spironolactone and Cardiovascular Diseases 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.

Cardiovascular Diseases: Pathological conditions involving the CARDIOVASCULAR SYSTEM including the HEART; the BLOOD VESSELS; or the PERICARDIUM.

Research Excerpts

Excerpt	Relevance	Reference
"This study sought to investigate sex differences in outcomes and responses to spironolactone in patients with heart failure with preserved ejection fraction (HFpEF)."	9.30	Sex Differences in Outcomes and Responses to Spironolactone in Heart Failure With Preserved Ejection Fraction: A Secondary Analysis of TOPCAT Trial. ( Kao, DP; Lindenfeld, J; Merrill, M; Sweitzer, NK, 2019)
"In this randomized, double-blind trial, we assigned 3445 patients with symptomatic heart failure and a left ventricular ejection fraction of 45% or more to receive either spironolactone (15 to 45 mg daily) or placebo."	9.19	Spironolactone for heart failure with preserved ejection fraction. ( Anand, IS; Assmann, SF; Boineau, R; Claggett, B; Clausell, N; Desai, AS; Diaz, R; Fleg, JL; Gordeev, I; Harty, B; Heitner, JF; Kenwood, CT; Lewis, EF; McKinlay, SM; O'Meara, E; Pfeffer, MA; Pitt, B; Probstfield, JL; Shaburishvili, T; Shah, SJ; Solomon, SD; Sweitzer, NK; Yang, S, 2014)
"Eplerenone, as compared with placebo, reduced both the risk of death and the risk of hospitalization among patients with systolic heart failure and mild symptoms."	9.15	Eplerenone in patients with systolic heart failure and mild symptoms. ( Krum, H; McMurray, JJ; Pitt, B; Pocock, SJ; Shi, H; Swedberg, K; van Veldhuisen, DJ; Vincent, J; Zannad, F, 2011)
" A randomized controlled trial of patients with heart failure and an ejection fraction > 45% showed that spironolactone did not significantly reduce the incidence of the primary composite outcome of death from cardiovascular causes, aborted cardiac arrest, or hospitalization for the management of heart failure."	8.93	Clinical Question: In congestive heart failure patients with preserved ejection fraction, does spironolactone improve cardiac outcomes? ( Onarecker, C, 2016)
"Adult Wistar rats were randomly distributed into 4 groups; controls, spironolactone treated rats (Spir, 50mg/kg/day), hyperthyroid rats (Hyper, daily intraperitoneal levothyroxine 0."	7.96	The Impact of Spironolactone on Markers of Myocardial Oxidative Status, Inflammation and Remodeling in Hyperthyroid Rats. ( Aljohmani, AI; Alzoubi, KH; Mayyas, FA, 2020)
"The TOPCAT (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist Trial) trial randomized patients with HFpEF and either prior hospitalization for HF or elevated natriuretic peptide levels (B-type NP [BNP] ≥100 pg/ml or N-terminal proBNP ≥360 pg/ml) to spironolactone or placebo."	7.85	Interaction Between Spironolactone and Natriuretic Peptides in Patients With Heart Failure and Preserved Ejection Fraction: From the TOPCAT Trial. ( Anand, IS; Claggett, B; Desai, AS; Fleg, JL; Liu, J; O'Meara, E; Pfeffer, MA; Pitt, B; Rector, TS; Shah, AM; Shah, SJ; Solomon, SD, 2017)
" Thus, the primary objective of this study was to assess the effects on arterial function and structure of an OC containing chlormadinone acetate (2 mg) and ethinylestradiol (30 mcg), alone or combined with spironolactone (OC+SPL), in patients with PCOS."	6.77	The effects of 2 mg chlormadinone acetate/30 mcg ethinylestradiol, alone or combined with spironolactone, on cardiovascular risk markers in women with polycystic ovary syndrome. ( de Sá, MF; dos Reis, RM; Fernandes, JB; Ferriani, RA; Martins, WP; Soares, GM; Vieira, CS, 2012)
"Vascular calcification is frequently found already in early stages of chronic kidney disease (CKD) patients and is associated with high cardiovascular risk."	6.50	Impact of aldosterone on osteoinductive signaling and vascular calcification. ( Alesutan, I; Lang, F; Ritz, E; Voelkl, J, 2014)
"Eplerenone is a selective mineralocorticoid receptor antagonist."	5.91	Role of eplerenone in the threatment of cardiovascular diseases. ( Málek, F, 2023)
" Longer duration or higher dosage of spironolactone seems to be more effective in improving cardiovascular system status in PD patients."	5.46	Aldosterone antagonist therapy and its relationship with inflammation, fibrosis, thrombosis, mineral-bone disorder and cardiovascular complications in peritoneal dialysis (PD) patients. ( Donderski, R; Grajewska, M; Manitius, J; Miśkowiec, I; Odrowąż-Sypniewska, G; Siódmiak, J; Stefańska, A; Stróżecki, P; Sulikowska, B, 2017)
"For 1761 participants from North and South America enrolled in the multicenter, double-blinded Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist randomized clinical trial of spironolactone for patients with HFpEF between August 10, 2006, and January 31, 2012, the association of baseline β-blocker use with HF hospitalization and CVD mortality was analyzed using unadjusted and adjusted Cox proportional hazards regression models, overall and in strata of patients with an EF of 50% or greater or less than 50%."	5.30	Association of β-Blocker Use With Heart Failure Hospitalizations and Cardiovascular Disease Mortality Among Patients With Heart Failure With a Preserved Ejection Fraction: A Secondary Analysis of the TOPCAT Trial. ( Callas, PW; Dougherty, GB; Infeld, M; Juraschek, SP; Meyer, M; Plante, TB; Silverman, DN, 2019)
"This study sought to investigate sex differences in outcomes and responses to spironolactone in patients with heart failure with preserved ejection fraction (HFpEF)."	5.30	Sex Differences in Outcomes and Responses to Spironolactone in Heart Failure With Preserved Ejection Fraction: A Secondary Analysis of TOPCAT Trial. ( Kao, DP; Lindenfeld, J; Merrill, M; Sweitzer, NK, 2019)
"This study assessed the relationship between atrial fibrillation (AF) and outcomes in the TOPCAT (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist) trial, to evaluate whether AF modified the treatment response to spironolactone and whether spironolactone influenced post-randomization AF."	5.27	Atrial Fibrillation in Heart Failure With Preserved Ejection Fraction: The TOPCAT Trial. ( Anand, IS; Cikes, M; Claggett, B; Desai, AS; Fang, JC; Lewis, EF; O'Meara, E; Pfeffer, MA; Pitt, B; Rouleau, JL; Saksena, S; Shah, AM; Shah, SJ; Solomon, SD; Sweitzer, NK, 2018)
"In this randomized, double-blind trial, we assigned 3445 patients with symptomatic heart failure and a left ventricular ejection fraction of 45% or more to receive either spironolactone (15 to 45 mg daily) or placebo."	5.19	Spironolactone for heart failure with preserved ejection fraction. ( Anand, IS; Assmann, SF; Boineau, R; Claggett, B; Clausell, N; Desai, AS; Diaz, R; Fleg, JL; Gordeev, I; Harty, B; Heitner, JF; Kenwood, CT; Lewis, EF; McKinlay, SM; O'Meara, E; Pfeffer, MA; Pitt, B; Probstfield, JL; Shaburishvili, T; Shah, SJ; Solomon, SD; Sweitzer, NK; Yang, S, 2014)
"Eplerenone, as compared with placebo, reduced both the risk of death and the risk of hospitalization among patients with systolic heart failure and mild symptoms."	5.15	Eplerenone in patients with systolic heart failure and mild symptoms. ( Krum, H; McMurray, JJ; Pitt, B; Pocock, SJ; Shi, H; Swedberg, K; van Veldhuisen, DJ; Vincent, J; Zannad, F, 2011)
" A randomized controlled trial of patients with heart failure and an ejection fraction > 45% showed that spironolactone did not significantly reduce the incidence of the primary composite outcome of death from cardiovascular causes, aborted cardiac arrest, or hospitalization for the management of heart failure."	4.93	Clinical Question: In congestive heart failure patients with preserved ejection fraction, does spironolactone improve cardiac outcomes? ( Onarecker, C, 2016)
" Hyperaldosteronism due to klotho deficiency results in vascular calcification, which can be mitigated by spironolactone treatment."	4.90	Aldosterone and parathyroid hormone interactions as mediators of metabolic and cardiovascular disease. ( Fahrleitner-Pammer, A; Gaksch, M; Grübler, M; Kienreich, K; Kraigher-Krainer, E; März, W; Mrak, P; Pieske, B; Pilz, S; Ritz, E; Rus-Machan, J; Tomaschitz, A; Toplak, H; Verheyen, N, 2014)
