spironolactone and Disease Exacerbation studies

Spironolactone: A potassium sparing diuretic that acts by antagonism of aldosterone in the distal renal tubules. It is used mainly in the treatment of refractory edema in patients with congestive heart failure, nephrotic syndrome, or hepatic cirrhosis. Its effects on the endocrine system are utilized in the treatments of hirsutism and acne but they can lead to adverse effects. (From Martindale, The Extra Pharmacopoeia, 30th ed, p827)
spironolactone : A steroid lactone that is 17alpha-pregn-4-ene-21,17-carbolactone substituted by an oxo group at position 3 and an alpha-acetylsulfanyl group at position 7.

Research Excerpts

Excerpt	Relevance	Reference
" We investigated whether the effect of spironolactone on LVDD in patients with heart failure with preserved ejection fraction (HFpEF) depends on its effects on collagen cross-linking and/or deposition."	9.27	Biomarker-based phenotyping of myocardial fibrosis identifies patients with heart failure with preserved ejection fraction resistant to the beneficial effects of spironolactone: results from the Aldo-DHF trial. ( Bach, D; Bachran, D; Delles, C; Díez, J; Dominiczak, AF; Edelmann, F; González, A; Hasenfuss, G; López, B; Pieske, B; Ravassa, S; Trippel, T; Wachter, R, 2018)
"In patients with systolic heart failure and mild symptoms, eplerenone reduced the incidence of new onset AFF."	9.16	Eplerenone and atrial fibrillation in mild systolic heart failure: results from the EMPHASIS-HF (Eplerenone in Mild Patients Hospitalization And SurvIval Study in Heart Failure) study. ( Krum, H; McMurray, JJ; Pitt, B; Shi, H; Swedberg, K; van Veldhuisen, DJ; Vincent, J; Zannad, F, 2012)
" This manuscript provides an overview of the considerations made regarding quantification of a range of clinical and economic outcomes in the EPHESUS (EPlerenone's neuroHormonal Efficacy and SUrvival Study) study, a 6200-patient, randomized, controlled trial of aldosterone blockade in patients with heart failure as a complication of acute myocardial infarction."	9.10	Expanding the outcomes in clinical trials of heart failure: the quality of life and economic components of EPHESUS (EPlerenone's neuroHormonal Efficacy and SUrvival Study). ( Deedwania, P; Hurley, S; Jones, P; Mahoney, E; Pitt, B; Poston, C; Spertus, JA; Tooley, J; Weintraub, WS, 2002)
"Spironolactone has been shown to improve outcomes in patients with heart failure (HF) with reduced ejection fraction (EF)."	7.96	Spironolactone use is associated with improved outcomes in heart failure with mid-range ejection fraction. ( Enzan, N; Higo, T; Ide, T; Kaku, H; Matsushima, S; Tsuchihashi-Makaya, M; Tsutsui, H, 2020)
"The beneficial effects of eplerenone, a specific mineralocorticoid receptor blocker, were previously demonstrated in early atherosclerosis (ATS)."	7.78	Eplerenone reduced lesion size in early but not advanced atherosclerosis in apolipoprotein E-deficient mice. ( Coleman, R; Gamliel-Lazarovich, A; Keidar, S; Raz-Pasteur, A, 2012)
"Since the Randomized Aldactone Evaluation Study (RALES), the use of spironolactone is recommended in systolic heart failure (HF) patients that have been in New York Heart Association (NYHA) class III or IV."	7.74	Safety of spironolactone use in ambulatory heart failure patients. ( Azevedo, A; Bettencourt, P; Lopes, RJ; Lourenço, AP; Mascarenhas, J, 2008)
"Hypertension was induced in adult male Cyp1a1Ren2 rats."	5.62	The effect of spironolactone on cardiac and renal fibrosis following myocardial infarction in established hypertension in the transgenic Cyp1a1Ren2 rat. ( Leader, CJ; Walker, RJ; Wilkins, GT, 2021)
"Coexistent hepatocellular carcinoma (HCC) was the only significant predictive variable that attenuated the efficacy of TLV."	5.46	Efficacy of tolvaptan for the patients with advanced hepatocellular carcinoma. ( Goya, T; Kato, M; Kohjima, M; Kotoh, K; Masumoto, A; Miyazaki, M; Motomura, K; Senjyu, T; Tanaka, K; Yada, M, 2017)
"Eplerenone is a novel selective aldosterone blocker."	5.31	Effects of long-term monotherapy with eplerenone, a novel aldosterone blocker, on progression of left ventricular dysfunction and remodeling in dogs with heart failure. ( Goldstein, S; McMahon, EG; Mishima, T; Morita, H; Rudolph, AE; Sabbah, HN; Sharov, VG; Suzuki, G; Tanhehco, EJ; Todor, A, 2002)
" We investigated whether the effect of spironolactone on LVDD in patients with heart failure with preserved ejection fraction (HFpEF) depends on its effects on collagen cross-linking and/or deposition."	5.27	Biomarker-based phenotyping of myocardial fibrosis identifies patients with heart failure with preserved ejection fraction resistant to the beneficial effects of spironolactone: results from the Aldo-DHF trial. ( Bach, D; Bachran, D; Delles, C; Díez, J; Dominiczak, AF; Edelmann, F; González, A; Hasenfuss, G; López, B; Pieske, B; Ravassa, S; Trippel, T; Wachter, R, 2018)
"In patients with systolic heart failure and mild symptoms, eplerenone reduced the incidence of new onset AFF."	5.16	Eplerenone and atrial fibrillation in mild systolic heart failure: results from the EMPHASIS-HF (Eplerenone in Mild Patients Hospitalization And SurvIval Study in Heart Failure) study. ( Krum, H; McMurray, JJ; Pitt, B; Shi, H; Swedberg, K; van Veldhuisen, DJ; Vincent, J; Zannad, F, 2012)
" The aim was to compare the effects on albuminuria of the therapy with either: (i) telmisartan 80 mg and aliskiren 300 mg, (ii) telmisartan 80 mg and eplerenone 50 mg, (iii) telmisartan 160 mg as monotherapy."	5.16	The enhanced renin-angiotensin-aldosteron system pharmacological blockade--which is the best?. ( Bednarski, R; Donderski, R; Heleniak, Z; Lizakowski, S; Manitius, J; Przybylska, M; Renke, M; Rutkowski, B; Rutkowski, P; Sulikowska, B; Tylicki, L, 2012)
"Spironolactone (25 mg/d for 8 weeks) decreased proteinuria from protein of 2."	5.11	Antagonists of aldosterone and proteinuria in patients with CKD: an uncontrolled pilot study. ( Bianchi, S; Bigazzi, R; Campese, VM, 2005)
" This manuscript provides an overview of the considerations made regarding quantification of a range of clinical and economic outcomes in the EPHESUS (EPlerenone's neuroHormonal Efficacy and SUrvival Study) study, a 6200-patient, randomized, controlled trial of aldosterone blockade in patients with heart failure as a complication of acute myocardial infarction."	5.10	Expanding the outcomes in clinical trials of heart failure: the quality of life and economic components of EPHESUS (EPlerenone's neuroHormonal Efficacy and SUrvival Study). ( Deedwania, P; Hurley, S; Jones, P; Mahoney, E; Pitt, B; Poston, C; Spertus, JA; Tooley, J; Weintraub, WS, 2002)
"To evaluate the effects of aldosterone antagonists (selective (eplerenone), non-selective (spironolactone or canrenone), or non-steroidal mineralocorticoid antagonists (finerenone)) in adults who have CKD with proteinuria (nephrotic and non-nephrotic range) on: patient-centred endpoints including kidney failure (previously know as end-stage kidney disease (ESKD)), major cardiovascular events, and death (any cause); kidney function (proteinuria, estimated glomerular filtration rate (eGFR), and doubling of serum creatinine); blood pressure; and adverse events (including hyperkalaemia, acute kidney injury, and gynaecomastia)."	5.05	Aldosterone antagonists in addition to renin angiotensin system antagonists for preventing the progression of chronic kidney disease. ( Bolignano, D; Chung, EY; Natale, P; Navaneethan, SD; Palmer, SC; Ruospo, M; Strippoli, GF, 2020)
"To evaluate the effect of aldosterone antagonists (both selective (eplerenone) and non-selective (spironolactone)) alone or in combination with ACEi or ARB in adults who have CKD with proteinuria (nephrotic and non-nephrotic range) on: patient-centred endpoints including major cardiovascular events, hospitalisation and all-cause mortality; kidney function (proteinuria, glomerular filtration rate (GFR), serum creatinine, and need for renal replacement therapy; and adverse events (including gynaecomastia and hyperkalaemia)."	4.90	Aldosterone antagonists for preventing the progression of chronic kidney disease. ( Bolignano, D; Navaneethan, SD; Palmer, SC; Strippoli, GF, 2014)
"Spironolactone has been shown to improve outcomes in patients with heart failure (HF) with reduced ejection fraction (EF)."	3.96	Spironolactone use is associated with improved outcomes in heart failure with mid-range ejection fraction. ( Enzan, N; Higo, T; Ide, T; Kaku, H; Matsushima, S; Tsuchihashi-Makaya, M; Tsutsui, H, 2020)
"Although matching aligned key demographic and clinical characteristics of the cohorts, a significantly greater proportion of spironolactone users than non-users had oedema, proteinuria, and cardiovascular disease at baseline (P < 0."	3.96	Disease characteristics and outcomes in patients with chronic kidney disease and type 2 diabetes: a matched cohort study of spironolactone users and non-users. ( Blankenburg, M; Fett, AK; Gay, A; Griner, RG; Kovesdy, CP, 2020)
" Compared with placebo, across all eGFR categories, spironolactone was associated with lower relative risk for the primary efficacy outcome and for hypokalemia, but higher relative risk for hyperkalemia, worsening renal function, and drug discontinuation."	3.91	Efficacy and Safety of Spironolactone in Patients With HFpEF and Chronic Kidney Disease. ( Beldhuis, IE; Claggett, B; Damman, K; Desai, AS; Fang, JC; Lewis, EF; Myhre, PL; O'Meara, E; Pfeffer, MA; Pitt, B; Shah, SJ; Solomon, SD; Voors, AA, 2019)
"Using a propensity score matching of 1:2 ratio, this retrospective claims database study compared spironolactone prescription (n=65) and non-spironolactone therapy (n=130) in hypertensive patients with LVH [left ventricular mass index (LVMI)>125g/m(2) for men and >110g/m(2) for women] and suspected diastolic dysfunction (E/E' ratio between 8 and 15) and without clinical signs or symptoms of heart failure."	3.83	Association between long-term prescription of aldosterone antagonist and the progression of heart failure with preserved ejection fraction in hypertensive patients. ( Bian, L; Fan, L; Fan, YQ; Gu, J; Han, ZH; Wang, CQ; Xie, YS; Xu, ZJ; Yin, ZF; Zhang, HL; Zhang, JF, 2016)
"Spironolactone induces an initial acute fall in eGFR that predicts a later favourable influence on the course of renal function and a remarkable and sustained reduction in proteinuria."	3.79	Renoprotective effects of mineralocorticoid receptor blockers in patients with proteinuric kidney diseases. ( Egido, J; Gutiérrez, E; Gutiérrez-Solís, E; Huerta, A; Millet, VG; Morales, E; Praga, M; Rojas-Rivera, J, 2013)
"The beneficial effects of eplerenone, a specific mineralocorticoid receptor blocker, were previously demonstrated in early atherosclerosis (ATS)."	3.78	Eplerenone reduced lesion size in early but not advanced atherosclerosis in apolipoprotein E-deficient mice. ( Coleman, R; Gamliel-Lazarovich, A; Keidar, S; Raz-Pasteur, A, 2012)
"Since the Randomized Aldactone Evaluation Study (RALES), the use of spironolactone is recommended in systolic heart failure (HF) patients that have been in New York Heart Association (NYHA) class III or IV."	3.74	Safety of spironolactone use in ambulatory heart failure patients. ( Azevedo, A; Bettencourt, P; Lopes, RJ; Lourenço, AP; Mascarenhas, J, 2008)
" After 4 weeks of DOCA-salt hypertension, rats were either killed (n = 6), or treated with a non-hypotensive dose of spironolactone (n = 7) or triple therapy (hydrochlorothiazide, reserpine and hydralazine, n = 8) to normalize blood pressure or with vehicle (n = 19) for two further weeks."	3.74	Blood pressure versus direct mineralocorticoid effects on kidney inflammation and fibrosis in DOCA-salt hypertension. ( Cordasic, N; Hartner, A; Hilgers, KF; Klanke, B; Schmieder, RE; Veelken, R, 2008)
"Additionally, ischemic heart disease adversely impacts the clinical course of HFrEF patients; however, its role in HFpEF is not fully understood."	3.01	Role of Ischemic Heart Disease in Major Adverse Renal and Cardiac Events Among Individuals With Heart Failure With Preserved Ejection Fraction (from the TOPCAT Trial). ( Elsaid, O; McCullough, PA; Rahimi, G; Tecson, KM, 2021)
"Of the 82 patients, 80 (88 unruptured aneurysms) were followed for a mean of 21."	2.87	Treatment of Unruptured Cerebral Aneurysms with the Mineralocorticoid Receptor Blocker Eplerenone-Pilot Study. ( Abe, T; Harada, M; Kanematsu, Y; Kinouchi, T; Kitazato, KT; Korai, M; Kuwayama, K; Matsushita, N; Miyamoto, T; Mure, H; Nagahiro, S; Nakajima, K; Okayama, Y; Satomi, J; Shimada, K; Tada, Y; Yagi, K; Yamaguchi, T, 2018)
" The ATHENA-HF (Aldosterone Targeted Neurohormonal Combined with Natriuresis Therapy in Heart Failure) trial is a randomized, double-blind, placebo-controlled study of the safety and efficacy of 100 mg/day spironolactone versus placebo (or continued low-dose spironolactone use in participants who are already receiving spironolactone at baseline) in 360 patients hospitalized for AHF."	2.82	Rationale and Design of the ATHENA-HF Trial: Aldosterone Targeted Neurohormonal Combined With Natriuresis Therapy in Heart Failure. ( Anstrom, KJ; Braunwald, E; Butler, J; Felker, GM; Hernandez, AF; Kalogeropoulos, A; Konstam, MA; Redfield, MM; Shah, MR; Tang, WH, 2016)
"19."	2.53	Mineralocorticoid Receptor Antagonists in End-Stage Renal Disease: Efficacy and Safety. ( Bomback, AS, 2016)
"Hypertension was induced in adult male Cyp1a1Ren2 rats."	1.62	The effect of spironolactone on cardiac and renal fibrosis following myocardial infarction in established hypertension in the transgenic Cyp1a1Ren2 rat. ( Leader, CJ; Walker, RJ; Wilkins, GT, 2021)
"Coexistent hepatocellular carcinoma (HCC) was the only significant predictive variable that attenuated the efficacy of TLV."	1.46	Efficacy of tolvaptan for the patients with advanced hepatocellular carcinoma. ( Goya, T; Kato, M; Kohjima, M; Kotoh, K; Masumoto, A; Miyazaki, M; Motomura, K; Senjyu, T; Tanaka, K; Yada, M, 2017)
"Spironolactone-treated mice exhibited decreased histopathologic evidence of inflammation and tissue damage, as compared with control mice."	1.35	The role of aldosterone blockade in murine lupus nephritis. ( Anderson, MR; Bradke, A; Kaplan, MJ; Killen, PD; Monrad, SU, 2008)
"Male Wistar rats fed with an unrestricted sodium diet received CsA 15 mg/kg/day or CsA at the same dosage plus 20 mg/kg/day of spironolactone."	1.35	The effect of aldosterone antagonist in experimental nephropathy induced by cyclosporine A. ( Miorin, LA; Sens, YA; Silva, FM, 2008)
"The risk of transient neonatal myasthenia gravis is relatively small but exists even when the parturient has stable MG without elevated levels of anti-acetylcholine receptor antibodies."	1.33	[Myasthenia gravis and pregnancy: clinical course and management of delivery and the postpartum phase]. ( de Seze, J; Defebvre, L; Delalande, S; Delrieu, O; Destée, A; Fourrier, F; Leys, D; Ramirez, C; Stojkovic, T; Vermersch, P, 2006)
"Thus, aldosteronism is associated with an activation of circulating immune cells induced by iterations in PBMC divalent cations and transduced by oxidative/nitrosative stress."	1.32	Aldosteronism and peripheral blood mononuclear cell activation: a neuroendocrine-immune interface. ( Ahokas, RA; Bhattacharya, SK; Gerling, IC; Herring, PA; Lu, L; Postlethwaite, AE; Sun, Y; Warrington, KJ; Weber, KT; Wodi, LA, 2003)
"Eplerenone is a novel selective aldosterone blocker."	1.31	Effects of long-term monotherapy with eplerenone, a novel aldosterone blocker, on progression of left ventricular dysfunction and remodeling in dogs with heart failure. ( Goldstein, S; McMahon, EG; Mishima, T; Morita, H; Rudolph, AE; Sabbah, HN; Sharov, VG; Suzuki, G; Tanhehco, EJ; Todor, A, 2002)
"Aldosterone promotes nephrosclerosis in several rat models, whereas aldosterone receptor antagonism blunts the effect of activation of the renin-angiotensin-aldosterone system (RAAS) on nephrosclerosis, independent of effects on blood pressure."	1.31	Aldosterone modulates plasminogen activator inhibitor-1 and glomerulosclerosis in vivo. ( Brown, NJ; Donnert, E; Fogo, AB; Freeman, M; Ma, L; Nakamura, I; Nakamura, S; Vaughan, DE, 2000)

