spironolactone and Hypertrophy, Left Ventricular 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.

Hypertrophy, Left Ventricular: Enlargement of the LEFT VENTRICLE of the heart. This increase in ventricular mass is attributed to sustained abnormal pressure or volume loads and is a contributor to cardiovascular morbidity and mortality.

Research Excerpts

Excerpt	Relevance	Reference
"The mineralocorticoid receptor antagonist spironolactone has been shown to improve cardiac function and reverse left ventricular hypertrophy in heart failure patients, but there are no consistent findings on the efficacy and safety in hemodialysis patients."	9.41	Research Progress on the Efficacy and Safety of Spironolactone in Reversing Left Ventricular Hypertrophy in Hemodialysis Patients. ( Chen, Z; Li, Z; Liu, R; Lu, G; Sun, Y; Sun, Z, 2023)
" In nondialytic chronic kidney disease, spironolactone was safe and effective in reducing left ventricular hypertrophy."	9.20	Spironolactone is secure and reduces left ventricular hypertrophy in hemodialysis patients. ( Barretti, P; Caramori, JC; Castro, AD; De Stefano, LM; Feniman-De-Stefano, GM; Franco, RJ; Martin, LC; Xavier, PS; Zanati-Basan, SG, 2015)
"5 mg hydrochorothiazide + 5 mg amlodipine, 86 patients with resistant hypertension were randomized to the add-on 25 mg spironolactone (MRB group, n = 46) or 5 mg ramipril (RASB group, n = 40) groups for 12 weeks."	9.19	Greater efficacy of aldosterone blockade and diuretic reinforcement vs. dual renin-angiotensin blockade for left ventricular mass regression in patients with resistant hypertension. ( Azizi, M; Bobrie, G; Chatellier, G; Frank, M; Ménard, J; Perdrix, L; Plouin, PF, 2014)
" Further, this is the first study demonstrating amiloride could also improve myocardial fibrosis."	9.17	Myocardial fibrosis and QTc are reduced following treatment with spironolactone or amiloride in stroke survivors: a randomised placebo-controlled cross-over trial. ( MacWalter, RS; McSwiggan, S; Ogston, SA; Struthers, AD; Sze, KY; Wong, KY; Wong, SY, 2013)
" Spironolactone is thought to be an important addition to resistant hypertension (RH) treatment."	9.14	Aldosterone excess or escape: Treating resistant hypertension. ( Adriana de Souza, L; Coca, A; Coelho, OR; Ferreira-Melo, S; Martins, LC; Moreno, H; Pimenta, E; Sierra, C; Ubaid-Girioli, S; Yugar-Toledo, JC, 2009)
"The aim of the study is to determine whether the selective aldosterone-receptor antagonist eplerenone delays onset of left ventricular (LV) systolic dysfunction or reduces LV hypertrophy in asymptomatic patients with moderate to severe aortic stenosis."	9.13	A randomized trial of the aldosterone-receptor antagonist eplerenone in asymptomatic moderate-severe aortic stenosis. ( Cowan, BR; Doughty, RN; Edwards, C; Freidlander, D; Kerr, AJ; Occleshaw, C; Richards, AM; Stewart, RA; Whalley, GA; White, HD; Williams, M; Young, AA; Zeng, I, 2008)
"The patients with essential hypertension were randomly divided into 2 groups; 1 group was treated with an ARB, candesartan (8 mg/day), for 1 year (ARB group) and other group was treated with the ARB for the first 6 months and with the ARB plus SPRL (25 mg/day) for the next 6 months (combination group)."	9.12	Effects of spironolactone during an angiotensin II receptor blocker treatment on the left ventricular mass reduction in hypertensive patients with concentric left ventricular hypertrophy. ( Date, T; Kawai, M; Mochizuki, S; Seki, S; Shimizu, M; Taniguchi, I; Taniguchi, M; Yoshida, S, 2006)
