A randomized controlled study of finerenone vs. eplerenone in Japanese patients with worsening chronic heart failure and diabetes and/or chronic kidney disease

Circulation Journal

Volumn 80, Issue 5, 2016, Pages 1113-1122

  Sato, Naoki ^a   Ajioka, Masayoshi ^b   Yamada, Takahisa ^c   Kato, Masaharu ^d   Myoishi, Masafumi ^d   Yamada, Takashi ^d   Kim, So Young ^e   Nowack, Christina ^e   Kolkhof, Peter ^f   Shiga, Tsuyoshi ^g,h  

^a NIPPON MEDICAL SCHOOL MUSASHI KOSUGI HOSPITAL   (Japan)

^b TOSEI GENERAL HOSPITAL   (Japan)

^c OSAKA GENERAL MEDICAL CENTER   (Japan)

^d BAYER YAKUHIN LTD   (Japan)

^e Otsuka Pharmaceutical Development and Commercialization   (Japan)

^f Global Drug Discovery   (Japan)

^g BAYER PHARMA AG   (Germany)

^h TOKYO WOMEN'S MEDICAL UNIVERSITY   (Japan)

Author keywords

Finerenone; Japanese; Mineralocorticoid receptor antagonists; Worsening heart failure

Indexed keywords

EPLERENONE; FINERENONE; BRAIN NATRIURETIC PEPTIDE; NAPHTHYRIDINE DERIVATIVE; PEPTIDE FRAGMENT; PRO-BRAIN NATRIURETIC PEPTIDE (1-76); SPIRONOLACTONE;

AGED; ARTICLE; CHRONIC KIDNEY DISEASE; CHRONIC KIDNEY FAILURE; CONTROLLED STUDY; DIABETES MELLITUS; DOUBLE BLIND PROCEDURE; DRUG DOSE INCREASE; DRUG DOSE TITRATION; DRUG WITHDRAWAL; EVALUATION AND FOLLOW UP; FEMALE; GLUCOSE BLOOD LEVEL; HEART EJECTION FRACTION; HEART FAILURE; HOSPITALIZATION; HUMAN; HYPERKALEMIA; HYPOTENSION; MAJOR CLINICAL STUDY; MALE; MODERATE RENAL IMPAIRMENT; OUTCOME ASSESSMENT; PHASE 2 CLINICAL TRIAL; POTASSIUM BLOOD LEVEL; QUALITY OF LIFE ASSESSMENT; QUESTIONNAIRE; RANDOMIZED CONTROLLED TRIAL; RISK ASSESSMENT; SYSTOLIC BLOOD PRESSURE; TREATMENT DURATION; ADULT; ANALOGS AND DERIVATIVES; BLOOD; CHEMICALLY INDUCED; CHRONIC DISEASE; CLINICAL TRIAL; COMPLICATION; JAPAN; PATIENT SAFETY; RENAL INSUFFICIENCY, CHRONIC;

ADULT; CHRONIC DISEASE; DIABETES MELLITUS; DOUBLE-BLIND METHOD; HEART FAILURE; HUMANS; HYPERKALEMIA; JAPAN; NAPHTHYRIDINES; NATRIURETIC PEPTIDE, BRAIN; PATIENT SAFETY; PEPTIDE FRAGMENTS; RENAL INSUFFICIENCY, CHRONIC; SPIRONOLACTONE;

EID: 84964253003     PISSN: 13469843     EISSN: 13474820     Source Type: Journal    
DOI: 10.1253/circj.CJ-16-0122     Document Type: Article

References (43)