" Eplerenone, a mineralocorticoid-receptor antagonist with minimal binding to the progesterone and androgen receptors, is now licensed for treatment of heart failure in Europe and heart failure and hypertension in the US; it has also been proposed as a treatment for a variety of cardiovascular conditions."	4.84	Drug Insight: eplerenone, a mineralocorticoid-receptor antagonist. ( Connell, JM; McInnes, GT; McManus, F, 2008)
" However, although aldosterone receptor antagonism reduces mortality in patients with congestive heart failure, the progestational and antiandrogenic side effects of the nonspecific aldosterone receptor antagonist, spironolactone, have limited its usefulness in the treatment of hypertension."	4.82	Eplerenone: cardiovascular protection. ( Brown, NJ, 2003)
"Eplerenone is a selective aldosterone blocker that effectively lowers BP in both white and black patients with hypertension and provides meaningful further antihypertensive efficacy when added to patients whose hypertension is inadequately controlled by angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers."	4.81	Clinical implications of aldosterone blockade. ( Weber, MA, 2002)
" Emerging evidence from an extensive development program for eplerenone (Pharmacia Corp), a novel selective aldosterone receptor antagonist, may further expand the evidence base for aldosterone receptor antagonism, including its potential in treating hypertension."	4.81	The role of aldosterone receptor blockade in the management of cardiovascular disease. ( Krum, H; Liew, D, 2002)
"Among patients with DKD and hypertension, the short-term use of MRAs, either spironolactone or eplerenone, in combination with ACEI/ARBs, was not associated with lower risk of cardiovascular or kidney outcomes compared with ACEI/ARB monotherapy."	4.02	Cardiovascular and kidney outcomes of spironolactone or eplerenone in combination with ACEI/ARBs in patients with diabetic kidney disease. ( An, J; Niu, F; Sim, JJ, 2021)
"Adult Wistar rats were randomly distributed into 4 groups; controls, spironolactone treated rats (Spir, 50mg/kg/day), hyperthyroid rats (Hyper, daily intraperitoneal levothyroxine 0."	3.96	The Impact of Spironolactone on Markers of Myocardial Oxidative Status, Inflammation and Remodeling in Hyperthyroid Rats. ( Aljohmani, AI; Alzoubi, KH; Mayyas, FA, 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)
"Patient data were pooled from the CHARM-Preserved (Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity), I-PRESERVE (Irbesartan in Heart Failure with Preserved Ejection Fraction), and TOPCAT (Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist trial) studies and were examined for the association between having a pacemaker and the risk of the primary composite of cardiovascular death or HF hospitalization, the individual components of the composite, the 2 main modes of cardiovascular death (i."	3.91	Prior Pacemaker Implantation and Clinical Outcomes in Patients With Heart Failure and Preserved Ejection Fraction. ( Anand, IS; Carson, PE; Desai, AS; Docherty, KF; Granger, CB; Jhund, PS; Komajda, M; McKelvie, RS; McMurray, JJV; Petrie, MC; Pfeffer, MA; Shen, L; Solomon, SD; Swedberg, K; Zile, MR, 2019)
"The TOPCAT (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist Trial) trial randomized patients with HFpEF and either prior hospitalization for HF or elevated natriuretic peptide levels (B-type NP [BNP] ≥100 pg/ml or N-terminal proBNP ≥360 pg/ml) to spironolactone or placebo."	3.85	Interaction Between Spironolactone and Natriuretic Peptides in Patients With Heart Failure and Preserved Ejection Fraction: From the TOPCAT Trial. ( Anand, IS; Claggett, B; Desai, AS; Fleg, JL; Liu, J; O'Meara, E; Pfeffer, MA; Pitt, B; Rector, TS; Shah, AM; Shah, SJ; Solomon, SD, 2017)
"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)
"Gynecomastia was rare and did not differ significantly between groups."	2.90	Safety and cardiovascular efficacy of spironolactone in dialysis-dependent ESRD (SPin-D): a randomized, placebo-controlled, multiple dosage trial. ( Anderson, AH; Charytan, DM; Dember, LM; DiCarli, M; Himmelfarb, J; Hsu, JY; Hung, AM; Ikizler, TA; Kimmel, PL; Kliger, AS; Landis, JR; Mehrotra, R; Raj, DS; Sharma, S; Skali, H; Weiner, DE; Williams, M, 2019)
" Thus, the primary objective of this study was to assess the effects on arterial function and structure of an OC containing chlormadinone acetate (2 mg) and ethinylestradiol (30 mcg), alone or combined with spironolactone (OC+SPL), in patients with PCOS."	2.77	The effects of 2 mg chlormadinone acetate/30 mcg ethinylestradiol, alone or combined with spironolactone, on cardiovascular risk markers in women with polycystic ovary syndrome. ( de Sá, MF; dos Reis, RM; Fernandes, JB; Ferriani, RA; Martins, WP; Soares, GM; Vieira, CS, 2012)
"Vascular calcification is frequently found already in early stages of chronic kidney disease (CKD) patients and is associated with high cardiovascular risk."	2.50	Impact of aldosterone on osteoinductive signaling and vascular calcification. ( Alesutan, I; Lang, F; Ritz, E; Voelkl, J, 2014)
"Hyperkalemia is the main potential side effect of eplerenone, especially when used in combination with other medications that can cause hyperkalemia."	2.46	Review article: eplerenone: an underused medication? ( Abuannadi, M; O'Keefe, JH, 2010)
"Aldosterone plays an important role in the pathophysiology of sodium/potassium and water homeostasis of the body."	2.43	Cardiovascular effects of aldosterone. ( Murin, J, 2005)
"Although insulin resistance is not part of the diagnostic criteria for PCOS, its importance in the pathogenesis of PCOS can not be denied."	2.43	Insulin resistance in polycystic ovarian disease. ( Bhatia, V, 2005)
"Aldosterone is a mineralocorticoid primarily produced in the zona glomerulosa of the adrenal gland."	2.43	Aldosterone receptor antagonists and cardiovascular disease: do we need a change of the guard? ( Dostal, DE; Jewell, CW; Mock, J; Watson, LE, 2006)
"Aldosterone has been overlooked as a mediator of RAAS escape and a key factor in target-organ injury despite the use of available RAAS blockers."	2.42	RAAS escape: a real clinical entity that may be important in the progression of cardiovascular and renal disease. ( Lakkis, J; Lu, WX; Weir, MR, 2003)
"Aldosterone has attracted considerable interest as an independent cardiovascular risk marker, which has been demonstrated in a number of studies."	2.42	Rapid effects of aldosterone on vascular cells: clinical implications. ( Boldyreff, B; Lösel, R; Schultz, A; Wehling, M, 2004)
"Eplerenone is a selective mineralocorticoid receptor antagonist."	1.91	Role of eplerenone in the threatment of cardiovascular diseases. ( Málek, F, 2023)
" Longer duration or higher dosage of spironolactone seems to be more effective in improving cardiovascular system status in PD patients."	1.46	Aldosterone antagonist therapy and its relationship with inflammation, fibrosis, thrombosis, mineral-bone disorder and cardiovascular complications in peritoneal dialysis (PD) patients. ( Donderski, R; Grajewska, M; Manitius, J; Miśkowiec, I; Odrowąż-Sypniewska, G; Siódmiak, J; Stefańska, A; Stróżecki, P; Sulikowska, B, 2017)
" The main difficulty in choosing the proper therapeutic regimen consists in the lack of suitable dosing guidelines with adapted therapeutic targets for the older multimorbid population, usually not represented in the large controlled trials forming the basis of general recommendations."	1.42	[Cardiovascular drugs in aged and multimorbid patients]. ( Follath, F, 2015)
"Patients with primary aldosteronism were compared with patients with essential hypertension and were treated to reach a blood pressure of less than 140/90 mm Hg."	1.35	Cardiovascular outcomes in patients with primary aldosteronism after treatment. ( Baroselli, S; Catena, C; Chiuch, A; Colussi, G; Lapenna, R; Nadalini, E; Sechi, LA, 2008)
"Spironolactone treatment decreased PAI-1 immunoreactivity and reduced in a dose-dependent fashion cardiac and renal damage."	1.32	Aldosterone and not plasminogen activator inhibitor-1 is a critical mediator of early angiotensin II/NG-nitro-L-arginine methyl ester-induced myocardial injury. ( Adler, GK; Jonasson, L; Martinez-Vasquez, D; Mukasa, K; Oestreicher, EM; Roubsanthisuk, W; Stone, JR, 2003)
"Hirsutism is the manifestation of hyperandrogenemia in PCOS."	1.32	The treatment of polycystic ovary syndrome. ( Ajossa, S; Guerriero, S; Melis, GB; Orrù, M; Paoletti, AM, 2004)