"A 9-month, double-blind, randomized study was performed in 202 patients with LVH and hypertension who received eplerenone 200 mg daily, enalapril 40 mg daily, or eplerenone 200 mg and enalapril 10 mg daily."	9.10	Effects of eplerenone, enalapril, and eplerenone/enalapril in patients with essential hypertension and left ventricular hypertrophy: the 4E-left ventricular hypertrophy study. ( Burns, D; Kleiman, J; Krause, S; Phillips, RA; Pitt, B; Reichek, N; Roniker, B; Willenbrock, R; Williams, GH; Zannad, F, 2003)
"It has been reported that treatment with an angiotensin-converting enzyme (ACE) inhibitor is not adequate to suppress aldosterone, and we previously demonstrated that adding spironolactone to an ACE inhibitor may have beneficial effects on left ventricular hypertrophy (LVH) in selected patients with essential hypertension (EH)."	9.10	Relative long-term effects of spironolactone in conjunction with an angiotensin-converting enzyme inhibitor on left ventricular mass and diastolic function in patients with essential hypertension. ( Hayashi, M; Saruta, T; Sato, A, 2002)
"We recently demonstrated that spironolactone may have beneficial effects on left ventricular hypertrophy in selected patients with essential hypertension undergoing treatment with an angiotensin-converting enzyme (ACE) inhibitor."	9.09	High serum level of procollagen type III amino-terminal peptide contributes to the efficacy of spironolactone and angiotensin-converting enzyme inhibitor therapy on left ventricular hypertrophy in essential hypertensive patients. ( Saruta, T; Sato, A; Takane, H, 2001)
" In the present study, we examined the effect on left ventricular hypertrophy of adding a low dose of the mineralocorticoid receptor antagonist spironolactone (25 mg/d) to an angiotensin-converting enzyme inhibitor (enalapril maleate) in patients with essential hypertension."	9.09	Effects of spironolactone and angiotensin-converting enzyme inhibitor on left ventricular hypertrophy in patients with essential hypertension. ( Saruta, T; Sato, A; Suzuki, Y, 1999)
" Patients with mild to moderate essential hypertension were treated with spironolactone/altizide for two months and were included in the study if their blood pressure (BP) at the end of this first treatment period was normalised according to protocol criteria (systolic BP < 160 mm Hg and diastolic BP < 95 mm Hg)."	9.08	Effects of spironolactone-altizide on left ventricular hypertrophy. ( Brohet, C; Cosyns, J; Degre, S; Detry, JM; Kormoss, N; Unger, P, 1998)
"Patients hospitalized for a first episode of acute myocardial infarction were blindly and randomly assigned to receive ramipril (2."	9.08	[Effects of ramipril and spironolactone on ventricular remodeling after acute myocardial infarction: randomized and double-blind study]. ( Castro, P; Chávez, A; Chávez, E; Corbalán, R; Godoy, I; Quintana, JC; Rodríguez, JA; Yovanovich, J, 1997)
"We have previously shown rapid reversal of left ventricular hypertrophy (LVH) with 6 months of spironolactone therapy in patients with resistant hypertension (HTN), preserved left ventricular ejection fraction and no history of heart failure."	7.81	Effect of spironolactone on diastolic function in hypertensive left ventricular hypertrophy. ( Aban, I; Calhoun, DA; Dell'Italia, LJ; Denney, TS; Gaddam, KK; Gupta, A; Gupta, H; Lloyd, SG; Oparil, S; Schiros, CG, 2015)
"Dogs subjected to RVP for 8 weeks in the absence or presence of eplerenone treatment during the final 4 weeks of pacing were assessed by echocardiography, electrophysiology study,ventricular fibrosis measurements, and inflammatory cytokine mRNA expression analysis."	7.80	Eplerenone-mediated regression of electrical activation delays and myocardial fibrosis in heart failure. ( , 2014)