Research

Studies (69)

Authors

Clinical Trials (26)

Trial Overview

Trial Outcomes

Aborted Cardiac Arrest

Timeframe	Studies, this research(%)	All Research%
pre-1990	0 (0.00)	18.7374
1990's	1 (1.45)	18.2507
2000's	22 (31.88)	29.6817
2010's	37 (53.62)	24.3611
2020's	9 (13.04)	2.80

Authors	Studies
Leader, CJ	1
Wilkins, GT	1
Walker, RJ	1
Gueiros, APS	1
Gueiros, JEB	1
Nóbrega, KT	1
Calado, EB	1
Matta, MCD	1
Torres, LC	1
Souza, ASR	1
Casarini, DE	1
Carvalho, AB	1
Krysiak, R	1
Kowalcze, K	1
Okopień, B	1
Enzan, N	1
Matsushima, S	1
Ide, T	1
Kaku, H	1
Higo, T	1
Tsuchihashi-Makaya, M	2
Tsutsui, H	2
Blankenburg, M	1
Kovesdy, CP	1
Fett, AK	1
Griner, RG	1
Gay, A	1
Nicholas, SB	1
Zhu, W	1
Wu, Y	1
Zhou, Y	1
Liang, W	1
Xue, R	1
Wu, Z	1
Dong, Y	1
Liu, C	1
Chung, EY	1
Ruospo, M	1
Natale, P	1
Bolignano, D	2
Navaneethan, SD	2
Palmer, SC	2
Strippoli, GF	2
Tanaka, S	1
Imamura, T	1
Ueno, H	2
Kinugawa, K	1
Rahimi, G	1
Tecson, KM	1
Elsaid, O	1
McCullough, PA	1
Miyazaki, M	1
Yada, M	1
Tanaka, K	1
Senjyu, T	1
Goya, T	1
Motomura, K	1
Kohjima, M	1
Kato, M	1
Masumoto, A	1
Kotoh, K	1
Kim, SK	1
McCurley, AT	1
DuPont, JJ	1
Aronovitz, M	1
Moss, ME	1
Stillman, IE	1
Karumanchi, SA	1
Christou, DD	1
Jaffe, IZ	1
Nagahiro, S	1
Tada, Y	1
Satomi, J	1
Kinouchi, T	1
Kuwayama, K	1
Yagi, K	1
Nakajima, K	1
Matsushita, N	1
Miyamoto, T	1
Yamaguchi, T	1
Shimada, K	1
Korai, M	1
Mure, H	1
Okayama, Y	1
Abe, T	1
Harada, M	1
Kitazato, KT	1
Kanematsu, Y	1
Ravassa, S	1
Trippel, T	1
Bach, D	1
Bachran, D	1
González, A	1
López, B	1
Wachter, R	2
Hasenfuss, G	2
Delles, C	1
Dominiczak, AF	1
Pieske, B	2
Díez, J	1
Edelmann, F	2
Barrera-Chimal, J	1
Rocha, L	1
Amador-Martínez, I	1
Pérez-Villalva, R	1
González, R	1
Cortés-González, C	1
Uribe, N	1
Ramírez, V	1
Berman, N	1
Gamba, G	1
Bobadilla, NA	1
Dhondt, B	1
Buelens, S	1
Van Besien, J	1
Beysens, M	1
De Bleser, E	1
Ost, P	1
Lumen, N	1
Beldhuis, IE	1
Myhre, PL	1
Claggett, B	1
Damman, K	1
Fang, JC	1
Lewis, EF	1
O'Meara, E	1
Pitt, B	4
Shah, SJ	1
Voors, AA	1
Pfeffer, MA	2
Solomon, SD	1
Desai, AS	1
Kurobe, H	1
Hirata, Y	1
Matsuoka, Y	1
Sugasawa, N	1
Higashida, M	1
Nakayama, T	1
Maxfield, MW	1
Yoshida, Y	1
Shimabukuro, M	1
Kitagawa, T	1
Sata, M	1
Ferreira, JP	1
Santos, M	1
Almeida, S	1
Marques, I	1
Bettencourt, P	2
Carvalho, H	1
Carillo, S	1
Zhang, Y	1
Fay, R	1
Angioi, M	1
Vincent, J	2
Sutradhor, SC	1
Ahmed, A	1
Zannad, F	2
Hill, NR	1
Lasserson, D	1
Thompson, B	1
Perera-Salazar, R	1
Wolstenholme, J	1
Bower, P	1
Blakeman, T	1
Fitzmaurice, D	1
Little, P	1
Feder, G	1
Qureshi, N	1
Taal, M	1
Townend, J	1
Ferro, C	1
McManus, R	1
Hobbs, FR	1
Jeewandara, TM	1
Ameer, OZ	1
Boyd, R	1
Wyse, BF	1
Underwood, CF	1
Phillips, JK	1
Mody, KP	1
Lyons, JJ	1
Jorde, UP	1
Uriel, N	1
Hou, J	1
Xiong, W	1
Cao, L	1
Wen, X	1
Li, A	1
Tatsumoto, N	1
Yamada, S	2
Tokumoto, M	1
Eriguchi, M	1
Noguchi, H	1
Torisu, K	1
Tsuruya, K	1
Kitazono, T	1
Wang, S	1
Li, B	1
Li, C	1
Cui, W	1
Miao, L	1
Bomback, AS	1
Gu, J	1
Fan, YQ	1
Han, ZH	1
Fan, L	1
Bian, L	1
Zhang, HL	1
Xu, ZJ	1
Yin, ZF	1
Xie, YS	1
Zhang, JF	1
Wang, CQ	1
Butler, J	1
Hernandez, AF	1
Anstrom, KJ	1
Kalogeropoulos, A	1
Redfield, MM	2
Konstam, MA	1
Tang, WH	1
Felker, GM	1
Shah, MR	1
Braunwald, E	1
Sedhom, R	1
Hu, S	1
Ohri, A	1
Infantino, D	1
Lubitz, S	1
Klanke, B	1
Cordasic, N	1
Hartner, A	1
Schmieder, RE	1
Veelken, R	1
Hilgers, KF	1
Silva, FM	1
Miorin, LA	1
Sens, YA	1
Yoshimura, M	1
Nakayama, M	1
Yamamuro, M	1
Nishijima, T	1
Kusuhara, K	1
Nagayoshi, Y	1
Kojima, S	1
Kaikita, K	1
Sumida, H	1
Sugiyama, S	1
Ogawa, H	1
Lopes, RJ	1
Lourenço, AP	1
Mascarenhas, J	1
Azevedo, A	1
Barison, A	1
Aquaro, GD	1
Passino, C	1
Falorni, M	1
Balbarini, A	1
Lombardi, M	1
Pasquali, L	1
Emdin, M	1
Siciliano, G	1
Ku, E	1
Campese, VM	3
Hou, W	1
Sanyal, AJ	1
Guney, I	1
Selcuk, NY	1
Altintepe, L	1
Atalay, H	1
Başarali, MK	1
Büyükbaş, S	1
Bianchi, S	2
Bigazzi, R	2
Gkizas, SI	1
Apostolakis, E	1
Pagoulatou, E	1
Mavrilas, D	1
Papachristou, DJ	1
Koletsis, E	1
Papalois, A	1
Papadaki, H	1
Alexopoulos, D	1
Vukusich, A	1
Kunstmann, S	1
Varela, C	1
Gainza, D	1
Bravo, S	1
Sepulveda, D	1
Cavada, G	1
Michea, L	1
Marusic, ET	1
Schmidt, AG	1
Gelbrich, G	1
Binder, L	1
Herrmann-Lingen, C	1
Halle, M	1
Hamaguchi, S	1
Kinugawa, S	1
Goto, K	1
Goto, D	1
Yokota, T	1
Yokoshiki, H	1
Takeshita, A	1
Lauten, A	1
Ferrari, M	1
Goebel, B	1
Rademacher, W	1
Schumm, J	1
Uth, O	1
Kiehntopf, M	1
Figulla, HR	1
Jung, C	1
Lian, M	1
Hewitson, TD	1
Wigg, B	1
Samuel, CS	1
Chow, F	1
Becker, GJ	1
Zhou, X	1
Crook, MF	1
Sharif-Rodriguez, W	1
Zhu, Y	1
Ruben, Z	1
Pan, Y	1
Urosevic-Price, O	1
Wang, L	1
Flattery, AM	1
Forrest, G	1
Szeto, D	1
Zhao, H	1
Roy, S	1
Forrest, MJ	1
Iwazu, Y	1
Muto, S	1
Hirahara, I	1
Fujisawa, G	1
Takeda, S	1
Kusano, E	1
Swedberg, K	2
McMurray, JJ	2
Krum, H	1
van Veldhuisen, DJ	1
Shi, H	1
Weber, MA	1
Nagel, AM	1
Wolf, MB	1
Jurkat-Rott, K	1
Kauczor, HU	1
Semmler, W	1
Lehmann-Horn, F	1
Morales, E	1
Millet, VG	1
Rojas-Rivera, J	1
Huerta, A	1
Gutiérrez, E	1
Gutiérrez-Solís, E	1
Egido, J	1
Praga, M	1
Raz-Pasteur, A	1
Gamliel-Lazarovich, A	1
Coleman, R	1
Keidar, S	1
Tylicki, L	2
Lizakowski, S	1
Rutkowski, P	2
Renke, M	2
Sulikowska, B	1
Heleniak, Z	1
Donderski, R	1
Bednarski, R	1
Przybylska, M	1
Manitius, J	1
Rutkowski, B	2
Suzuki, G	1
Morita, H	1
Mishima, T	1
Sharov, VG	1
Todor, A	1
Tanhehco, EJ	1
Rudolph, AE	1
McMahon, EG	1
Goldstein, S	1
Sabbah, HN	1
Ahokas, RA	1
Warrington, KJ	1
Gerling, IC	1
Sun, Y	1
Wodi, LA	1
Herring, PA	1
Lu, L	1
Bhattacharya, SK	1
Postlethwaite, AE	1
Weber, KT	1
Dzau, VJ	1
Ramirez, C	1
de Seze, J	1
Delrieu, O	1
Stojkovic, T	1
Delalande, S	1
Fourrier, F	1
Leys, D	1
Defebvre, L	1
Destée, A	1
Vermersch, P	1
Strassburg, S	1
Anker, SD	1
Epstein, M	1
Oosterhuis, JK	1
van den Berg, G	1
Monteban-Kooistra, WE	1
Ligtenberg, JJ	1
Tulleken, JE	1
Meertens, JH	1
Zijlstra, JG	1
Monrad, SU	1
Killen, PD	1
Anderson, MR	1
Bradke, A	1
Kaplan, MJ	1
Furumatsu, Y	1
Nagasawa, Y	1
Tomida, K	1
Mikami, S	1
Kaneko, T	1
Okada, N	1
Tsubakihara, Y	1
Imai, E	1
Shoji, T	1
Larczyński, W	1
Aleksandrowicz, E	1
Lysiak-Szydlowska, W	1
Kulbertus, H	1
Brown, NJ	1
Nakamura, S	1
Ma, L	1
Nakamura, I	1
Donnert, E	1
Freeman, M	1
Vaughan, DE	1
Fogo, AB	1
Stagnara, J	1
Balagny, E	1
Cossalter, B	1
Dommerges, JP	1
Dournel, C	1
Drahi, E	1