1. Japanese Circulation Society. Guidelines for treatment of chronic heart failure. http://www.j-circ.or.jp/guideline/pdf/JCS2010_matsuzaki_h.pdf (in Japanese).
2. 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: Randomized Aldactone Evaluation Study Investigators. N Engl J Med 1999; 341: 709–717.
3. Zannad F, McMurray JJ, Krum H, van Veldhuisen DJ, Swedberg K, Shi H, et al. Eplerenone in patients with systolic heart failure and mild symptoms. N Engl J Med 2011; 364: 11–21.
4. McMurray JJ, Adamopoulos S, Anker SD, Auricchio A, Bohm M, Dickstein K, et al. ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2012: The Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2012 of the European Society of Cardiology: Developed in collaboration with the Heart Failure Association (HFA) of the ESC. Eur Heart J 2012; 33: 1787–1847.
5. Yancy CW, Jessup M, Bozkurt B, Butler J, Casey DE Jr, Drazner MH, et al. 2013 ACCF/AHA guideline for the management of heart failure: Executive summary: A report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines. Circulation 2013; 128: 1810–1852.
6. Komajda M. Current challenges in the management of heart failure. Circ J 2015; 79: 948–953.
7. Juurlink DN, Mamdani MM, Lee DS, Kopp A, Austin PC, Laupacis A, et al. Rates of hyperkalemia after publication of the Randomized Aldactone Evaluation Study. N Engl J Med 2004; 351: 543–551.
8. Eschalier R, McMurray JJ, Swedberg K, van Veldhuisen DJ, Krum H, Pocock SJ, et al. Safety and efficacy of eplerenone in patients at high risk for hyperkalemia and/or worsening renal function: Analyses of the EMPHASIS-HF study subgroups (Eplerenone in Mild Patients Hospitalization And SurvIval Study in Heart Failure). J Am Coll Cardiol 2013; 62: 1585–1593.
9. Albert NM, Yancy CW, Liang L, Zhao X, Hernandez AF, Peterson ED, et al. Use of aldosterone antagonists in heart failure. JAMA 2009; 302: 1658–1665.
10. Bärfacker L, Kuhl A, Hillisch A, Grosser R, Figueroa-Perez S, Heckroth H, et al. Discovery of BAY 94-8862: A nonsteroidal antagonist of the mineralocorticoid receptor for the treatment of cardiorenal diseases. Chem Med Chem 2012; 7: 1385–1403.
11. Amazit L, Le Billan F, Kolkhof P, Lamribet K, Viengchareun S, Fay MR, et al. Finerenone impedes aldosterone-dependent nuclear import of the mineralocorticoid receptor and prevents genomic recruitment of steroid receptor coactivator-1. J Biol Chem 2015; 290: 21876–21889.
12. Kolkhof P, Nowack C, Eitner F. Nonsteroidal antagonists of the mineralocorticoid receptor. Curr Opin Nephrol Hypertens 2015; 24: 417–424.
13. Kolkhof P, Delbeck M, Kretschmer A, Steinke W, Hartmann E, Barfacker L, et al. Finerenone, a novel selective nonsteroidal mineralocorticoid receptor antagonist protects from rat cardiorenal injury. J Cardiovasc Pharmacol 2014; 64: 69–78.
14. Pitt B, Kober L, Ponikowski P, Gheorghiade M, Filippatos G, Krum H, et al. Safety and tolerability of the novel non-steroidal mineralocorticoid receptor antagonist BAY 94-8862 in patients with chronic heart failure and mild or moderate chronic kidney disease: A randomized, double-blind trial. Eur Heart J 2013; 34: 2453–2463.
15. Filippatos G, Anker SD, Böhm M, Gheorghiade M, Køber L, Krum H, et al. A randomized controlled study of finerenone versus eplerenone in patients with worsening chronic heart failure and diabetes and/or chronic kidney disease. Eur Heart J 2016 (in press).
16. Bakris GL, Agarwal R, Chan JC, Cooper ME, Gansevoort RT, Haller H, et al. Effect of finerenone on albuminuria in patients with diabetic nephropathy: A randomized clinical trial. JAMA 2015; 314: 884–894.