"Two-month-old SHHF rats were randomized to receive no treatment (SHHF group), a standard heart failure therapy (quinapril-torasemide-carvedilol; ST-SHHF group), or the combination of eplerenone and standard heart failure therapy (Eple+ST-SHHF group) for 20 months."	7.79	Eplerenone enhances cardioprotective effects of standard heart failure therapy through matricellular proteins in hypertensive heart failure. ( Aragoncillo, P; Caro-Vadillo, A; Casanueva-Eliceiry, S; Egido, J; Fernández-Cruz, A; Gómez-Garre, D; Muñoz-Pacheco, P; Ortega-Hernández, A, 2013)
"The aim of the present study was to evaluate the effect of low-dose spironolactone initiated during the early stages of hypertension development and to assess the effects of chronic pressure overload on ventricular remodeling in rats."	7.77	Long-term use of low-dose spironolactone in spontaneously hypertensive rats: effects on left ventricular hypertrophy and stiffness. ( Baldo, MP; Forechi, L; Lunz, W; Machado, RC; Mill, JG; Morra, EA; Rodrigues, SL; Zaniqueli, D, 2011)
" Blood pressure, heart rate, concentrations of aldosterone, urea, creatinine, electrolytes, and protein, index of hypertrophy of visceral organs, and 24-h diuresis were evaluated."	7.74	Effect of spironolactone on hypertrophy of left ventricular myocardium in wistar rats with experimental uremia. ( Beresneva, ON; Esaian, AM; Karabayeva, AZh; Kayukov, IG; Kotenko, LV; Parastaeva, MM; Sevastyanova, IE, 2008)
"We investigated, whether the substrate for nitric oxide (NO) formation -L-arginine - and the aldosterone receptor antagonist - spironolactone - are able to reverse alterations of the left ventricle (LV) and aorta in N(omega)-nitro-L-arginine methyl ester (L-NAME)-induced hypertension."	7.74	Regression of left ventricular hypertrophy and aortic remodelling in NO-deficient hypertensive rats: effect of L-arginine and spironolactone. ( Adamcova, M; Hulin, I; Janega, P; Krajcirovicova, K; Matuskova, J; Paulis, L; Pechanova, O; Pelouch, V; Potacova, A; Simko, F; Simko, J, 2008)
"Aldosterone receptor antagonist, spironolactone, has been shown to prevent remodeling of the heart in several models of left ventricular hypertrophy."	7.74	Spironolactone differently influences remodeling of the left ventricle and aorta in L-NAME-induced hypertension. ( Krajcírovicová, K; Lupták, I; Matúsková, J; Paulis, L; Pechánová, O; Pelouch, V; Pincíková, T; Pomsár, J; Simko, F; Stvrtina, S, 2007)
"N(G)-nitro-L-arginine-methyl ester (L-NAME)-induced hypertension is associated with protein remodeling of the left ventricle."	7.74	Spontaneous, L-arginine-induced and spironolactone-induced regression of protein remodeling of the left ventricle in L-NAME-induced hypertension. ( Adamcová, M; Krajcírovicová, K; Matúsková, J; Paulis, L; Pechánová, O; Pelouch, V; Potácová, A; Simko, F, 2007)
"The frequency of left ventricular hypertrophy (LVH) dropped by 10% (χ²=3."	6.94	EFFICACY OF SPIRONOLACTONE IN ANTIHYPERTENSIVE THERAPY IN PATIENTS WITH RESISTANT HYPERTENSION IN COMBINATION WITH RHEUMATOID ARTHRITIS. ( Hai, O; Karmazin, Y; Karmazina, O; Kondratiuk, V; Stakhova, A, 2020)
"Primary aldosteronism (PA) represents the most common cause of secondary hypertension."	6.80	Long-term effects of adrenalectomy or spironolactone on blood pressure control and regression of left ventricle hypertrophy in patients with primary aldosteronism. ( Holaj, R; Indra, T; Petrák, O; Rosa, J; Šomlóová, Z; Štrauch, B; Widimský, J, 2015)
"The mineralocorticoid receptor antagonist spironolactone has been shown to improve cardiac function and reverse left ventricular hypertrophy in heart failure patients, but there are no consistent findings on the efficacy and safety in hemodialysis patients."	5.41	Research Progress on the Efficacy and Safety of Spironolactone in Reversing Left Ventricular Hypertrophy in Hemodialysis Patients. ( Chen, Z; Li, Z; Liu, R; Lu, G; Sun, Y; Sun, Z, 2023)
