940.
26. Bärfacker L, Kuhl A, Hillisch A, Grosser R, Figueroa-Pérez S, Heckroth H, Nitsche A, Ergüden JK, Gielen-Haertwig H, Schlemmer KH, Mittendorf J, Paulsen H, Platzek J, Kolkhof P. Discovery of BAY 94-8862: a non-steroidal antagonist of the mineralocorticoid receptor for the treatment of cardiorenal diseases. ChemMedChem 2012; in press.
27. Arhancet GB, Woodard SS, Dietz JD, Garland DJ, Wagner GM, Iyanar K, Collins JT, Blinn JR, Numann RE, Hu X, Huang HC. Stereochemical requirements for the mineralocorticoid receptor antagonist activity of dihydropyridines. J Med Chem 2010;53:4300-4304.
28. Dietz JD, Du S, Bolten CW, Payne MA, Xia C, Blinn JR, Funder JW, Hu X. A number of marketed dihydropyridine calcium channel blockers have mineralocorticoid receptor antagonist activity. Hypertension 2008;51:742-748.
29. Einhorn LM, Zhan M, Hsu VD, Walker LD, Moen MF, Seliger SL, Weir MR, Fink JC. The frequency of hyperkalemia and its significance in chronic kidney disease. Arch Intern Med 2009;169:1156-1162.