Gauchez, H	1
Guillot, F	1
Javault, D	1
Lagardère, B	1
Le Masne, A	1
Lesprit, E	1
Maidenberg, M	1
Maufroy, D	1
Picherot, G	1
Renaud, H	1
Robert, J	1
Undreiner, F	1
Spertus, JA	1
Tooley, J	1
Jones, P	1
Poston, C	1
Mahoney, E	1
Deedwania, P	1
Hurley, S	1
Weintraub, WS	1

Trial	Phase	Enrollment	Study Type	Start Date	Status
Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist (TOPCAT)[NCT00094302]	Phase 3	3,445 participants (Actual)	Interventional	2006-08-31	Completed
Proteomic Prediction and Renin Angiotensin Aldosterone System Inhibition Prevention Of Early Diabetic nephRopathy In TYpe 2 Diabetic Patients With Normoalbuminuria[NCT02040441]	Phase 2/Phase 3	1,777 participants (Actual)	Interventional	2014-03-31	Completed
A Double-Blind, Placebo-Controlled Study on the Effect of Spironolactone, in Patients With Persistent Proteinuria on Long-Term Angiotensin Converting Enzyme Inhibitor Therapy, With or With Out an Angiotensin II Receptor Blocker[NCT00106561]	Phase 2/Phase 3	60 participants	Interventional	2002-01-31	Completed
Eplerenone, ACE Inhibition and Albuminuria[NCT00315016]	Phase 2	30 participants (Actual)	Interventional	2007-01-31	Completed
Autoregulation of Glomerular Filtration Rate in Patients With Type 1 Diabetes During Spironolactone Therapy[NCT00335413]	Phase 4	17 participants (Actual)	Interventional	2006-06-30	Completed
The Effect of Aldosterone Inhibition on Proteinuria in Patients With Progressive Renal Disease[NCT00430924]	Phase 4	42 participants (Actual)	Interventional	2007-03-31	Completed
Influence of Adding Aldosterone Receptor Blocker to Dual Renin-Angiotensin-Aldosterone System Blockade on Proteinuria[NCT00528385]		0 participants	Interventional	2005-03-31	Completed
Is Spironolactone Safe and Effective in the Treatment of Cardiovascular Disease in Mild Chronic Renal Failure?[NCT00291720]	Phase 2	120 participants (Actual)	Interventional	2005-04-30	Completed
Spironolactone for Reducing Proteinuria in Diabetic Nephropathy[NCT00498537]		30 participants (Actual)	Interventional	2003-01-31	Completed
Aldosterone Blockade in Chronic Kidney Disease. Influence on Arterial Stiffness and Kidney Function[NCT01100203]	Phase 3	54 participants (Actual)	Interventional	2010-04-30	Terminated (stopped due to It was not possible within the time frame to recruit the planned no. of patients.)
A Randomized, Double-blind, Placebo-controlled, Parallel-group, Multicenter, Event-driven Phase 3 Study to Investigate the Safety and Efficacy of Finerenone, in Addition to Standard of Care, on the Progression of Kidney Disease in Subjects With Type 2 Dia[NCT02540993]	Phase 3	5,734 participants (Actual)	Interventional	2015-09-17	Completed
South Danish Hypertension and Diabetes Study[NCT01062763]	Phase 3	119 participants (Actual)	Interventional	2010-03-31	Completed
Evaluation of Safety and Efficacity of Indometacin and Two Potassium Sparing Diuretics in Adult Patients Affected by Gitelman Syndrome[NCT01146197]	Phase 1/Phase 2	33 participants (Actual)	Interventional	2010-02-28	Completed
Effect of Aldosterone Antagonism in the Reduction of Albuminuria and Diastolic Disfunction of Patients With Diabetic Nephropathy.[NCT00870402]	Phase 4	160 participants (Anticipated)	Interventional	2009-03-31	Recruiting
Improving Outcomes in Diabetic Nephropathy[NCT00381134]	Phase 2	92 participants (Anticipated)	Interventional	2003-07-31	Completed
The Effect Of Eplerenone Versus Placebo On Cardiovascular Mortality And Heart Failure Hospitalization In Subjects With NYHA Class II Chronic Systolic Heart Failure[NCT00232180]	Phase 3	2,743 participants (Actual)	Interventional	2006-03-31	Completed
A Randomized, Double-blind, Multi-center Study to Assess Safety and Tolerability of Different Oral Doses of BAY94-8862 in Subjects With Stable Chronic Heart Failure With Left Ventricular Systolic Dysfunction and Mild (Part A) or Moderate (Part B) Chronic [NCT01345656]	Phase 2	457 participants (Actual)	Interventional	2011-05-09	Completed
A Randomized, Double-blind, Placebo-controlled, Multi-center Study to Evaluate Efficacy and Safety of CS-3150 in Japanese Subjects With Type 2 Diabetes Mellitus and Microalbuminuria[NCT02345057]	Phase 2	365 participants (Actual)	Interventional	2015-01-31	Completed
Aldosterone Targeted Neurohormonal Combined With Natriuresis Therapy - HF (ATHENA-HF)[NCT02235077]	Phase 2	360 participants (Actual)	Interventional	2014-12-30	Completed
A Randomized, Double-blind, Double-dummy, Multi-center Study to Assess Safety and Efficacy of Different Oral Doses of BAY94-8862 in Subjects With Emergency Presentation at the Hospital Because of Worsening Chronic Heart Failure With Left Ventricular Systo[NCT01807221]	Phase 2	1,066 participants (Actual)	Interventional	2013-06-17	Completed
A Randomized, Double-blind, Placebo-controlled, Multi-center Study to Assess the Safety and Efficacy of Different Oral Doses of BAY94-8862 in Subjects With Type 2 Diabetes Mellitus and the Clinical Diagnosis of Diabetic Nephropathy[NCT01874431]	Phase 2	823 participants (Actual)	Interventional	2013-06-12	Completed
Comparison of Efficacy of Losartan/Spironolactone and Losartan/Enalapril on Urinary Albumin Excretion, Estimated Glomerular Filtration Rate, and Blood Pressure in Patients With Type 2 Diabetes Nephropathy[NCT01667614]	Phase 2	136 participants (Actual)	Interventional	2010-05-31	Completed
The Transition From Hypertension to Hypertensive Heart Disease and Heart Failure, the PREFERS Hypertension Study[NCT04190420]		310 participants (Anticipated)	Observational	2018-10-01	Enrolling by invitation
Effect of Spironolactone on the Progression of Coronary Calcification in Peritoneal Dialysis Patients[NCT03314493]	Phase 3	33 participants (Actual)	Interventional	2014-11-07	Completed
Renal Ageing-sarcopenia Network: a Combined Genetic, Immunological and Psychological Approach to Dissect Frailty[NCT04630132]		1,500 participants (Anticipated)	Observational	2017-03-25	Recruiting
[NCT00005757]		293 participants (Actual)	Observational	1997-09-30	Completed
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

First incidence of aborted cardiac arrest (NCT00094302)
Timeframe: Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject.