Research

Studies (98)

Authors

Clinical Trials (33)

Trial Overview

Trial Outcomes

Safety - Cardiovascular Death

Timeframe	Studies, this research(%)	All Research%
pre-1990	6 (6.12)	18.7374
1990's	4 (4.08)	18.2507
2000's	37 (37.76)	29.6817
2010's	43 (43.88)	24.3611
2020's	8 (8.16)	2.80

Authors	Studies
An, J	1
Niu, F	1
Sim, JJ	1
Málek, F	1
Ding, K	1
Li, Z	1
Lu, Y	1
Sun, L	1
Mayyas, FA	1
Aljohmani, AI	1
Alzoubi, KH	1
Silverman, DN	1
Plante, TB	1
Infeld, M	1
Callas, PW	1
Juraschek, SP	1
Dougherty, GB	1
Meyer, M	1
Kuno, T	1
Ueyama, H	1
Fujisaki, T	1
Briasouli, A	1
Takagi, H	1
Briasoulis, A	1
Agarwal, A	1
Cheung, AK	1
Rahimi, G	1
Tecson, KM	1
Elsaid, O	1
McCullough, PA	1
Hasegawa, T	1
Nishiwaki, H	1
Ota, E	1
Levack, WM	1
Noma, H	1
Anand, IS	5
Claggett, B	4
Liu, J	1
Shah, AM	2
Rector, TS	1
Shah, SJ	4
Desai, AS	6
O'Meara, E	5
Fleg, JL	3
Pfeffer, MA	6
Pitt, B	9
Solomon, SD	6
Donderski, R	1
Stróżecki, P	1
Sulikowska, B	1
Grajewska, M	1
Miśkowiec, I	1
Stefańska, A	1
Siódmiak, J	1
Odrowąż-Sypniewska, G	1
Manitius, J	1
Onarecker, C	1
Cikes, M	1
Lewis, EF	4
Rouleau, JL	1
Sweitzer, NK	3
Fang, JC	3
Saksena, S	1
Muneyyirci-Delale, O	1
Co, S	1
Winer, N	1
Charytan, DM	1
Himmelfarb, J	1
Ikizler, TA	1
Raj, DS	1
Hsu, JY	1
Landis, JR	1
Anderson, AH	1
Hung, AM	1
Mehrotra, R	1
Sharma, S	1
Weiner, DE	1
Williams, M	1
DiCarli, M	1
Skali, H	1
Kimmel, PL	1
Kliger, AS	1
Dember, LM	1
Beldhuis, IE	1
Myhre, PL	1
Damman, K	1
Voors, AA	1
Grodin, JL	1
Philips, S	1
Mullens, W	1
Nijst, P	1
Martens, P	1
Drazner, MH	1
Tang, WHW	1
Pandey, A	1
Merrill, M	1
Lindenfeld, J	1
Kao, DP	1
Shen, L	1
Jhund, PS	1
Docherty, KF	1
Petrie, MC	1
Carson, PE	1
Granger, CB	1
Komajda, M	1
McKelvie, RS	1
Swedberg, K	2
Zile, MR	1
McMurray, JJV	1
Ocello, A	1
La Rosa, S	1
Fiorini, F	1
Randone, S	1
Maccarrone, R	1
Battaglia, G	1
Granata, A	1
Patel, BM	2
Kakadiya, J	1
Goyal, RK	2
Mehta, AA	2
Bhadada, SV	1
Tomaschitz, A	2
Ritz, E	2
Pieske, B	1
Rus-Machan, J	1
Kienreich, K	1
Verheyen, N	1
Gaksch, M	1
Grübler, M	1
Fahrleitner-Pammer, A	1
Mrak, P	1
Toplak, H	1
Kraigher-Krainer, E	1
März, W	2
Pilz, S	2
Matsumoto, Y	1
Mori, Y	1
Kageyama, S	1
Arihara, K	1
Sugiyama, T	1
Ohmura, H	1
Yakushigawa, T	1
Sugiyama, H	1
Shimada, Y	1
Nojima, Y	1
Shio, N	1
Rossignol, P	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
Assmann, SF	1
Boineau, R	1
Clausell, N	1
Diaz, R	1
Gordeev, I	1
Harty, B	1
Heitner, JF	1
Kenwood, CT	1
Probstfield, JL	1
Shaburishvili, T	1
Yang, S	1
McKinlay, SM	1
Maggioni, AP	1
Ng, KP	2
Jain, P	2
Heer, G	2
Redman, V	1
Chagoury, OL	1
Dowswell, G	1
Greenfield, S	2
Freemantle, N	2
Townend, JN	2
Gill, PS	2
McManus, RJ	2
Ferro, CJ	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
Kannan, A	1
Poongkunran, C	1
Balamuthusamy, S	1
Lang, F	1
Alesutan, I	1
Voelkl, J	1
Stewart Coats, AJ	1
Shewan, L	1
Lin, C	1
Zhang, Q	1
Zhang, H	1
Lin, A	1
Follath, F	1
Pieper, PG	1
Joseph, J	1
Claggett, BC	1
Huynh, T	1
Mckinlay, S	1
van den Berg, TN	1
van Swieten, HA	1
Vos, JC	1
Verweij, V	1
Wouterse, AC	1
Deinum, J	1
Morshuis, WJ	1
Rongen, GA	1
Riksen, NP	1
Quach, K	1
Lvtvyn, L	1
Baigent, C	1
Bueti, J	1
Garg, AX	1
Hawley, C	1
Haynes, R	1
Manns, B	1
Perkovic, V	1
Rabbat, CG	1
Wald, R	1
Walsh, M	1
Zhao, JV	1
Xu, L	1
Lin, SL	1
Schooling, CM	1
Saran, R	1
Trzaska, E	1
Gumułka, W	1
Makulska-Nowak, HE	1
Goyal, BR	1
Solanki, N	1
Abuannadi, M	1
O'Keefe, JH	1
Armstrong, PW	1
McMurray, JJ	1
Krum, H	3
van Veldhuisen, DJ	1
Shi, H	1
Pocock, SJ	2
Gus, M	1
Fuchs, FD	1
Ariti, CA	1
Collier, TJ	1
Wang, D	1
Vieira, CS	1
Martins, WP	1
Fernandes, JB	1
Soares, GM	1
dos Reis, RM	1
de Sá, MF	1
Ferriani, RA	1
Watanabe, M	1
dos Santos, PP	1
Nogueira, BF	1
Rafacho, BP	1
Azevedo, PS	1
Polegato, BF	1
Chiuso-Minicucci, F	1
Bonomo, C	1
Roscani, MG	1
Zorzella-Pezavento, SF	1
Tanni, SE	1
Pereira, EJ	1
Okoshi, MP	1
Paiva, SA	1
Zornoff, LA	1
Minicucci, MF	1
Rocha, R	1
Funder, JW	2
Weber, MA	1
Liew, D	1
Brown, NJ	1
Lakkis, J	1
Lu, WX	1
Weir, MR	1
Epstein, M	2
POLIANTSEVA, LR	1
ERMOLENKO, VM	1
Oestreicher, EM	1
Martinez-Vasquez, D	1
Stone, JR	1
Jonasson, L	1
Roubsanthisuk, W	1
Mukasa, K	1
Adler, GK	1
Ajossa, S	1
Guerriero, S	1
Paoletti, AM	1
Orrù, M	1
Melis, GB	1
Struthers, AD	1
MacDonald, TM	2
Christ, M	1
Grimm, W	1
Maisch, B	1
Black, HR	1
Garthwaite, SM	1
McMahon, EG	1
Ménard, J	1
Miyamori, I	2
Soto, GE	1
Jones, P	1
Weintraub, WS	1
Krumholz, HM	1
Spertus, JA	1
Lösel, R	1
Schultz, A	1
Boldyreff, B	1
Wehling, M	1
Murin, J	1
Krysiak, R	1
Okopień, B	1
Herman, ZS	1
Bhatia, V	1
Fleischman, A	1
Mansfield, J	1
Mulatero, P	1
Milan, A	1
Williams, TA	1
Veglio, F	1
Jewell, CW	1
Watson, LE	1
Mock, J	1
Dostal, DE	1
Simorre, B	1
Kawai, Y	1
Fan, CY	1
Parthasarathy, HK	1
Nishiyama, A	1
Kusaka, T	1
Kitajima, H	1
Nagata, D	1
Hirata, Y	1
McManus, F	1
McInnes, GT	1
Connell, JM	1
Catena, C	1
Colussi, G	1
Nadalini, E	1
Chiuch, A	1
Baroselli, S	1
Lapenna, R	1
Sechi, LA	1
Jolobe, OM	1
Lovejoy, JC	1
Bray, GA	1
Bourgeois, MO	1
Macchiavelli, R	1
Rood, JC	1
Greeson, C	1
Partington, C	1
Delyani, JA	1
Fiebeler, A	1
Schmidt, F	1
Müller, DN	1
Park, JK	1
Dechend, R	1
Bieringer, M	1
Shagdarsuren, E	1
Breu, V	1
Haller, H	1
Luft, FC	1
Rossi, GP	1
Cavallin, M	1
Nussdorfer, GG	1
Pessina, AC	1
Wilhelmsen, L	1
Berglund, G	1
Sannerstedt, R	1
Hansson, L	1
Andersson, O	1
Sievertsson, R	1
Wikstrand, J	1
Guthrie, GP	1
Genest, J	1
Kuchel, O	1
Kaesemeyer, WH	1
Prisant, LM	1
Carr, AA	1
Taniguchi, S	1
Kurokawa, K	1
Larcan, A	1
Calamai, M	1
Jacob, F	1
Gardell, C	1
Tuchweber, B	1
Hatakeyama, S	1
Kovacs, K	1
Steigmann, F	1
Oz, R	1
Dubin, A	1