"The incidence of left ventricular hypertrophy (LVH) in primary aldosteronism (PA) is higher than in essential hypertension."	5.39	Regression of left ventricular hypertrophy in patients with primary aldosteronism/low-renin hypertension on low-dose spironolactone. ( Bergman, M; Chagnac, A; Gafter, U; Herman-Edelstein, M; Korzets, A; Ori, Y; Salman, H; Zingerman, B, 2013)
"Losartan treatment decreased systolic pressure and yellow-red collagen fiber content in all areas, whereas spironolactone treatment decreased green collagen fiber content without decreasing systolic pressure."	5.29	Left ventricular fibrosis in renovascular hypertensive rats. Effect of losartan and spironolactone. ( Appay, MD; Bariety, J; Heudes, D; Hinglais, N; Michel, JB; Nicoletti, A; Philippe, M; Sassy-Prigent, C, 1995)
" In nondialytic chronic kidney disease, spironolactone was safe and effective in reducing left ventricular hypertrophy."	5.20	Spironolactone is secure and reduces left ventricular hypertrophy in hemodialysis patients. ( Barretti, P; Caramori, JC; Castro, AD; De Stefano, LM; Feniman-De-Stefano, GM; Franco, RJ; Martin, LC; Xavier, PS; Zanati-Basan, SG, 2015)
"5 mg hydrochorothiazide + 5 mg amlodipine, 86 patients with resistant hypertension were randomized to the add-on 25 mg spironolactone (MRB group, n = 46) or 5 mg ramipril (RASB group, n = 40) groups for 12 weeks."	5.19	Greater efficacy of aldosterone blockade and diuretic reinforcement vs. dual renin-angiotensin blockade for left ventricular mass regression in patients with resistant hypertension. ( Azizi, M; Bobrie, G; Chatellier, G; Frank, M; Ménard, J; Perdrix, L; Plouin, PF, 2014)
" Further, this is the first study demonstrating amiloride could also improve myocardial fibrosis."	5.17	Myocardial fibrosis and QTc are reduced following treatment with spironolactone or amiloride in stroke survivors: a randomised placebo-controlled cross-over trial. ( MacWalter, RS; McSwiggan, S; Ogston, SA; Struthers, AD; Sze, KY; Wong, KY; Wong, SY, 2013)
"The purpose of this study was to identify the effects of spironolactone on left ventricular (LV) structure and function, and serological fibrosis markers in patients with metabolic syndrome (MS) taking angiotensin-converting enzyme inhibitors or angiotensin receptor blockers."	5.15	A randomized study of the beneficial effects of aldosterone antagonism on LV function, structure, and fibrosis markers in metabolic syndrome. ( Kosmala, W; Marwick, TH; Mysiak, A; O'Moore-Sullivan, T; Przewlocka-Kosmala, M; Szczepanik-Osadnik, H, 2011)
" Spironolactone is thought to be an important addition to resistant hypertension (RH) treatment."	5.14	Aldosterone excess or escape: Treating resistant hypertension. ( Adriana de Souza, L; Coca, A; Coelho, OR; Ferreira-Melo, S; Martins, LC; Moreno, H; Pimenta, E; Sierra, C; Ubaid-Girioli, S; Yugar-Toledo, JC, 2009)
"The aim of the study is to determine whether the selective aldosterone-receptor antagonist eplerenone delays onset of left ventricular (LV) systolic dysfunction or reduces LV hypertrophy in asymptomatic patients with moderate to severe aortic stenosis."	5.13	A randomized trial of the aldosterone-receptor antagonist eplerenone in asymptomatic moderate-severe aortic stenosis. ( Cowan, BR; Doughty, RN; Edwards, C; Freidlander, D; Kerr, AJ; Occleshaw, C; Richards, AM; Stewart, RA; Whalley, GA; White, HD; Williams, M; Young, AA; Zeng, I, 2008)
"The patients with essential hypertension were randomly divided into 2 groups; 1 group was treated with an ARB, candesartan (8 mg/day), for 1 year (ARB group) and other group was treated with the ARB for the first 6 months and with the ARB plus SPRL (25 mg/day) for the next 6 months (combination group)."	5.12	Effects of spironolactone during an angiotensin II receptor blocker treatment on the left ventricular mass reduction in hypertensive patients with concentric left ventricular hypertrophy. ( Date, T; Kawai, M; Mochizuki, S; Seki, S; Shimizu, M; Taniguchi, I; Taniguchi, M; Yoshida, S, 2006)