All-cause Mortality

Intervention	Events per 100 person-years (Number)
Placebo	0.09
Spironolactone	0.05

(NCT00094302)
Timeframe: Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject.

Cardiovascular Mortality

Intervention	Events per 100 person-years (Number)
Placebo	4.6
Spironolactone	4.2

(NCT00094302)
Timeframe: Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject.

Cardiovascular-related Hospitalization

Intervention	Events per 100 person-years (Number)
Placebo	3.1
Spironolactone	2.8

Hospitalization for MI, stroke or the management of heart failure, whichever occurred first (NCT00094302)
Timeframe: Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject.

Chloride

Intervention	Events per 100 person-years (Number)
Placebo	6.2
Spironolactone	5.5

Average post-baseline Chloride, taking into consideration baseline Chloride, treatment group, the time between the post-baseline measures, and the correlation between repeated measures within an individual. (NCT00094302)
Timeframe: Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject.

Composite Outcome of Cardiovascular Mortality or Cardiovascular-related Hospitalization (i.e., Hospitalization for Myocardial Infarction(MI), Stroke, or the Management of Heart Failure), Whichever Occurred First

Intervention	mEq/L (Least Squares Mean)
Placebo	102.33
Spironolactone	102.26

(NCT00094302)
Timeframe: Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject.

Composite Outcome of Cardiovascular Mortality, Aborted Cardiac Arrest, or Hospitalization for the Management of Heart Failure, Whichever Occurred First

Intervention	Events per 100 person-years (Number)
Placebo	7.8
Spironolactone	7.2

(NCT00094302)
Timeframe: Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject.

Composite Outcome of Sudden Death or Aborted Cardiac Arrest, Whichever Occurred First

Intervention	Events per 100 person-years (Number)
Placebo	6.6
Spironolactone	5.9

(NCT00094302)
Timeframe: Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject.

Composite Outcome of Sudden Death, Aborted Cardiac Arrest, or Hospitalization for the Management of Ventricular Tachycardia, Whichever Occurred First

Intervention	Events per 100 person-years (Number)
Placebo	1.1
Spironolactone	1.0

(NCT00094302)
Timeframe: Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject.

Depression Symptoms, as Measured by Patient Health Questionnaire.

Intervention	Events per 100 person-years (Number)
Placebo	1.1
Spironolactone	1.0

"Average post-baseline depression, taking into consideration baseline depression, treatment group, the time between the post-baseline measures, and the correlation between repeated measures within an individual.~The Patient Health Questionnaire (PHQ) is a 10-item, self-administered instrument for screening, diagnosing, monitoring and measuring the severity of depression. Scores can range from 0-27, in which lower scores reflect better mental health status. The PH-Q was administered at the following study visits: baseline, month 12 and annually thereafter. Valid translations of this questionnaire were only available for subjects enrolled in the United States and Canada." (NCT00094302)
Timeframe: Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject.

Deterioration of Renal Function

Intervention	units on a scale (Least Squares Mean)
Placebo	5.6
Spironolactone	5.1

First incidence of a deterioration of renal function. The TOPCAT protocol defines deterioration of renal function as occurring if a subject has a serum creatinine value which is at least double the baseline value for that subject, and is also above the upper limit of normal (assumed to be 1.0 mg/dL for females and 1.2 mg/dL for males.) (NCT00094302)
Timeframe: Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject.

Development of Atrial Fibrillation, Among Subjects Without a History of Atrial Fibrillation at Baseline.

Intervention	Events per 100 person-years (Number)
Placebo	2.2
Spironolactone	3.2

First incidence of atrial fibrillation among subjects without a history of atrial fibrillation at baseline (NCT00094302)
Timeframe: Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject.

Estimated Glomerular Filtration Rate (GFR)

Intervention	Events per 100 person-years (Number)
Placebo	1.4
Spironolactone	1.4

Average post-baseline GFR, taking into consideration baseline GFR, treatment group, the time between the post-baseline measures, and the correlation between repeated measures within an individual. (NCT00094302)
Timeframe: Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject.

Hospitalization for Any Reason

Intervention	mL/min/1.73m2 (Least Squares Mean)
Placebo	67.50
Spironolactone	65.20

First incidence of a hospitalization for any reason (NCT00094302)
Timeframe: Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject.

Hospitalization for the Management of Heart Failure

Intervention	Events per 100 person-years (Number)
Placebo	20.0
Spironolactone	18.8

First incidence of a hospitalization for the management of heart failure (NCT00094302)
Timeframe: Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject.

Myocardial Infarction

Intervention	Events per 100 person-years (Number)
Placebo	4.6
Spironolactone	3.8

First incidence of myocardial infarction (NCT00094302)
Timeframe: Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject.

New Onset Diabetes Mellitus, Among Subjects Without a History of Diabetes Mellitus at Baseline.

Intervention	Events per 100 person-years (Number)
Placebo	1.1
Spironolactone	1.2

First incidence of new onset diabetes mellitus among subjects without a history of diabetes mellitus at baseline. (NCT00094302)
Timeframe: Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject.

Potassium

Intervention	Events per 100 person-years (Number)
Placebo	0.7
Spironolactone	0.7

Average post-baseline Potassium, taking into consideration baseline Potassium, treatment group, the time between the post-baseline measures, and the correlation between repeated measures within an individual. (NCT00094302)
Timeframe: Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject.

Quality of Life, as Measured by McMaster Overall Treatment Evaluation Questionnaire.

Intervention	mEq/L (Least Squares Mean)
Placebo	4.32
Spironolactone	4.49

"Average post-baseline quality of life, taking into consideration baseline quality of life and treatment group.~The McMaster Overall Treatment Evaluation questionnaire is a self-administered 3-item instrument that measures a patient's perception of change in their health-related quality of life since the start of therapy. The questionnaire consists of a single question - Since treatment started, has there been any change in your activity limitation, symptoms and/or feelings related to your heart condition? Scores can range from -7 to +7, and higher scores reflect better health status. The questionnaire was administered at the following study visits: month 4 and month 12. Valid translations of this questionnaire were only available for subjects enrolled in the United States, Canada and Argentina." (NCT00094302)
Timeframe: Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject.

Quality of Life, as Measured by the EuroQOL Visual Analog Scale.

Intervention	units on a scale (Least Squares Mean)
Placebo	1.2
Spironolactone	1.2

"Average post-baseline quality of life, taking into consideration baseline quality of life, treatment group, the time between the post-baseline measures, and the correlation between repeated measures within an individual.~The EuroQOL visual analog scale (EQ5D) is a single-item, self-administered instrument that quantifies current health status. Scores can range from 0-100, in which higher scores reflect better health status. The EQ5D was administered at the following study visits: baseline, month 4, month 12 and annually thereafter." (NCT00094302)
Timeframe: Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject.

Quality of Life, as Measured by the Kansas City Cardiomyopathy Questionnaire.

Intervention	units on a scale (Least Squares Mean)
Placebo	65.9
Spironolactone	66.4

"Average post-baseline quality of life, taking into consideration baseline quality of life, treatment group, the time between the post-baseline measures, and the correlation between repeated measures within an individual.~The Kansas City Cardiomyopathy Questionnaire (KCCQ) is a 23-item, self-administered instrument that quantifies physical function, symptoms (frequency, severity and recent change), social function, self-efficacy and knowledge, and quality of life. Scores are transformed to a range of 0-100, in which higher scores reflect better health status. The KCCQ was administered at the following study visits: baseline, month 4, month 12 and annually thereafter." (NCT00094302)
Timeframe: Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject.

Serum Creatinine

Intervention	units on a scale (Least Squares Mean)
Placebo	63.1
Spironolactone	64.4

Average post-baseline serum creatinine, taking into consideration baseline serum creatinine, treatment group, the time between the post-baseline measures, and the correlation between repeated measures within an individual. (NCT00094302)
Timeframe: Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject.

Sodium

Intervention	mg/dL (Least Squares Mean)
Placebo	1.11
Spironolactone	1.17

Average post-baseline Sodium, taking into consideration baseline Sodium, treatment group, the time between the post-baseline measures, and the correlation between repeated measures within an individual. (NCT00094302)
Timeframe: Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject.

Stroke

Intervention	mEq/L (Least Squares Mean)
Placebo	140.95
Spironolactone	140.33

First incidence of stroke (NCT00094302)
Timeframe: Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject.

Total Hospitalizations (Including Repeat Hospitalizations) for the Management of Heart Failure

Intervention	Events per 100 person-years (Number)
Placebo	1.1
Spironolactone	1.0

(NCT00094302)
Timeframe: Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject.