Trial	Phase	Enrollment	Study Type	Start Date	Status
Improving Outcomes in Atrial Fibrillation Patients Aided by Implantable Cardiac Monitor: Evaluation of Chronic Beta-blocker Use Versus As-needed Pharmacological Rate Control[NCT05745337]	Phase 1	20 participants (Anticipated)	Interventional	2023-02-06	Recruiting
A Randomized, Controlled Trial of L-arginine and Spironolactone in Dialysis-dependant End Stage Renal Disease[NCT01855334]	Phase 4	0 participants (Actual)	Interventional	2013-09-30	Withdrawn (stopped due to change of funding leading to major redesign)
Effect of Spironolactone on the Progression of Coronary Calcification in Peritoneal Dialysis Patients[NCT03314493]	Phase 3	33 participants (Actual)	Interventional	2014-11-07	Completed
Protective Mechanisms of Aldosterone Antagonists and Their Effects on Cardiovascular Damage in Chronic Renal Failure: Clinical and Experimental Studies[NCT00277693]	Phase 4	0 participants	Interventional		Recruiting
Aldosterone bloCkade for Health Improvement EValuation in End-stage Renal Disease[NCT03020303]	Phase 3	2,750 participants (Anticipated)	Interventional	2017-07-07	Recruiting
[NCT01687699]	Phase 4	157 participants (Actual)	Interventional	2008-04-30	Completed
Subjects With Severe Heart Failure and End-Stage Renal Disease on Hemodialysis: A Pilot Study to Assess Safety and Tolerability of Spironolactone[NCT00328809]	Phase 4	0 participants (Actual)	Interventional	2013-06-30	Withdrawn (stopped due to personnel shortage)
Safety and Cardiovascular Efficacy of Spironolactone in Dialysis-Dependent End-Stage Renal Disease (ESRD) (SPin-D) Trial[NCT02285920]	Phase 2	129 participants (Actual)	Interventional	2014-11-30	Completed
Role of Renin Angiotensin Blockade in Peritoneal Fibrosis in Peritoneal Dialysis Patients[NCT00865449]	Phase 3	20 participants (Actual)	Interventional	2008-07-31	Completed
Assessment of the Effects of the Combination of Spironolactone to Conventional Pharmacotherapy in Dialysis Patients[NCT01128101]	Phase 4	60 participants (Anticipated)	Interventional	2011-03-31	Recruiting
Effect of Add-on Spironolactone to Losartan Versus Losartan Alone on Peritoneal Membrane Among Continuous Ambulatory Peritoneal Dialysis Patients: An Open-Label Randomized-Controlled Trial[NCT03953950]	Phase 4	84 participants (Anticipated)	Interventional	2019-10-31	Not yet recruiting
The Effects of Losartan and Spironolactone on Residual Renal Function Preservation in Peritoneal Dialysis Patients[NCT02190318]		96 participants (Anticipated)	Interventional	2013-11-30	Recruiting
ALdosterone Antagonist Chronic HEModialysis Interventional Survival Trial (ALCHEMIST), Phase III b[NCT01848639]	Phase 3	823 participants (Actual)	Interventional	2013-06-30	Completed
Double-blind Placebo-Controlled Randomized Clinical Trial of Mineralocorticoid Receptor Blockade With Eplerenone After Renal Transplantation : Effect on Graft Function at 3 Months.[NCT02490904]	Phase 3	132 participants (Anticipated)	Interventional	2016-10-19	Active, not recruiting
Pilot Trial of Hemodialysis Patient Aldosterone antagoniSm With Eplerenone Trial[NCT01650012]		158 participants (Actual)	Interventional	2013-03-31	Completed
Phase II Trial to Evaluate the Efficacy and Safety of Spironolactone in Hemodialysis Patients[NCT01691053]	Phase 2	118 participants (Actual)	Interventional	2012-12-31	Completed
Barostim Neo® - Baroreflex Activation Therapy® for Heart Failure[NCT02627196]		1,200 participants (Anticipated)	Interventional	2016-04-19	Active, not recruiting
Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist (TOPCAT)[NCT00094302]	Phase 3	3,445 participants (Actual)	Interventional	2006-08-31	Completed
A Phase 4, Randomized, Open Label, Multicenter Prospective Comparative Study To Evaluate The Treatment Of Atrial Fibrillation In Preserved Cardiac Function Heart Failure[NCT04160000]	Phase 4	360 participants (Anticipated)	Interventional	2020-07-26	Recruiting
Randomized Clinical Trial of Radiofrequency Ablation for Atrial Fibrillation in Patients With Heart Failure With Preserved Ejection Fraction for Reduced Healthcare Utilization[NCT04327596]		2 participants (Actual)	Interventional	2021-01-25	Terminated (stopped due to lack of enrollment)
Characterization of Myocardial Interstitial Fibrosis and Cardiomyocyte Hypertrophy by Cardiac MRI In Heart Failure: Implication on Early Remodeling and on the Transition to Heart Failure[NCT03084679]		90 participants (Anticipated)	Interventional	2017-11-01	Recruiting
UK Heart Failure With Preserved Ejection Fraction Registry[NCT05441839]		10,000 participants (Anticipated)	Observational	2022-10-07	Recruiting
Mechanisms and Management of Exercise Intolerance in Older Heart Failure Patients With Preserved Ejection Fraction[NCT03111017]		12 participants (Actual)	Interventional	2017-04-17	Completed
MINeralocorticoid Receptor Antagonist Pretreatment to MINIMISE Reperfusion Injury After ST-Elevation Myocardial Infarction (STEMI)[NCT01882179]	Phase 3	61 participants (Actual)	Interventional	2013-11-30	Completed
Mineralocorticoid Receptor, Coronary Microvascular Function, and Cardiac Efficiency in Hypertension[NCT05593055]	Phase 4	75 participants (Anticipated)	Interventional	2023-08-25	Recruiting
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 Non-interventional, Multicenter, Observational Clinical Trial to Assess Eplerenone Treatment in Patients With Heart Failure.[NCT02344199]		450 participants (Actual)	Observational	2015-03-31	Completed
Efficacy of an m-Health Cardiac Rehabilitation Program in Heart Failure With Preserved Ejection Fraction: A Pilot Randomized Controlled Trial[NCT05002075]		80 participants (Anticipated)	Interventional	2021-11-20	Recruiting
A Prospective Randomized Placebo-controlled Study of the Effect of Eplerenone on Left Ventricular Diastolic Function in Women Receiving Anthracycline Therapy for Breast Cancer[NCT01708798]	Phase 2/Phase 3	44 participants (Actual)	Interventional	2014-05-31	Terminated (stopped due to Futility)
Efficacy and Safety of Treatment With Convalescent Plasma for Adults With COVID-19 Pneumonia. A Double-blinded, Randomized, Multicenter Placebo-controlled Trial[NCT04345289]	Phase 3	147 participants (Actual)	Interventional	2020-05-01	Terminated (stopped due to DSMB advise due to high probability of futility)
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
Usability and Utility Assessment of Passive Remote Monitoring of Multiple Novel Indicators of Heart Failure[NCT04267744]		165 participants (Anticipated)	Interventional	2020-02-11	Active, not recruiting
Pilot Randomized Controlled Trial of Spironolactone in Young Women With Nonalcoholic Steatohepatitis (NASH)[NCT03576755]	Phase 1/Phase 2	20 participants (Actual)	Interventional	2019-01-09	Completed
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

Number of Cardiovascular deaths defined as death due to myocardial infarction, congestive heart failure, cardiac valvular disease, arrhythmia, sudden death, stroke, or peripheral arterial disease (NCT02285920)
Timeframe: 0 - 40 weeks

Safety - Combined Incidence of Potassium >6.5 mEq/L or Serious Hyperkalemia

Intervention	Participants (Count of Participants)
Placebo	1
Spironolactone 12.5 mg	0
Spironolactone 25 mg	2
Spironolactone 50 mg	1

The number of participants who had serum potassium >6.5 mEq/L or serious hyperkalemia was assessed by treatment arm. (NCT02285920)
Timeframe: 0 - 40 Weeks

Safety - Hyperkalemia Requiring Adjustment in Treatment

Intervention	Participants (Count of Participants)
Placebo	13
Spironolactone 12.5 mg	5
Spironolactone 25 mg	5
Spironolactone 50 mg	10