17. Pitt B, Anker SD, Bohm M, Gheorghiade M, Kober L, Krum H, et al. Rationale and design of MinerAlocorticoid Receptor antagonist Tolerability Study-Heart Failure (ARTS-HF): A randomized study of finerenone vs. eplerenone in patients who have worsening chronic heart failure with diabetes and/or chronic kidney disease. Eur J Heart Fail 2015; 17: 224–232.
18. Matsuo S, Imai E, Horio M, Yasuda Y, Tomita K, Nitta K, et al. Revised equations for estimated GFR from serum creatinine in Japan. Am J Kidney Dis 2009; 53: 982–992.
19. Pitt B, Remme W, Zannad F, Neaton J, Martinez F, Roniker B, et al. Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med 2003; 348: 1309–1321.
20. Girerd N, Pang PS, Swedberg K, Fought A, Kwasny MJ, Subacius H, et al. Serum aldosterone is associated with mortality and re-hospitalization in patients with reduced ejection fraction hospitalized for acute heart failure: Analysis from the EVEREST trial. Eur J Heart Fail 2013; 15: 1228–1235.
21. Ushigome R, Sakata Y, Nochioka K, Miyata S, Miura M, Tadaki S, et al. Temporal trends in clinical characteristics, management and prognosis of patients with symptomatic heart failure in Japan: Report from the CHART Studies. Circ J 2015; 79: 2396–2407.
22. Parikh KS, Felker GM, Metra M. Mode of death after acute heart failure hospitalization: A clue to possible mechanisms. Circ J 2016; 80: 17–23.
23. Lentini S, Heinig R, Kimmeskamp-Kirschbaum N, Wensing G. Pharmacokinetics, safety and tolerability of the novel, selective mineralocorticoid receptor antagonist finerenone: Results from first-inman and relative bioavailability studies. Fundam Clin Pharmacol 2016; 30: 172–184.
24. Sarma S, Mentz RJ, Kwasny MJ, Fought AJ, Huffman M, Subacius H, et al. Association between diabetes mellitus and post-discharge outcomes in patients hospitalized with heart failure: Findings from the EVEREST trial. Eur J Heart Fail 2013; 15: 194–202.
25. Vardeny O, Wu DH, Desai A, Rossignol P, Zannad F, Pitt B, et al. Influence of baseline and worsening renal function on efficacy of spironolactone in patients With severe heart failure: Insights from RALES (Randomized Aldactone Evaluation Study). J Am Coll Cardiol 2012; 60: 2082–2089.
26. Pitt B, Bakris G, Ruilope LM, DiCarlo L, Mukherjee R. Serum potassium and clinical outcomes in the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS). Circulation 2008; 118: 1643–1650.
27. Yamaji M, Tsutamoto T, Kawahara C, Nishiyama K, Yamamoto T, Fujii M, et al. Serum cortisol as a useful predictor of cardiac events in patients with chronic heart failure: The impact of oxidative stress. Circ Heart Fail 2009; 2: 608–615.
28. Yamaji M, Tsutamoto T, Kawahara C, Nishiyama K, Yamamoto T, Fujii M, et al. Effect of eplerenone versus spironolactone on cortisol and hemoglobin A1(c) levels in patients with chronic heart failure. Am Heart J 2010; 160: 915–921.
29. Pitt B, Anker SD, Bushinsky DA, Kitzman DW, Zannad F, Huang IZ. Evaluation of the efficacy and safety of RLY5016, a polymeric potassium binder, in a double-blind, placebo-controlled study in patients with chronic heart failure (the PEARL-HF) trial. Eur Heart J 2011; 32: 820–828.
30. Electronic Medicines Compendium (emc). Eplerenone 25 mg filmcoated tablets [SPC]. https://www.medicines.org.uk/emc/medicine/29837 (accessed March 25, 2016).