All-cause Hospitalization

Intervention	Events per 100 person-years (Number)
Placebo	8.3
Spironolactone	6.8

Count of participants and time from randomization to the first occurrence of a hospitalization event were evaluated. Number of participants with the event is reported as descriptive result and hazard ratio is reported as statistical analysis. (NCT02540993)
Timeframe: From randomization up until the first occurrence of the hospitalization due to any cause, or censoring at the end of study, with an average of 32 months

All-cause Mortality

Intervention	Participants (Count of Participants)
Finerenone	1263
Placebo	1321

Count of participants and time from randomization until death due to any cause were evaluated. Number of participants with outcome death is reported as descriptive result and hazard ratio is reported as statistical analysis. Number of participants with outcome death reported here includes deaths occurred after randomization until the end of the study visit. Deaths after end of study visit are not included in this table. (NCT02540993)
Timeframe: From randomization up until death due to any cause, or censoring at the end of the study visit, with an average of 32 months

Change in Urinary Albumin-to-creatinine Ratio (UACR) From Baseline to Month 4

Intervention	Participants (Count of Participants)
Finerenone	219
Placebo	244

First morning void urine samples were collected to evaluate the urinary albumin-to-creatinine ratio (UACR). Month 4 was the visit closest to day 120 within a time window of 120 ± 30 days after randomization. If no measurements were available in this time window, the participant was excluded from this analysis. Ratio of UACR at Month 4 to UACR at baseline is reported as the change. (NCT02540993)
Timeframe: From baseline up until Month 4

The First Occurrence of the Composite Endpoint of Cardiovascular Death, Non-fatal Myocardial Infarction, Non-fatal Stroke, or Hospitalization for Heart Failure

Intervention	Ratio (Least Squares Mean)
Finerenone	0.655
Placebo	0.952

Count of participants and time from randomization to the first occurrence of the key secondary cardiovascular (CV) composite outcome, CV death, non-fatal myocardial infarction (MI), non-fatal stroke, or hospitalization for heart failure were evaluated. Number of participants with the outcome event is reported as descriptive result and hazard ratio is reported as statistical analysis. (NCT02540993)
Timeframe: From randomization up until the first occurrence of the key secondary CV composite endpoint, or censoring at the end of the study, with an average of 32 months

The First Occurrence of the Composite Endpoint of Onset of Kidney Failure, a Sustained Decrease in eGFR of ≥57% From Baseline Over at Least 4 Weeks, or Renal Death

Intervention	Participants (Count of Participants)
Finerenone	367
Placebo	420

Count of participants and time from randomization to the first occurrence of the secondary renal composite outcome, onset of kidney failure, a sustained decrease in eGFR of ≥57% from baseline over at least 4 weeks, or renal death were evaluated. Number of participants with the outcome event is reported as descriptive result and hazard ratio is reported as statistical analysis. (NCT02540993)
Timeframe: From randomization up until the first occurrence of the composite primary endpoint, or censoring at the end of the study, with an average of 32 months

The First Occurrence of the Composite Endpoint of Onset of Kidney Failure, a Sustained Decrease of eGFR ≥40% From Baseline Over at Least 4 Weeks, or Renal Death

Intervention	Participants (Count of Participants)
Finerenone	252
Placebo	326

Count of participants and time from randomization to the first occurrence of the primary renal composite outcome, onset of kidney failure, a sustained decrease of eGFR ≥40% from baseline over at least 4 weeks, or renal death were evaluated. Number of participants with the outcome event is reported as descriptive result and hazard ratio is reported as statistical analysis. (NCT02540993)
Timeframe: From randomization up until the first occurrence of the primary renal composite endpoint, or censoring at the end of the study, with an average follow-up time of 32 months

Adverse Effects

Change of Diastolic Blood Pressure

Intervention	Participants (Count of Participants)
Finerenone	504
Placebo	600

Intervention	participants (Number)
Addition of Spironolactone	4
Placebo	0

Change of diastolic blood pressure from baseline to study end at four months. (NCT01062763)
Timeframe: 4 months

Change of of Systolic Blood Pressure

Intervention	mm Hg (Mean)
Addition of Spironolactone	-3.9
Placebo	-0.3

Change of systolic blood pressure from baseline to study end at four months. (NCT01062763)
Timeframe: 4 months

Number of Participants With First Occurrence of Cardiovascular (CV) Mortality or Hospitalization Due to Heart Failure (HF) (Adjudicated)

Intervention	mm Hg (Mean)
Addition of Spironolactone	-9.6
Placebo	-0.7

CV mortality is defined as death due to heart failure, myocardial infarction, cardiac arrhythmia, stroke or cerebral vascular accident (CVA), other CV cause (such as aneurysm or pulmonary embolism). Hospitalization due to HF is defined as an overnight stay, or longer, in a hospital environment (emergency room, observation unit or in-patient care, or similar facility including admission to a day care facility) due to HF as the primary reason for hospitalization as determined by the endpoint committee adjudicator. (NCT00232180)
Timeframe: Baseline (30 March 2006) up to 59.5 months (complete DB phase: 18 March 2011)

Number of Participants With First Occurrence of Cardiovascular (CV) Mortality or Hospitalization Due to Heart Failure (HF) (Adjudicated): Up to Cut-off Date

Intervention	participants (Number)
Eplerenone: Double-blind Phase	288
Placebo: Double-blind Phase	392

Number of Participants With First Occurrence of All-Cause Hospitalization (Adjudicated)

Intervention	participants (Number)
Eplerenone: Double-blind Phase	249
Placebo: Double-blind Phase	356

Hospitalization due to any cause is defined as an overnight stay, or longer, in a hospital environment (emergency room, observation unit or in-patient care, or similar facility including admission to a day care facility). (NCT00232180)
Timeframe: Baseline (30 March 2006) up to 50 months (cut-off date: 25 May 2010), 59.5 months (complete DB phase: 18 March 2011)

Number of Participants With First Occurrence of All-Cause Mortality (Adjudicated)

Intervention	participants (Number)
	Up to 50 months (cut-off) (n= 1364, 1373)	Up to 59.5 months (complete DB) (n= 1367, 1376)
Eplerenone: Double-blind Phase	408	463
Placebo: Double-blind Phase	491	552

Death due to any cause. (NCT00232180)
Timeframe: Baseline (30 March 2006) up to 50 months (cut-off date: 25 May 2010), 59.5 months (complete DB phase: 18 March 2011)

Number of Participants With First Occurrence of All-Cause Mortality or All-Cause Hospitalization (Adjudicated)

Intervention	participants (Number)
	Up to 50 months (cut-off) (n= 1364, 1373)	Up to 59.5 months (complete DB) (n= 1367, 1376)
Eplerenone: Double-blind Phase	171	205
Placebo: Double-blind Phase	213	253

Death due to any cause or hospitalization due to any cause. Hospitalization due to any cause is defined as an overnight stay, or longer, in a hospital environment (emergency room, observation unit or in-patient care, or similar facility including admission to a day care facility). (NCT00232180)
Timeframe: Baseline (30 March 2006) up to 50 months (cut-off date: 25 May 2010), 59.5 months (complete DB phase: 18 March 2011)

Number of Participants With First Occurrence of All-Cause Mortality or Heart Failure (HF) Hospitalization (Adjudicated)

Intervention	participants (Number)
	Up to 50 months (cut-off) (n= 1364, 1373)	Up to 59.5 months (complete DB) (n= 1367, 1376)
Eplerenone: Double-blind Phase	462	530
Placebo: Double-blind Phase	569	636

Death due to any cause or first of occurrence HF hospitalization. HF hospitalization is defined as an overnight stay, or longer, in a hospital environment (emergency room, observation unit or in-patient care, or similar facility including admission to a day care facility) due to HF as the primary reason for hospitalization as determined by the endpoint committee adjudicator. (NCT00232180)
Timeframe: Baseline (30 March 2006) up to 50 months (cut-off date: 25 May 2010), 59.5 months (complete DB phase: 18 March 2011)

Number of Participants With First Occurrence of Cardiovascular (CV) Hospitalization (Adjudicated)

Intervention	participants (Number)
	Up to 50 months (cut-off) (n= 1364, 1373)	Up to 59.5 months (complete DB) (n= 1367, 1376)
Eplerenone: Double-blind Phase	270	311
Placebo: Double-blind Phase	376	418

First occurrence of CV hospitalization. CV hospitalization is defined as hospitalization due to HF (first or subsequent), acute myocardial infarction, angina pectoris (unstable), cardiac arrhythmia (atrial fibrillation [AF], atrial flutter, supraventricular arrhythmias, or ventricular arrhythmias), stroke/CVA, other CV reasons (such as hypotension or peripheral vascular disease), implantation of a cardioverter defibrillator (ICD), or cardiac resynchronization therapy (CRT) with CV event as the primary reason for hospitalization as determined by endpoint committee adjudicator. (NCT00232180)
Timeframe: Baseline (30 March 2006) up to 50 months (cut-off date: 25 May 2010), 59.5 months (complete DB phase: 18 March 2011)

Number of Participants With First Occurrence of Cardiovascular (CV) Mortality (Adjudicated)

Intervention	participants (Number)
	Up to 50 months (cut-off) (n= 1364, 1373)	Up to 59.5 months (complete DB) (n= 1367, 1376)
Eplerenone: Double-blind Phase	304	346
Placebo: Double-blind Phase	399	439

CV mortality is defined as death due to heart failure, myocardial infarction, cardiac arrhythmia, stroke or cerebral vascular accident (CVA), other CV cause (such as aneurysm or pulmonary embolism). (NCT00232180)
Timeframe: Baseline (30 March 2006) up to 50 months (cut-off date: 25 May 2010), 59.5 months (complete DB phase: 18 March 2011)

Number of Participants With First Occurrence of Fatal or Non-fatal Myocardial Infarction (Adjudicated)

Intervention	participants (Number)
	Up to 50 months (cut-off) (n= 1364, 1373)	Up to 59.5 months (complete DB) (n= 1367, 1376)
Eplerenone: Double-blind Phase	147	178
Placebo: Double-blind Phase	185	215

(NCT00232180)
Timeframe: Baseline (30 March 2006) up to 50 months (cut-off date: 25 May 2010), 59.5 months (complete DB phase: 18 March 2011)

Number of Participants With First Occurrence of Fatal or Non-fatal Stroke (Adjudicated)

Intervention	participants (Number)
	Up to 50 months (cut-off) (n= 1364, 1373)	Up to 59.5 months (complete DB) (n= 1367, 1376)
Eplerenone: Double-blind Phase	45	49
Placebo: Double-blind Phase	33	40

(NCT00232180)
Timeframe: Baseline (30 March 2006) up to 50 months (cut-off date: 25 May 2010), 59.5 months (complete DB phase: 18 March 2011)

Number of Participants With First Occurrence of Heart Failure (HF) Hospitalization (Adjudicated)

Intervention	participants (Number)
	Up to 50 months (cut-off) (n= 1364, 1373)	Up to 59.5 months (complete DB) (n= 1367, 1376)
Eplerenone: Double-blind Phase	21	24
Placebo: Double-blind Phase	26	31

First occurrence of HF hospitalization. Hospitalization due to HF is defined as an overnight stay, or longer, in a hospital environment (emergency room, observation unit or in-patient care, or similar facility including admission to a day care facility) due to HF as the primary reason for hospitalization as determined by the endpoint committee adjudicator. (NCT00232180)
Timeframe: Baseline (30 March 2006) up to 50 months (cut-off date: 25 May 2010), 59.5 months (complete DB phase: 18 March 2011)

Number of Participants With First Occurrence Of Heart Failure (HF) Mortality or Heart Failure (HF) Hospitalization (Adjudicated)

Intervention	participants (Number)
	Up to 50 months (cut-off) (n= 1364, 1373)	Up to 59.5 months (complete DB) (n= 1367, 1376)
Eplerenone: Double-blind Phase	164	186
Placebo: Double-blind Phase	253	277

Death due to HF or first occurrence of HF hospitalization. Hospitalization due to HF is defined as an overnight stay, or longer, in a hospital environment (emergency room, observation unit or in-patient care, or similar facility including admission to a day care facility) due to HF as the primary reason for hospitalization as determined by the endpoint committee adjudicator. (NCT00232180)
Timeframe: Baseline (30 March 2006) up to 50 months (cut-off date: 25 May 2010), 59.5 months (complete DB phase: 18 March 2011)

Number of Participants With First Occurrence of Hospitalization Due to Hyperkalemia (Adjudicated)

Intervention	participants (Number)
	Up to 50 months (cut-off) (n= 1364, 1373)	Up to 59.5 months (complete DB) (n= 1367, 1376)
Eplerenone: Double-blind Phase	170	194
Placebo: Double-blind Phase	262	287

First occurrence of hospitalization due to hyperkalemia. Hospitalization due to hyperkalemia is defined as an overnight stay, or longer, in a hospital environment (emergency room, observation unit or in-patient care, or similar facility including admission to a day care facility) due to hyperkalemia as the primary reason for hospitalization as determined by endpoint committee adjudicator. Hyperkalemia is defined as serum potassium level greater than (>) 5.5 milliequivalents per liter (mEq/L). (NCT00232180)
Timeframe: Baseline (30 March 2006) up to 50 months (cut-off date: 25 May 2010), 59.5 months (complete DB phase: 18 March 2011)