Hyperkalemia requiring adjustment in dialysate potassium concentration, or discontinuation of study medication (NCT02285920)
Timeframe: 0 - 40 weeks

Safety - Number of Participants With Serious Hyperkalemia

Intervention	Participants (Count of Participants)
Placebo	13
Spironolactone 12.5 mg	2
Spironolactone 25 mg	5
Spironolactone 50 mg	7

Number of patients with serious hyperkalemia requiring hospitalization, emergency/unscheduled dialysis or resin therapy (NCT02285920)
Timeframe: 0 - 40 weeks

Safety - Number of Participants With Serum Potassium >6.5 mEq/L

Intervention	Participants (Count of Participants)
Placebo	6
Spironolactone 12.5 mg	2
Spironolactone 25 mg	0
Spironolactone 50 mg	7

The number of participants who had serum potassium >6.5 mEq/L was assessed by treatment arm. (NCT02285920)
Timeframe: 0 - 40 weeks

Safety - Participants With Serious Hypotension

Intervention	Participants (Count of Participants)
Placebo	9
Spironolactone 12.5 mg	4
Spironolactone 25 mg	4
Spironolactone 50 mg	8

The number of participants experiencing serious hypotension, defined as hypotension requiring hospitalization or ED visit and not attributable to overt sepsis, acute myocardial infarction, or other cardiovascular event (e.g. aortic dissection). (NCT02285920)
Timeframe: 0 - 40 weeks

Study Drug Tolerability

Intervention	Participants (Count of Participants)
Placebo	0
Spironolactone 12.5 mg	2
Spironolactone 25 mg	0
Spironolactone 50 mg	3

Tolerability is defined as number of participants who experienced permanent study drug discontinuation or dose reduction. (NCT02285920)
Timeframe: 0 - 36 weeks

Efficacy - Change in Mitral Annular E' Velocity

Intervention	Participants (Count of Participants)
Placebo	16
Spironolactone 12.5 mg	5
Spironolactone 25 mg	6
Spironolactone 50 mg	8

Change in mitral annular E' velocity measured using Tissue Doppler Index (TDI) echocardiography. Efficacy outcomes were considered exploratory with a goal of detecting signals rather than clearly demonstrating efficacy. (NCT02285920)
Timeframe: Baseline to 36 weeks

Efficacy - Secondary Cardiac Outcome Measure - Left Ventricular Ejection Fraction (LVEF)

Intervention	cm/second (Mean)
	Baseline MA E'	36 Week MA E'	Change between baseline - 36 weeks
Placebo	7.4	7.5	0.1
Spironolactone 12.5 mg	7.6	7.4	-0.2
Spironolactone 25 mg	7.8	7.7	-0.1
Spironolactone 50 mg	7.0	7.3	0.3

"Secondary outcome measures include other echocardiographic markers of systolic and diastolic function~• Change in left ventricular ejection fraction between Baseline and 36 weeks" (NCT02285920)
Timeframe: Baseline - 36 weeks

Efficacy - Secondary Cardiac Outcome Measures - Left Ventricular Global Longitudinal Strain (LVGLS)

Intervention	percent ejection fraction (Mean)
	LVEF Baseline	LVEF 36-Week	LVEF Change
Placebo	68.9	70.7	1.8
Spironolactone 12.5 mg	65.9	66.9	1.0
Spironolactone 25 mg	66.0	65.3	-0.7
Spironolactone 50 mg	68.2	69.5	1.3

"Secondary outcome measures include other echocardiographic markers of systolic and diastolic function,~• Change in myocardial strain and strain rate between baseline and 36 weeks" (NCT02285920)
Timeframe: Baseline - 36 weeks

Efficacy - Secondary Cardiac Outcome Measures - Ratio of Mitral Peak Velocity to Diastolic Mitral Annular Velocity (E/E')

Intervention	% of myocardial shortening (Mean)
	LVGLS Baseline	LVGLS 36-week	LVGLS Change
Placebo	-17.2	-18.1	-0.8
Spironolactone 12.5 mg	-16.7	-17.0	-0.3
Spironolactone 25 mg	-17.2	-17.0	0.2
Spironolactone 50 mg	-17.4	-18.2	-0.7

"Secondary outcome measures include other echocardiographic markers of systolic and diastolic function,~• E/E' is the ratio of mitral peak velocity of early filling (E) to early diastolic mitral annular velocity (E')" (NCT02285920)
Timeframe: Baseline - 36 weeks

Efficacy - Secondary Cardiac Outcome Measures Left Ventricular Mass Index (LVMI)

Intervention	ratio (Mean)
	E/E' Baseline	E/E' 36-Week	E/E' Change
Placebo	10.7	11.5	0.9
Spironolactone 12.5 mg	11.8	12.2	0.4
Spironolactone 25 mg	9.2	10.6	1.4
Spironolactone 50 mg	12.5	11.9	-0.6

"Secondary outcome measures include other echocardiographic markers of systolic and diastolic function,~• Change in left ventricular mass index (LVMI) between baseline and 36 weeks" (NCT02285920)
Timeframe: Baseline - 36 weeks

Aborted Cardiac Arrest

Intervention	g/m^2 (Mean)
	LVMI Baseline	LVMI 36-Week	LVMI Change
Placebo	105.2	94.8	-10.4
Spironolactone 12.5 mg	115.5	104.6	-10.9
Spironolactone 25 mg	116.4	109.1	-7.3
Spironolactone 50 mg	106.3	96.5	-9.8

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.

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

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

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)

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)

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)

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)