"A 9-month, double-blind, randomized study was performed in 202 patients with LVH and hypertension who received eplerenone 200 mg daily, enalapril 40 mg daily, or eplerenone 200 mg and enalapril 10 mg daily."	5.10	Effects of eplerenone, enalapril, and eplerenone/enalapril in patients with essential hypertension and left ventricular hypertrophy: the 4E-left ventricular hypertrophy study. ( Burns, D; Kleiman, J; Krause, S; Phillips, RA; Pitt, B; Reichek, N; Roniker, B; Willenbrock, R; Williams, GH; Zannad, F, 2003)
"It has been reported that treatment with an angiotensin-converting enzyme (ACE) inhibitor is not adequate to suppress aldosterone, and we previously demonstrated that adding spironolactone to an ACE inhibitor may have beneficial effects on left ventricular hypertrophy (LVH) in selected patients with essential hypertension (EH)."	5.10	Relative long-term effects of spironolactone in conjunction with an angiotensin-converting enzyme inhibitor on left ventricular mass and diastolic function in patients with essential hypertension. ( Hayashi, M; Saruta, T; Sato, A, 2002)
" In the present study, we examined the effect on left ventricular hypertrophy of adding a low dose of the mineralocorticoid receptor antagonist spironolactone (25 mg/d) to an angiotensin-converting enzyme inhibitor (enalapril maleate) in patients with essential hypertension."	5.09	Effects of spironolactone and angiotensin-converting enzyme inhibitor on left ventricular hypertrophy in patients with essential hypertension. ( Saruta, T; Sato, A; Suzuki, Y, 1999)
"We recently demonstrated that spironolactone may have beneficial effects on left ventricular hypertrophy in selected patients with essential hypertension undergoing treatment with an angiotensin-converting enzyme (ACE) inhibitor."	5.09	High serum level of procollagen type III amino-terminal peptide contributes to the efficacy of spironolactone and angiotensin-converting enzyme inhibitor therapy on left ventricular hypertrophy in essential hypertensive patients. ( Saruta, T; Sato, A; Takane, H, 2001)
"Patients hospitalized for a first episode of acute myocardial infarction were blindly and randomly assigned to receive ramipril (2."	5.08	[Effects of ramipril and spironolactone on ventricular remodeling after acute myocardial infarction: randomized and double-blind study]. ( Castro, P; Chávez, A; Chávez, E; Corbalán, R; Godoy, I; Quintana, JC; Rodríguez, JA; Yovanovich, J, 1997)
" Patients with mild to moderate essential hypertension were treated with spironolactone/altizide for two months and were included in the study if their blood pressure (BP) at the end of this first treatment period was normalised according to protocol criteria (systolic BP < 160 mm Hg and diastolic BP < 95 mm Hg)."	5.08	Effects of spironolactone-altizide on left ventricular hypertrophy. ( Brohet, C; Cosyns, J; Degre, S; Detry, JM; Kormoss, N; Unger, P, 1998)
"Either alone or in combination with other antihypertensive agents, eplerenone appears to be effective for the treatment of hypertension."	4.82	The cardiovascular effects of eplerenone, a selective aldosterone-receptor antagonist. ( Davis, KL; Nappi, JM, 2003)
" Spironolactone and eplerenone are the mineralocorticoid receptor (MR) antagonists currently available for the treatment of hypertension."	4.82	Mineralocorticoid receptor antagonists and hypertension: is there a rationale? ( Gumieniak, O; Williams, GH, 2004)