Number of Participants With First Occurrence of Hospitalization Due to Worsening Renal Function (Adjudicated)

First occurrence of hospitalization due to worsening renal function. Hospitalization due to worsening renal function is defined as an overnight stay, or longer, in a hospital environment (emergency room, observation unit or in-patient care, or similar facility including admission to a day care facility) due to worsening renal function as the primary reason for hospitalization as determined by endpoint committee adjudicator. Worsening renal function is defined as doubling of serum creatinine level from baseline level. (NCT00232180)
Timeframe: Baseline (30 March 2006) up to 50 months (cut-off date: 25 May 2010), 59.5 months (complete DB phase: 18 March 2011)

Number of Participants With First Occurrence of Implantation of Cardiac Defibrillator (ICD) (Adjudicated)

First occurrence of implantation of cardiac defibrillator (ICD). ICD is an electronic device capable of monitoring the heart rhythm. When the heart is beating normally, the device remains inactive. If the heart develops a life-threatening tachycardia, the ICD delivers electrical shocks to the heart to terminate the abnormal rhythm and return the heart rhythm to normal. (NCT00232180)
Timeframe: Baseline (30 March 2006) up to 50 months (cut-off date: 25 May 2010), 59.5 months (complete DB phase: 18 March 2011)

Number of Participants With First Occurrence of Implantation of Resynchronization Device (Cardiac Resynchronization Therapy [CRT]) (Adjudicated)

First occurrence of implantation of resynchronization device. CRT is use of a specialized pacemaker to re-coordinate the action of the right and left ventricles in heart failure. (NCT00232180)
Timeframe: Baseline (30 March 2006) up to 50 months (cut-off date: 25 May 2010), 59.5 months (complete DB phase: 18 March 2011)

Number of Participants With New Onset Atrial Fibrillation or Flutter

New onset of atrial fibrillation or flutter is defined as the diagnosis of atrial fibrillation or flutter in a participant after randomization, where atrial fibrillation was not present before randomization. (NCT00232180)
Timeframe: Baseline (30 March 2006) up to 50 months (cut-off date: 25 May 2010), 59.5 months (complete DB phase: 18 March 2011)

Number of Participants With New Onset Diabetes Mellitus (DM)

The definition of new onset diabetes mellitus is the diagnosis of diabetes mellitus in a participant after randomization, when DM was not present before randomization. (NCT00232180)
Timeframe: Baseline (30 March 2006) up to 50 months (cut-off date: 25 May 2010), 59.5 months (complete DB phase: 18 March 2011)

96 Hour Change in Body Weight

Baseline body weight assessment will be completed, and changes in weight documented daily through 96 hours or earlier discharge (NCT02235077)
Timeframe: Randomization through 96 hours or earlier discharge

96 Hour Change in Clinical Congestion Score

Clinical congestion score will be assessed at randomization, 96 hours, and at discharge. Scale consisted of sum of six signs and symptoms of congestion, each scored 0-3. Zero indicates no sign/symptom and 3 indicates worst case of sign/symptom. Score range 0-18 with 18 being worst score. (NCT02235077)
Timeframe: Randomization through 96 hours

96 Hour Change in Dyspnea Visual Analog Scale

Dyspnea visual analog scale change from randomization to 96 hours. Scale range 0-100 with 100 being the best possible score. (NCT02235077)
Timeframe: Randomization to 96 hours

96 Hour Change in NT-proBNP

The Core Laboratory at Vermont will determine NT-proBNP levels for calculation of the endpoint from samples obtained at randomization and 96 hours respectively. NT-proBNP was converted to log scale. (NCT02235077)
Timeframe: Randomization to 96 hours

96 Hour Change in Serum Creatinine

Renal function via serum creatinine, will be assessed at randomization and daily through 96 hours (NCT02235077)
Timeframe: Randomization through 96 hours

96 Hour Change in Serum Potassium Levels

Change in serum potassium levels at 96 hours as compared to baseline. (NCT02235077)
Timeframe: Baseline, 96 hours

96 Hour Net Fluid Output

Fluid intake and urine output will be assessed daily while in hospital through 96 hours. Net fluid output (output minus input) through 96 hours is reported. (NCT02235077)
Timeframe: Randomization through 96 hours

Change in Loop Diuretics Requirements From Baseline to 30 Days

Medications will be reviewed to assess loop diuretic dose requirements through Day 30 following randomization (NCT02235077)
Timeframe: Randomization through Day 30

Day 60 Mortality

All participants will be contacted by telephone at 60 days, +/- 3 days post randomization to assess vital status (death). (NCT02235077)
Timeframe: 60 days post randomization

Presence of Outpatient Worsening Heart Failure Symptoms Through Day 30

Outpatient worsening heart failure symptoms will be assessed from discharge through Day 30 (NCT02235077)
Timeframe: Hospital discharge through Day 30

Percentage of Participants With a Relative Decrease in NT-proBNP of More Than 30% From Baseline to Day 90

N-terminal pro-B type natriuretic peptide (NT-proBNP) levels in the blood are used for screening, diagnosis of acute and chronic heart failure (CHF) and may be useful to establish prognosis in heart failure. (NCT01807221)
Timeframe: Baseline and Day 90

Change From Baseline in Diastolic Blood Pressure at Specified Visits

(NCT01807221)
Timeframe: Baseline,Day 7,14,30,60,90,Premature discontinuation (only for participants who have discontinued the study prematurely, to be performed as soon as possible after withdrawal of study drug) and Follow-up (30 days post-last dose, assessed up to Day 120)

Change From Baseline in EQ-5D-3L Questionnaire Scores at Specified Visits

EuroQol Group 5-Dimension, 3-Level (EQ-5D-3L): participant rated questionnaire to assess health-related quality of life. It consists of EQ-5D descriptive system and EQ-5D Visual Analog Scale (VAS). EQ-5D-3L descriptive system comprises the following 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 3 levels: no problems (1), some problems (2), and extreme problems (3). For this population, the possible EQ-5D-3L index scores ranges from -0.11 (that is, 3 for all 5 dimensions) to 1.0 (that is, 1 for all 5 dimensions), where higher scores indicate a better health state. (NCT01807221)
Timeframe: Baseline, Day 30, Day 90, Premature discontinuation (only for participants who have discontinued the study prematurely, to be performed as soon as possible after withdrawal of study drug) and Follow-up (30 days post-last dose, assessed up to Day 120)

Change From Baseline in Heart Rate at Specified Visits

Change From Baseline in KCCQ Questionnaire Scores at Specified Visits

The Kansas City Cardiomyopathy Questionnaire (KCCQ) was the leading health related quality of life measure for subjects with CHF. KCCQ was a 23 item questionnaire that independently measures the impact of subjects HF, or its treatment, on 7 distinct domains: self-administered instrument that quantifies physical function, symptoms (frequency, severity and recent change), social function, self-efficacy and knowledge, and quality of life. KCCQ clinical summary score is a composite assessment of physical limitations and total symptom scores. Results from the total symptom summary score are presented. Scores are transformed to a range of 0-100, in which higher scores reflect better health status. In the below table, categorical data represents change from baseline data at respective time points. (NCT01807221)
Timeframe: Baseline, Day 30 and Day 90

Change From Baseline in Serum Potassium at Specified Visits

(NCT01807221)
Timeframe: Baseline, Day 30, Day 60, Day 90 and Follow-up (30 days post-last dose, assessed up to Day 120)

Change From Baseline in Systolic Blood Pressure at Specified Visits

Number of Participants With Cardiovascular Hospitalization

Hospitalizations were defined as any unplanned admission to hospital, i.e. completion of hospital admission procedures and one overnight [i.e. date change] stay or until the death of subject occurred. Hospitalizations and deaths were classified by 2 primary categories: CV and non-CV. The pre-specified subcategories for CV hospitalizations were as follows: 1. Worsening heart failure, 2.Acute myocardial infarction, 3. Arrhythmia, 4.Transient ischemic attack and stroke, 5. Other CV hospitalizations. (NCT01807221)
Timeframe: Day 30, Day 60, Day 90 and Follow-up (30 days post-last dose, assessed up to Day 120)

Number of Participants With Death Due to Any Cause

Death due to any cause include cardiovascular (CV) death and Non-CV death. Non-CV death was classified by 2 subcategories: non-malignant causes and malignant causes. (NCT01807221)
Timeframe: Day 30, Day 60, Day 90 and Follow-up (30 days post-last dose, assessed up to Day 120)

Number of Participants With Emergency Presentations for Worsening Chronic Heart Failure (WCHF)

Emergency presentations for WCHF were defined as newly developing signs and symptoms of WCHF after start of treatment with study drug, requiring an additional emergency presentation to hospital and IV treatment with diuretics and/or positive inotropic agents. (NCT01807221)
Timeframe: Day 30, Day 60, Day 90 and Follow-up (30 days post-last dose, assessed up to Day 120)

Ratio of BNP at Specified Visits to BNP at Baseline

B-type natriuretic peptide (BNP) levels in the blood are used for screening, diagnosis of acute chronic heart failure (CHF) and may be useful to establish prognosis in heart failure. (NCT01807221)
Timeframe: Day 30, Day 60, Day 90, Premature discontinuation (only for participants who have discontinued the study prematurely, to be performed as soon as possible after withdrawal of study drug) and Follow-up (30 days post-last dose, assessed up to Day 120)

Ratio of NT-proBNP at Specified Visits to NT-proBNP at Baseline

N-terminal pro-B type natriuretic peptide (NT-proBNP) levels in the blood are used for screening, diagnosis of acute chronic heart failure (CHF) and may be useful to establish prognosis in heart failure. (NCT01807221)
Timeframe: Day 30, Day 60, Day 90, Premature discontinuation (only for participants who have discontinued the study prematurely, to be performed as soon as possible after withdrawal of study drug) and Follow-up (30 days post-last dose, assessed up to Day 120)

Change From Baseline to Day 90 in eGFR

An estimated glomerular filtration rate (eGFR) indicates the renal function. An eGFR was calculated based on the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula. (NCT01874431)
Timeframe: Baseline and Day 90±2

Change From Baseline to Day 90 in EQ-5D Scores (EQ5D - Visual Analog Scale)

EuroQol Group 5-Dimension, 3-Level (EQ-5D-3L) questionnaires consist of the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS). The EQ-5D-3L descriptive system comprises the following 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 3 levels: no problems, some problems, extreme problems. EQ VAS was analyzed for this endpoint and it ranges from 0 (worst possible health state) to 100 (best possible health state). (NCT01874431)
Timeframe: Baseline and Day 90±2

Change From Baseline to Day 90 in KDQOL-36 Domain Score (Effects of Kidney Disease)

"The Kidney Disease QOL [KDQOL]-36 questionnaire is a specific measure of Health-Related Quality of Life (HRQoL) for chronic kidney disease (CKD) that includes effects and burden of kidney disease as well as physical and mental health scores. Index score ranges from 0 (severe problems in all items) to 100 (no problem in all items). Effects of Kidney disease subscore was analyzed." (NCT01874431)
Timeframe: Baseline and Day 90±2

Change From Baseline to Day 90 in Serum Potassium

Ratio of UACR at Day 90 to UACR at Baseline

Albumin-to-creatinine ratio (UACR) is defined as gram of albumin per kilogram of creatinine. UACR was calculating the average of 3 first morning void samples taken on 3 consecutive days. (NCT01874431)
Timeframe: Baseline and Day 90±2