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

Article	Year
Cardiovascular and kidney outcomes of spironolactone or eplerenone in combination with ACEI/ARBs in patients with diabetic kidney disease. Pharmacotherapy, 2021, Volume: 41, Issue:12 Topics: Adolescent; Adult; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Cardi	2021
Role of eplerenone in the threatment of cardiovascular diseases. Vnitrni lekarstvi, 2023,Spring, Volume: 69, Issue:E-2 Topics: Cardiovascular Diseases; Eplerenone; Heart Failure; Humans; Mineralocorticoid Receptor Antagonists;	2023
Efficacy and safety assessment of mineralocorticoid receptor antagonists in patients with chronic kidney disease. European journal of internal medicine, 2023, Volume: 115 Topics: Bayes Theorem; Cardiovascular Diseases; Creatine; Diabetes Mellitus, Type 2; Diabetic Nephropathies;	2023
The Impact of Spironolactone on Markers of Myocardial Oxidative Status, Inflammation and Remodeling in Hyperthyroid Rats. Current molecular pharmacology, 2020, Volume: 13, Issue:3 Topics: Aldosterone; Animals; Antioxidants; Biomarkers; Blood Pressure; Body Weight; Cardiovascular Diseases	2020
Mineralocorticoid Receptor Antagonists in ESKD. Clinical journal of the American Society of Nephrology : CJASN, 2020, 07-01, Volume: 15, Issue:7 Topics: Aldosterone; Cardiovascular Diseases; Eplerenone; Humans; Kidney Failure, Chronic; Mineralocorticoid	2020
Interaction Between Spironolactone and Natriuretic Peptides in Patients With Heart Failure and Preserved Ejection Fraction: From the TOPCAT Trial. JACC. Heart failure, 2017, Volume: 5, Issue:4 Topics: Aged; Aged, 80 and over; Cardiovascular Diseases; Female; Heart Arrest; Heart Failure; Hospitalizati	2017
Interaction Between Spironolactone and Natriuretic Peptides in Patients With Heart Failure and Preserved Ejection Fraction: From the TOPCAT Trial. JACC. Heart failure, 2017, Volume: 5, Issue:4 Topics: Aged; Aged, 80 and over; Cardiovascular Diseases; Female; Heart Arrest; Heart Failure; Hospitalizati	2017
Interaction Between Spironolactone and Natriuretic Peptides in Patients With Heart Failure and Preserved Ejection Fraction: From the TOPCAT Trial. JACC. Heart failure, 2017, Volume: 5, Issue:4 Topics: Aged; Aged, 80 and over; Cardiovascular Diseases; Female; Heart Arrest; Heart Failure; Hospitalizati	2017
Interaction Between Spironolactone and Natriuretic Peptides in Patients With Heart Failure and Preserved Ejection Fraction: From the TOPCAT Trial. JACC. Heart failure, 2017, Volume: 5, Issue:4 Topics: Aged; Aged, 80 and over; Cardiovascular Diseases; Female; Heart Arrest; Heart Failure; Hospitalizati	2017
Aldosterone antagonist therapy and its relationship with inflammation, fibrosis, thrombosis, mineral-bone disorder and cardiovascular complications in peritoneal dialysis (PD) patients. International urology and nephrology, 2017, Volume: 49, Issue:10 Topics: Adult; Aged; Aged, 80 and over; Aldosterone; Biomarkers; Blood Pressure; Cardiovascular Diseases; Ch	2017
Vascular compliance in women with polycystic ovary syndrome treated with spironolactone. Journal of clinical hypertension (Greenwich, Conn.), 2018, Volume: 20, Issue:10 Topics: Adult; Blood Pressure; Body Mass Index; Cardiovascular Diseases; Elasticity; Female; Glucose Intoler	2018
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
Prognostic implications of plasma volume status estimates in heart failure with preserved ejection fraction: insights from TOPCAT. European journal of heart failure, 2019, Volume: 21, Issue:5 Topics: Aged; Aged, 80 and over; Body Weight; Cardiovascular Diseases; Cause of Death; Female; Heart Failure	2019
Prior Pacemaker Implantation and Clinical Outcomes in Patients With Heart Failure and Preserved Ejection Fraction. JACC. Heart failure, 2019, Volume: 7, Issue:5 Topics: Aged; Aged, 80 and over; Angiotensin II Type 1 Receptor Blockers; Benzimidazoles; Biphenyl Compounds	2019
Effect of spironolactone on cardiovascular complications associated with type-2 diabetes in rats. Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association, 2013, Volume: 121, Issue:8 Topics: Animals; Cardiovascular Diseases; Cytoprotection; Diabetes Mellitus, Experimental; Diabetes Mellitus	2013
Type 2 diabetes-induced cardiovascular complications: comparative evaluation of spironolactone, atenolol, metoprolol, ramipril and perindopril. Clinical and experimental hypertension (New York, N.Y. : 1993), 2014, Volume: 36, Issue:5 Topics: Animals; Animals, Newborn; Antihypertensive Agents; Atenolol; Blood Pressure; Cardiovascular Disease	2014
Mineralocorticoid receptor antagonists in patients with end-stage renal disease on chronic hemodialysis. Journal of the American College of Cardiology, 2014, Feb-18, Volume: 63, Issue:6 Topics: Cardiovascular Diseases; Female; Humans; Kidney Failure, Chronic; Male; Mineralocorticoid Receptor A	2014
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
[Multination clinical trials: what is the relevance and what are the lessons from across-country differences?]. Giornale italiano di cardiologia (2006), 2014, Volume: 15, Issue:4 Topics: Acute Coronary Syndrome; Adenosine; Americas; Benzazepines; Cardiovascular Agents; Cardiovascular Di	2014
Effect of spironolactone in CV mortality in hemodialysis patients. Journal of the American College of Cardiology, 2014, Aug-05, Volume: 64, Issue:5 Topics: Cardiovascular Diseases; Female; Humans; Kidney Failure, Chronic; Male; Mineralocorticoid Receptor A	2014
[Cardiovascular drugs in aged and multimorbid patients]. Praxis, 2015, Sep-16, Volume: 104, Issue:19 Topics: Aged; Aged, 80 and over; Cardiovascular Agents; Cardiovascular Diseases; Combined Modality Therapy;	2015
QRS Duration Is a Predictor of Adverse Outcomes in Heart Failure With Preserved Ejection Fraction. JACC. Heart failure, 2016, Volume: 4, Issue:6 Topics: Aged; Aged, 80 and over; Arrhythmias, Cardiac; Cardiovascular Diseases; Cohort Studies; Electrocardi	2016
The role of aldosterone blockade in end-stage renal disease. Cardiology, 2009, Volume: 114, Issue:1 Topics: Angiotensin-Converting Enzyme Inhibitors; Cardiovascular Diseases; Death, Sudden, Cardiac; Drug Ther	2009