31. Pascual-Figal DA, Domingo M, Casas T, Gich I, Ordonez-Llanos J, Martinez P, et al. Usefulness of clinical and NT-proBNP monitoring for prognostic guidance in destabilized heart failure outpatients. Eur Heart J 2008; 29: 1011–1018.
32. Verdiani V, Ognibene A, Rutili MS, Lombardo C, Bacci F, Terreni A, et al. NT-ProBNP reduction percentage during hospital stay predicts long-term mortality and readmission in heart failure patients. J Cardiovasc Med (Hagerstown) 2008; 9: 694–699.
33. Bettencourt P, Azevedo A, Pimenta J, Frioes F, Ferreira S, Ferreira A. N-terminal-pro-brain natriuretic peptide predicts outcome after hospital discharge in heart failure patients. Circulation 2004; 110: 2168–2174.
34. Berry C, Murphy NF, De Vito G, Galloway S, Seed A, Fisher C, et al. Effects of aldosterone receptor blockade in patients with mildmoderate heart failure taking a beta-blocker. Eur J Heart Fail 2007; 9: 429–434.
35. Frantz RP, Olson LJ, Grill D, Moualla SK, Nelson SM, Nobrega TP, et al. Carvedilol therapy is associated with a sustained decline in brain natriuretic peptide levels in patients with congestive heart failure. Am Heart J 2005; 149: 541–547.
36. Fruhwald FM, Fahrleitner-Pammer A, Berger R, Leyva F, Freemantle N, Erdmann E, et al. Early and sustained effects of cardiac resynchronization therapy on N-terminal pro-B-type natriuretic peptide in patients with moderate to severe heart failure and cardiac dyssynchrony. Eur Heart J 2007; 28: 1592–1597.
37. Hartmann F, Packer M, Coats AJ, Fowler MB, Krum H, Mohacsi P, et al. Prognostic impact of plasma N-terminal pro-brain natriuretic peptide in severe chronic congestive heart failure: A substudy of the Carvedilol Prospective Randomized Cumulative Survival (COPERNICUS) trial. Circulation 2004; 110: 1780–1786.
38. Iraqi W, Rossignol P, Angioi M, Fay R, Nuee J, Ketelslegers JM, et al. Extracellular cardiac matrix biomarkers in patients with acute myocardial infarction complicated by left ventricular dysfunction and heart failure: Insights from the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS) study. Circulation 2009; 119: 2471–2479.
39. Maggioni AP, Anand I, Gottlieb SO, Latini R, Tognoni G, Cohn JN. Effects of valsartan on morbidity and mortality in patients with heart failure not receiving angiotensin-converting enzyme inhibitors. J Am Coll Cardiol 2002; 40: 1414–1421.
40. Tsutamoto T, Wada A, Maeda K, Mabuchi N, Hayashi M, Tsutsui T, et al. 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.
41. Udelson JE, Feldman AM, Greenberg B, Pitt B, Mukherjee R, Solomon HA, et al. Randomized, double-blind, multicenter, placebocontrolled study evaluating the effect of aldosterone antagonism with eplerenone on ventricular remodeling in patients with mild-to-moderate heart failure and left ventricular systolic dysfunction. Circ Heart Fail 2010; 3: 347–353.
42. Hamm CW, Bassand JP, Agewall S, Bax J, Boersma E, Bueno H, et al. ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: The Task Force for the management of acute coronary syndromes (ACS) in patients presenting without persistent ST-segment elevation of the European Society of Cardiology (ESC). Eur Heart J 2011; 32: 2999–3054.
43. Wright RS, Anderson JL, Adams CD, Bridges CR, Casey DE Jr, Ettinger SM, et al. 2011 ACCF/AHA Focused Update of the Guidelines for the Management of Patients With Unstable Angina/ Non- ST-Elevation Myocardial Infarction (Updating the 2007 Guideline): A report of the American College of Cardiology Foundation/ American Heart Association Task Force on Practice Guidelines. Circulation 2011; 123: 2022–2060.