Intervention	participants (Number)
	Up to 50 months (cut-off) (n= 950, 937)	Up to 59.5 months (complete DB) (n= 956, 940)
Eplerenone: Double-blind Phase	32	41
Placebo: Double-blind Phase	52	59

Intervention	participants (Number)
	Up to 50 months (cut-off) (n= 904, 973)	Up to 59.5 months (complete DB) (n= 907, 975)
Eplerenone: Double-blind Phase	34	42
Placebo: Double-blind Phase	40	47

Intervention	Percentage of participants (Number)
Eplerenone (INSPRA®)	37.2
Finerenone (BAY94-8862) 2.5-5 mg OD	30.9
Finerenone (BAY94-8862) 5-10 mg OD	32.5
Finerenone (BAY94-8862) 7.5-15 mg OD	37.3
Finerenone (BAY94-8862) 10-20 mg OD	38.8
Finerenone (BAY94-8862) 15-20 mg OD	34.2

Intervention	millimeter for mercury (mmHg) (Mean)
	Baseline	Day 7	Day 14	Day 30	Day 60	Day 90	Premature discontinuation	Follow-up
Eplerenone (INSPRA®)	71.633	-1.351	-3.442	-0.503	-0.613	-0.716	-3.185	-1.218
Finerenone (BAY94-8862) 10-20 mg OD	70.343	-0.738	-2.387	-0.094	0.17	-0.545	-2.96	-0.298
Finerenone (BAY94-8862) 15-20 mg OD	71.145	-1.166	-0.625	-1.163	-0.575	-0.877	-0.083	-0.172
Finerenone (BAY94-8862) 2.5-5 mg OD	71.044	-1.693	-0.537	0.146	-0.199	-0.106	0.868	0.696
Finerenone (BAY94-8862) 5-10 mg OD	71.442	-2.143	1.608	-0.845	-2.144	-1.738	-2.194	-0.444
Finerenone (BAY94-8862) 7.5-15 mg OD	70.61	0.013	-0.083	-0.068	-0.85	-1.121	4.101	-1.16

Intervention	mL/min/1.73m^2 (Least Squares Mean)
Finerenone (BAY94-8862) (1.25 mg)	-2.364
Finerenone (BAY94-8862) (2.5 mg)	-3.189
Finerenone (BAY94-8862) (5 mg)	-2.497
Finerenone (BAY94-8862) (7.5 mg)	-3.378
Finerenone (BAY94-8862) (10 mg)	-4.192
Finerenone (BAY94-8862) (15 mg)	-3.806
Finerenone (BAY94-8862) (20 mg)	-4.024
Placebo	-1.578

Intervention	scores on a scale (Least Squares Mean)
Finerenone (BAY94-8862) (1.25 mg)	1.381
Finerenone (BAY94-8862) (2.5 mg)	3.888
Finerenone (BAY94-8862) (5 mg)	3.124
Finerenone (BAY94-8862) (7.5 mg)	2.851
Finerenone (BAY94-8862) (10 mg)	2.698
Finerenone (BAY94-8862) (15 mg)	2.743
Finerenone (BAY94-8862) (20 mg)	1.914
Placebo	4.425

Intervention	scores on a scale (Least Squares Mean)
Finerenone (BAY94-8862) (1.25 mg)	-2.116
Finerenone (BAY94-8862) (2.5 mg)	0.104
Finerenone (BAY94-8862) (5 mg)	-1.229
Finerenone (BAY94-8862) (7.5 mg)	-1.185
Finerenone (BAY94-8862) (10 mg)	-2.596
Finerenone (BAY94-8862) (15 mg)	0.112
Finerenone (BAY94-8862) (20 mg)	0.058
Placebo	0.747

Intervention	millimole per liter (Least Squares Mean)
Finerenone (BAY94-8862) (1.25 mg)	0.109
Finerenone (BAY94-8862) (2.5 mg)	0.123
Finerenone (BAY94-8862) (5 mg)	0.202
Finerenone (BAY94-8862) (7.5 mg)	0.127
Finerenone (BAY94-8862) (10 mg)	0.167
Finerenone (BAY94-8862) (15 mg)	0.238
Finerenone (BAY94-8862) (20 mg)	0.188
Placebo	0.002

Intervention	Ratio (Least Squares Mean)
Finerenone (BAY94-8862) (1.25 mg)	0.869
Finerenone (BAY94-8862) (2.5 mg)	0.89
Finerenone (BAY94-8862) (5 mg)	0.824
Finerenone (BAY94-8862) (7.5 mg)	0.739
Finerenone (BAY94-8862) (10 mg)	0.708
Finerenone (BAY94-8862) (15 mg)	0.63
Finerenone (BAY94-8862) (20 mg)	0.585
Placebo	0.938

Article	Year
Effect of spironolactone on the progression of coronary calcification in peritoneal dialysis patients: a pilot study. Jornal brasileiro de nefrologia, 2019, Aug-15, Volume: 41, Issue:3 Topics: Aged; Calcium; Cholesterol, LDL; Disease Progression; Female; Follow-Up Studies; Humans; Lost to Fol	2019
Role of Ischemic Heart Disease in Major Adverse Renal and Cardiac Events Among Individuals With Heart Failure With Preserved Ejection Fraction (from the TOPCAT Trial). The American journal of cardiology, 2021, 03-01, Volume: 142 Topics: Aged; Cardiovascular Diseases; Case-Control Studies; Creatinine; Diabetes Mellitus; Disease Progress	2021
Treatment of Unruptured Cerebral Aneurysms with the Mineralocorticoid Receptor Blocker Eplerenone-Pilot Study. Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association, 2018, Volume: 27, Issue:8 Topics: Aged; Aneurysm, Ruptured; Brain; Disease Progression; Eplerenone; Female; Follow-Up Studies; Humans;	2018
Biomarker-based phenotyping of myocardial fibrosis identifies patients with heart failure with preserved ejection fraction resistant to the beneficial effects of spironolactone: results from the Aldo-DHF trial. European journal of heart failure, 2018, Volume: 20, Issue:9 Topics: Aged; Biomarkers; Cardiomyopathies; Disease Progression; Dose-Response Relationship, Drug; Double-Bl	2018
Mineralocorticoid receptor antagonism in acutely decompensated chronic heart failure. European journal of internal medicine, 2014, Volume: 25, Issue:1 Topics: Acute Disease; Aged; Aged, 80 and over; Chronic Disease; Disease Progression; Diuretics; Edema; Fema	2014
Benefits of Aldosterone Receptor Antagonism in Chronic Kidney Disease (BARACK D) trial-a multi-centre, prospective, randomised, open, blinded end-point, 36-month study of 2,616 patients within primary care with stage 3b chronic kidney disease to compare t Trials, 2014, May-08, Volume: 15 Topics: Cardiovascular Diseases; Clinical Protocols; Disease Progression; Drug Administration Schedule; Fema	2014
Rationale and Design of the ATHENA-HF Trial: Aldosterone Targeted Neurohormonal Combined With Natriuresis Therapy in Heart Failure. JACC. Heart failure, 2016, Volume: 4, Issue:9 Topics: Acute Disease; Cause of Death; Disease Progression; Double-Blind Method; Dyspnea; Heart Failure; Hum	2016
Antifibrotic effects of aldosterone receptor blocker (spironolactone) in patients with chronic kidney disease. Renal failure, 2009, Volume: 31, Issue:9 Topics: Adrenergic Antagonists; Adult; Angiotensin-Converting Enzyme Inhibitors; Disease Progression; Female	2009
Intensive versus conventional therapy to slow the progression of idiopathic glomerular diseases. American journal of kidney diseases : the official journal of the National Kidney Foundation, 2010, Volume: 55, Issue:4 Topics: Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Disease Progression; Dru	2010
A randomized, double-blind, placebo-controlled trial of spironolactone on carotid intima-media thickness in nondiabetic hemodialysis patients. Clinical journal of the American Society of Nephrology : CJASN, 2010, Volume: 5, Issue:8 Topics: Aged; Biomarkers; Carotid Arteries; Carotid Artery Diseases; Chile; Disease Progression; Double-Blin	2010
Rationale and design of the 'aldosterone receptor blockade in diastolic heart failure' trial: a double-blind, randomized, placebo-controlled, parallel group study to determine the effects of spironolactone on exercise capacity and diastolic function in pa European journal of heart failure, 2010, Volume: 12, Issue:8 Topics: Aldosterone; Diastole; Disease Progression; Diuretics; Double-Blind Method; Exercise Tolerance; Heal	2010
Spironolactone use at discharge was associated with improved survival in hospitalized patients with systolic heart failure. American heart journal, 2010, Volume: 160, Issue:6 Topics: Aged; Disease Progression; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Heart Failur	2010
Eplerenone and atrial fibrillation in mild systolic heart failure: results from the EMPHASIS-HF (Eplerenone in Mild Patients Hospitalization And SurvIval Study in Heart Failure) study. Journal of the American College of Cardiology, 2012, May-01, Volume: 59, Issue:18 Topics: Aged; Atrial Fibrillation; Disease Progression; Dose-Response Relationship, Drug; Electrocardiograph	2012
The enhanced renin-angiotensin-aldosteron system pharmacological blockade--which is the best?. Kidney & blood pressure research, 2012, Volume: 36, Issue:1 Topics: Adult; Albuminuria; Amides; Angiotensin Receptor Antagonists; Benzimidazoles; Benzoates; Comorbidity	2012
Antagonists of aldosterone and proteinuria in patients with CKD: an uncontrolled pilot study. American journal of kidney diseases : the official journal of the National Kidney Foundation, 2005, Volume: 46, Issue:1 Topics: Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive	2005
Effect of renin-angiotensin-aldosterone system triple blockade on non-diabetic renal disease: addition of an aldosterone blocker, spironolactone, to combination treatment with an angiotensin-converting enzyme inhibitor and angiotensin II receptor blocker. Hypertension research : official journal of the Japanese Society of Hypertension, 2008, Volume: 31, Issue:1 Topics: Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; C	2008
Triple pharmacological blockade of the renin-angiotensin-aldosterone system in nondiabetic CKD: an open-label crossover randomized controlled trial. American journal of kidney diseases : the official journal of the National Kidney Foundation, 2008, Volume: 52, Issue:3 Topics: Acetylglucosaminidase; Adult; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme	2008
[Study of the month. The RALES study (randomized aldactone evaluation study]. Revue medicale de Liege, 1999, Volume: 54, Issue:9 Topics: Death, Sudden, Cardiac; Disease Progression; Double-Blind Method; Female; Heart Failure; Humans; Mal	1999
Expanding the outcomes in clinical trials of heart failure: the quality of life and economic components of EPHESUS (EPlerenone's neuroHormonal Efficacy and SUrvival Study). American heart journal, 2002, Volume: 143, Issue:4 Topics: Antihypertensive Agents; Cost-Benefit Analysis; Disease Progression; Eplerenone; Health Status Indic	2002