Investigation into the cardiac effects of spironolactone in the experimental model of type 1 diabetes. Journal of cardiovascular pharmacology, 2009, Volume: 54, Issue:6 Topics: Animals; Blood; Blood Glucose; Blood Pressure; Body Weight; Cardiovascular Diseases; Carrier Protein	2009
Aldosterone antagonists--last man standing? The New England journal of medicine, 2011, Jan-06, Volume: 364, Issue:1 Topics: Cardiovascular Diseases; Combined Modality Therapy; Defibrillators, Implantable; Eplerenone; Heart F	2011
Eplerenone in mild heart failure. The New England journal of medicine, 2011, 04-07, Volume: 364, Issue:14 Topics: Aldosterone; Cardiovascular Diseases; Eplerenone; Heart Failure; Humans; Mineralocorticoid Receptor	2011
Eplerenone in mild heart failure. The New England journal of medicine, 2011, 04-07, Volume: 364, Issue:14 Topics: Blood Pressure; Cardiovascular Diseases; Eplerenone; Heart Failure; Humans; Mineralocorticoid Recept	2011
The win ratio: a new approach to the analysis of composite endpoints in clinical trials based on clinical priorities. European heart journal, 2012, Volume: 33, Issue:2 Topics: Angiotensin II Type 1 Receptor Blockers; Aortic Valve Stenosis; Benzimidazoles; Biphenyl Compounds;	2012
[Pharmacological sheet: eplerenone (Inspra), orally]. Journal de pharmacie de Belgique, 2011, Issue:3 Topics: Cardiovascular Diseases; Drug Interactions; Eplerenone; Humans; Mineralocorticoid Receptor Antagonis	2011
Aldosterone is not involved in the ventricular remodeling process induced by tobacco smoke exposure. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology, 2012, Volume: 30, Issue:5 Topics: Aldosterone; Animals; Cardiovascular Diseases; Dietary Supplements; Echocardiography; Male; Rats; Ra	2012
[ALDOSTERONE AND SPIROLACTONES IN THE CLINICAL TREATMENT OF INTERNAL DISEASES (REVIEW OF THE LITERATURE AND ANALYSIS OF PERSONAL CASES)]. Sovetskaia meditsina, 1963, Volume: 27 Topics: Albuminuria; Aldosterone; Blood; Cardiovascular Diseases; Drug Therapy; Humans; Hyperaldosteronism;	1963
Aldosterone and not plasminogen activator inhibitor-1 is a critical mediator of early angiotensin II/NG-nitro-L-arginine methyl ester-induced myocardial injury. Circulation, 2003, Nov-18, Volume: 108, Issue:20 Topics: Aldosterone; Angiotensin II; Animals; Cardiovascular Diseases; Coronary Artery Disease; Disease Mode	2003
The treatment of polycystic ovary syndrome. Minerva ginecologica, 2004, Volume: 56, Issue:1 Topics: Adult; Androgen Antagonists; Cabergoline; Cardiovascular Diseases; Clomiphene; Cyproterone Acetate;	2004
The evolution of aldosterone antagonists. Molecular and cellular endocrinology, 2004, Mar-31, Volume: 217, Issue:1-2 Topics: Aldosterone; Animals; Cardiovascular Diseases; Clinical Trials as Topic; Eplerenone; Gynecomastia; H	2004
The 45-year story of the development of an anti-aldosterone more specific than spironolactone. Molecular and cellular endocrinology, 2004, Mar-31, Volume: 217, Issue:1-2 Topics: Antihypertensive Agents; Cardiovascular Diseases; Chlorthalidone; Clinical Trials as Topic; Erectile	2004
Diagnosis and treatment of polycystic ovarian syndrome and insulin resistance. Pediatric annals, 2005, Volume: 34, Issue:9 Topics: Cardiovascular Diseases; Diabetes Mellitus, Type 2; Female; Humans; Hyperandrogenism; Hyperlipidemia	2005
[41th Congress of EASD (European Association for The Study of Diabetes) 10 to 15 September 2005, Athens, Greece]. La Revue de medecine interne, 2006, Volume: 27, Issue:4 Topics: Aged; Albuminuria; Antihypertensive Agents; Bone Density Conservation Agents; Cardiovascular Disease	2006
Cardiovascular outcomes in patients with primary aldosteronism after treatment. Archives of internal medicine, 2008, Jan-14, Volume: 168, Issue:1 Topics: Adrenalectomy; Adult; Aged; Aldosterone; Cardiovascular Diseases; Female; Follow-Up Studies; Humans;	2008
Cardioprotective therapeutics--drugs used in hypertension, hyperlipidaemia, thromboembolization, arrhythmias, postmenopausal state and as anti-oxidants. Postgraduate medical journal, 1994, Volume: 70, Issue:828 Topics: Angiotensin-Converting Enzyme Inhibitors; Cardiovascular Diseases; Drug Therapy, Combination; Heart	1994
Mineralocorticoid receptor affects AP-1 and nuclear factor-kappab activation in angiotensin II-induced cardiac injury. Hypertension (Dallas, Tex. : 1979), 2001, Volume: 37, Issue:2 Pt 2 Topics: Aldosterone; Angiotensin II; Animals; Animals, Genetically Modified; Blood Pressure; Body Weight; Ca	2001
The endothelin-aldosterone axis and cardiovascular diseases. Journal of cardiovascular pharmacology, 2001, Volume: 38 Suppl 2 Topics: Adrenal Cortex; Aldosterone; Angiotensin-Converting Enzyme Inhibitors; Cardiovascular Diseases; Clin	2001
Effect of treatment of hypertension in the primary preventive trial, Göteborg, Sweden. British journal of clinical pharmacology, 1979, Volume: 7 Suppl 2 Topics: Adrenergic beta-Antagonists; Bethanidine; Cardiovascular Diseases; Cerebrovascular Disorders; Corona	1979
Verapamil and nifedipine in combination for the treatment of hypertrophy heart disease. American journal of hypertension, 1991, Volume: 4, Issue:10 Pt 1 Topics: Adrenal Gland Diseases; Blood Pressure; Cardiovascular Diseases; Drug Therapy, Combination; Humans;	1991
[Clinical significance of long-acting diuretics in the treatment of cardiovascular diseases]. Kokyu to junkan. Respiration & circulation, 1990, Volume: 38, Issue:11 Topics: Acetazolamide; Benzothiadiazines; Cardiovascular Diseases; Delayed-Action Preparations; Diuretics; H	1990
[Severe kaliopenia and electrolytic gradient disturbances in medico-surgical resuscitation. Value of a spironolactone with antialdosterone and catatoxic effect]. Agressologie: revue internationale de physio-biologie et de pharmacologie appliquees aux effets de l'agression, 1971, Volume: 12, Issue:3 Topics: Brain Edema; Cardiac Surgical Procedures; Cardiovascular Diseases; Extracorporeal Circulation; Human	1971
[Steroids and nephrectomy cardiopathy]. Revue canadienne de biologie, 1970, Volume: 29, Issue:2 Topics: Animals; Calcinosis; Cardiovascular Diseases; Desoxycorticosterone; Estradiol; Ethylestrenol; Heart	1970
Newer diuretics in the treatment of cardiac or hepatic disease in elderly patients. Journal of the American Geriatrics Society, 1966, Volume: 14, Issue:12 Topics: Ascites; Benzothiadiazines; Blood Glucose; Blood Urea Nitrogen; Body Weight; Cardiovascular Diseases	1966