Article	Year
The effect of spironolactone on cardiac and renal fibrosis following myocardial infarction in established hypertension in the transgenic Cyp1a1Ren2 rat. PloS one, 2021, Volume: 16, Issue:11 Topics: Animals; Antifibrotic Agents; Cytochrome P-450 CYP1A1; Disease Progression; Fibrosis; Heart; Hyperte	2021
The effect of spironolactone on thyroid autoimmunity in euthyroid men with Hashimoto's thyroiditis. Journal of clinical pharmacy and therapeutics, 2020, Volume: 45, Issue:1 Topics: Aged; Disease Progression; Diuretics; Dose-Response Relationship, Drug; Hashimoto Disease; Humans; M	2020
Spironolactone use is associated with improved outcomes in heart failure with mid-range ejection fraction. ESC heart failure, 2020, Volume: 7, Issue:1 Topics: Aged; Disease Progression; Female; Follow-Up Studies; Heart Failure; Humans; Male; Mineralocorticoid	2020
Disease characteristics and outcomes in patients with chronic kidney disease and type 2 diabetes: a matched cohort study of spironolactone users and non-users. BMC nephrology, 2020, 02-26, Volume: 21, Issue:1 Topics: Adult; Aged; Aged, 80 and over; Comorbidity; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Dise	2020
Use of urinary proteomics in diagnosis and monitoring of diabetic kidney disease. The lancet. Diabetes & endocrinology, 2020, Volume: 8, Issue:4 Topics: Diabetes Mellitus; Diabetic Nephropathies; Disease Progression; Humans; Prospective Studies; Proteom	2020
CHA2DS2-VASc and ATRIA Scores and Clinical Outcomes in Patients with Heart Failure with Preserved Ejection Fraction. Cardiovascular drugs and therapy, 2020, Volume: 34, Issue:6 Topics: Aged; Aged, 80 and over; Cause of Death; Clinical Trials, Phase III as Topic; Decision Support Techn	2020
MitraClip or Ventricular Assist Device? International heart journal, 2020, Nov-28, Volume: 61, Issue:6 Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Cardiac Resynchronization The	2020
Efficacy of tolvaptan for the patients with advanced hepatocellular carcinoma. World journal of gastroenterology, 2017, Aug-07, Volume: 23, Issue:29 Topics: Aged; Aged, 80 and over; Antidiuretic Hormone Receptor Antagonists; Ascites; Benzazepines; Body Weig	2017
Smooth Muscle Cell-Mineralocorticoid Receptor as a Mediator of Cardiovascular Stiffness With Aging. Hypertension (Dallas, Tex. : 1979), 2018, Volume: 71, Issue:4 Topics: Aged; Animals; Cellular Senescence; Disease Progression; Exercise Tolerance; Fibrosis; Gene Expressi	2018
Delayed spironolactone administration prevents the transition from acute kidney injury to chronic kidney disease through improving renal inflammation. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association, 2019, 05-01, Volume: 34, Issue:5 Topics: Acute Kidney Injury; Animals; Delayed-Action Preparations; Disease Models, Animal; Disease Progressi	2019
Abiraterone and spironolactone in prostate cancer: a combination to avoid. Acta clinica Belgica, 2019, Volume: 74, Issue:6 Topics: Abiraterone Acetate; Aged, 80 and over; Antineoplastic Agents; Bone Neoplasms; Contraindications, Dr	2019
Efficacy and Safety of Spironolactone in Patients With HFpEF and Chronic Kidney Disease. JACC. Heart failure, 2019, Volume: 7, Issue:1 Topics: Aged; Aged, 80 and over; Cardiovascular Diseases; Comorbidity; Deprescriptions; Disease Progression;	2019
Protective effects of selective mineralocorticoid receptor antagonist against aortic aneurysm progression in a novel murine model. The Journal of surgical research, 2013, Volume: 185, Issue:1 Topics: Animals; Aortic Aneurysm; Blood Pressure; Chemokine CCL2; Disease Models, Animal; Disease Progressio	2013
Heart failure with systolic dysfunction complicating acute myocardial infarction - differential outcomes but similar eplerenone efficacy by ST-segment or non-ST-segment elevation: A post hoc substudy of the EPHESUS trial. Archives of cardiovascular diseases, 2014, Volume: 107, Issue:3 Topics: Aged; Cardiovascular Agents; Cardiovascular Diseases; Cause of Death; Comorbidity; Coronary Thrombos	2014
Protective cardiorenal effects of spironolactone in a rodent model of polycystic kidney disease. Clinical and experimental pharmacology & physiology, 2015, Volume: 42, Issue:4 Topics: Animals; Aorta; Biomarkers; Blood Pressure; Cytoprotection; Disease Models, Animal; Disease Progress	2015
A cold taken to heart. Circulation, 2015, May-12, Volume: 131, Issue:19 Topics: Adenoviridae Infections; Adult; Biopsy; Cardiovascular Agents; Combined Modality Therapy; Defibrilla	2015
Spironolactone ameliorates arterial medial calcification in uremic rats: the role of mineralocorticoid receptor signaling in vascular calcification. American journal of physiology. Renal physiology, 2015, Dec-01, Volume: 309, Issue:11 Topics: Adenine; Animals; Aorta, Abdominal; Aortic Diseases; Apoptosis; Biomarkers; Disease Models, Animal;	2015
Association between long-term prescription of aldosterone antagonist and the progression of heart failure with preserved ejection fraction in hypertensive patients. International journal of cardiology, 2016, Oct-01, Volume: 220 Topics: Antihypertensive Agents; Cardiotonic Agents; Cohort Studies; Disease Progression; Drug Administratio	2016
Symptomatic Cushing's syndrome and hyperandrogenemia in a steroid cell ovarian neoplasm: a case report. Journal of medical case reports, 2016, Oct-12, Volume: 10, Issue:1 Topics: Aged; Antineoplastic Agents, Hormonal; Cushing Syndrome; Disease Progression; Fatal Outcome; Female;	2016
Blood pressure versus direct mineralocorticoid effects on kidney inflammation and fibrosis in DOCA-salt hypertension. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association, 2008, Volume: 23, Issue:11 Topics: Animals; Antihypertensive Agents; Blood Pressure; Desoxycorticosterone; Disease Models, Animal; Dise	2008
The effect of aldosterone antagonist in experimental nephropathy induced by cyclosporine A. Renal failure, 2008, Volume: 30, Issue:4 Topics: Animals; Creatinine; Cyclosporine; Disease Models, Animal; Disease Progression; Glomerular Filtratio	2008
Clinical factors affecting serum potassium concentration in cardio-renal decompensation syndrome. International journal of cardiology, 2010, Jan-21, Volume: 138, Issue:2 Topics: Adolescent; Adult; Aged; Aged, 80 and over; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Con	2010
Safety of spironolactone use in ambulatory heart failure patients. Clinical cardiology, 2008, Volume: 31, Issue:11 Topics: Aged; Ambulatory Care; Biomarkers; Cohort Studies; Creatinine; Disease Progression; Diuretics; Femal	2008
Cardiac magnetic resonance imaging and management of dilated cardiomyopathy in a Duchenne muscular dystrophy manifesting carrier. Journal of neurology, 2009, Volume: 256, Issue:2 Topics: Adult; Biomarkers; Carbazoles; Cardiomyopathy, Dilated; Carvedilol; Child; Creatine Kinase; Disease	2009
Aldosterone receptor inhibition alters the viscoelastic biomechanical behavior of the aortic wall. Experimental biology and medicine (Maywood, N.J.), 2010, Volume: 235, Issue:3 Topics: Aldosterone; Animals; Aorta; Biomechanical Phenomena; Blood Pressure; Disease Progression; Elasticit	2010
Microvascular tissue perfusion is impaired in acutely decompensated heart failure and improves following standard treatment. European journal of heart failure, 2011, Volume: 13, Issue:7 Topics: Adrenergic beta-Antagonists; Aged; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme I	2011
Long-term mineralocorticoid receptor blockade ameliorates progression of experimental diabetic renal disease. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association, 2012, Volume: 27, Issue:3 Topics: Aldosterone; Animals; Blood Pressure; Blotting, Western; Collagen Type IV; Diabetes Mellitus, Experi	2012
Chronic antagonism of the mineralocorticoid receptor ameliorates hypertension and end organ damage in a rodent model of salt-sensitive hypertension. Clinical and experimental hypertension (New York, N.Y. : 1993), 2011, Volume: 33, Issue:8 Topics: Aldosterone; Animals; Blood Pressure; Chronic Disease; Creatinine; Disease Models, Animal; Disease P	2011
Matrix metalloproteinase 2 induces epithelial-mesenchymal transition in proximal tubules from the luminal side and progresses fibrosis in mineralocorticoid/salt-induced hypertensive rats. Journal of hypertension, 2011, Volume: 29, Issue:12 Topics: Animals; Collagen; Desoxycorticosterone; Disease Models, Animal; Disease Progression; Drug Therapy,	2011
Permanent muscular sodium overload and persistent muscle edema in Duchenne muscular dystrophy: a possible contributor of progressive muscle degeneration. Journal of neurology, 2012, Volume: 259, Issue:11 Topics: Adolescent; Child; Disease Progression; Edema; Eplerenone; Female; Follow-Up Studies; Humans; Male;	2012
Renoprotective effects of mineralocorticoid receptor blockers in patients with proteinuric kidney diseases. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association, 2013, Volume: 28, Issue:2 Topics: Adult; Aged; Aged, 80 and over; Blood Pressure; Cohort Studies; Comorbidity; Disease Progression; Fe	2013
Eplerenone reduced lesion size in early but not advanced atherosclerosis in apolipoprotein E-deficient mice. Journal of cardiovascular pharmacology, 2012, Volume: 60, Issue:6 Topics: Animals; Aorta, Thoracic; Aortic Diseases; Apolipoproteins E; Atherosclerosis; Cytochrome P-450 CYP1	2012
Effects of long-term monotherapy with eplerenone, a novel aldosterone blocker, on progression of left ventricular dysfunction and remodeling in dogs with heart failure. Circulation, 2002, Dec-03, Volume: 106, Issue:23 Topics: Administration, Oral; Animals; Chronic Disease; Disease Models, Animal; Disease Progression; Dogs; E	2002
Aldosteronism and peripheral blood mononuclear cell activation: a neuroendocrine-immune interface. Circulation research, 2003, Nov-14, Volume: 93, Issue:10 Topics: Aldosterone; Animals; Calcium; Cell Separation; Coronary Vessels; Disease Models, Animal; Disease Pr	2003
[Myasthenia gravis and pregnancy: clinical course and management of delivery and the postpartum phase]. Revue neurologique, 2006, Volume: 162, Issue:3 Topics: Abortion, Therapeutic; Adult; Autoantibodies; Autoantigens; Cholinesterase Inhibitors; Delivery, Obs	2006
Life-threatening Pneumocystis jiroveci pneumonia following treatment of severe Cushing's syndrome. The Netherlands journal of medicine, 2007, Volume: 65, Issue:6 Topics: Cushing Syndrome; Disease Progression; Fatal Outcome; Female; Humans; Ketoconazole; Middle Aged; Mif	2007
The role of aldosterone blockade in murine lupus nephritis. Arthritis research & therapy, 2008, Volume: 10, Issue:1 Topics: Animals; Antigen-Antibody Complex; Autoantibodies; Disease Progression; Female; Gene Expression; Kid	2008
Aldosterone modulates plasminogen activator inhibitor-1 and glomerulosclerosis in vivo. Kidney international, 2000, Volume: 58, Issue:3 Topics: Aldosterone; Angiotensin II; Animals; Blood Pressure; Blotting, Northern; Creatinine; Disease Progre	2000
Epidemiology and pathophysiology of heart failure. Current cardiology reports, 2000, Volume: 2, Issue:3 Topics: Aldosterone; Angiotensin-Converting Enzyme Inhibitors; Clinical Trials as Topic; Disease Progression	2000
[Management of bronchiolitis in the infant. Recommendations. Long text]. Archives de pediatrie : organe officiel de la Societe francaise de pediatrie, 2001, Volume: 8 Suppl 1 Topics: Acute Disease; Anti-Inflammatory Agents; Antiviral Agents; Bronchiolitis, Viral; Bronchodilator Agen	2001