spironolactone and Cardiovascular Diseases

Research Excerpts

Research

Studies (98)

Authors

Clinical Trials (33)

Trial Overview

Trial Outcomes

Safety - Cardiovascular Death

Safety - Combined Incidence of Potassium >6.5 mEq/L or Serious Hyperkalemia

Safety - Hyperkalemia Requiring Adjustment in Treatment

Safety - Number of Participants With Serious Hyperkalemia

Safety - Number of Participants With Serum Potassium >6.5 mEq/L

Safety - Participants With Serious Hypotension

Study Drug Tolerability

Efficacy - Change in Mitral Annular E' Velocity

Efficacy - Secondary Cardiac Outcome Measure - Left Ventricular Ejection Fraction (LVEF)

Efficacy - Secondary Cardiac Outcome Measures - Left Ventricular Global Longitudinal Strain (LVGLS)

Efficacy - Secondary Cardiac Outcome Measures - Ratio of Mitral Peak Velocity to Diastolic Mitral Annular Velocity (E/E')

Efficacy - Secondary Cardiac Outcome Measures Left Ventricular Mass Index (LVMI)

Aborted Cardiac Arrest

All-cause Mortality

Cardiovascular Mortality

Cardiovascular-related Hospitalization

Chloride

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

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

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

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

Depression Symptoms, as Measured by Patient Health Questionnaire.

Deterioration of Renal Function

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

Estimated Glomerular Filtration Rate (GFR)

Hospitalization for Any Reason

Hospitalization for the Management of Heart Failure

Myocardial Infarction

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

Potassium

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

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

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

Serum Creatinine

Sodium

Stroke

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Number of Participants With New Onset Atrial Fibrillation or Flutter

Number of Participants With New Onset Diabetes Mellitus (DM)

Reviews

Trials

Other Studies