" Due to the potential importance of these mechanisms, the finding that there is a significant correlation between aldosterone production and mortality in patients with heart failure, as well as evidence that an aldosterone antagonist, spironolactone, when administered to patients with heart failure treated with conventional therapy including an ACE inhibitor results in increased diuresis and symptomatic improvement, an international prospective multicenter study has been organized, the Randomized Aldactone Evaluation Study (RALES Pilot Study), to evaluate the safety of blocking the effects of aldosterone in patients with heart failure treated with an ACE inhibitor."	4.79	"Escape" of aldosterone production in patients with left ventricular dysfunction treated with an angiotensin converting enzyme inhibitor: implications for therapy. ( Pitt, B, 1995)
"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)
"We have previously shown rapid reversal of left ventricular hypertrophy (LVH) with 6 months of spironolactone therapy in patients with resistant hypertension (HTN), preserved left ventricular ejection fraction and no history of heart failure."	3.81	Effect of spironolactone on diastolic function in hypertensive left ventricular hypertrophy. ( Aban, I; Calhoun, DA; Dell'Italia, LJ; Denney, TS; Gaddam, KK; Gupta, A; Gupta, H; Lloyd, SG; Oparil, S; Schiros, CG, 2015)
"Dogs subjected to RVP for 8 weeks in the absence or presence of eplerenone treatment during the final 4 weeks of pacing were assessed by echocardiography, electrophysiology study,ventricular fibrosis measurements, and inflammatory cytokine mRNA expression analysis."	3.80	Eplerenone-mediated regression of electrical activation delays and myocardial fibrosis in heart failure. ( , 2014)
"Two-month-old SHHF rats were randomized to receive no treatment (SHHF group), a standard heart failure therapy (quinapril-torasemide-carvedilol; ST-SHHF group), or the combination of eplerenone and standard heart failure therapy (Eple+ST-SHHF group) for 20 months."	3.79	Eplerenone enhances cardioprotective effects of standard heart failure therapy through matricellular proteins in hypertensive heart failure. ( Aragoncillo, P; Caro-Vadillo, A; Casanueva-Eliceiry, S; Egido, J; Fernández-Cruz, A; Gómez-Garre, D; Muñoz-Pacheco, P; Ortega-Hernández, A, 2013)
"Spironolactone reduces left ventricular hypertrophy secondary to high salt intake and ventricular stiffness in adult SHRs."	3.77	Effects of spironolactone in spontaneously hypertensive adult rats subjected to high salt intake. ( Baldo, MP; Forechi, L; Machado, RC; Mill, JG; Rodrigues, SL; Zaniqueli, D, 2011)
"The aim of the present study was to evaluate the effect of low-dose spironolactone initiated during the early stages of hypertension development and to assess the effects of chronic pressure overload on ventricular remodeling in rats."	3.77	Long-term use of low-dose spironolactone in spontaneously hypertensive rats: effects on left ventricular hypertrophy and stiffness. ( Baldo, MP; Forechi, L; Lunz, W; Machado, RC; Mill, JG; Morra, EA; Rodrigues, SL; Zaniqueli, D, 2011)
"We investigated, whether the substrate for nitric oxide (NO) formation -L-arginine - and the aldosterone receptor antagonist - spironolactone - are able to reverse alterations of the left ventricle (LV) and aorta in N(omega)-nitro-L-arginine methyl ester (L-NAME)-induced hypertension."	3.74	Regression of left ventricular hypertrophy and aortic remodelling in NO-deficient hypertensive rats: effect of L-arginine and spironolactone. ( Adamcova, M; Hulin, I; Janega, P; Krajcirovicova, K; Matuskova, J; Paulis, L; Pechanova, O; Pelouch, V; Potacova, A; Simko, F; Simko, J, 2008)
"N(G)-nitro-L-arginine-methyl ester (L-NAME)-induced hypertension is associated with protein remodeling of the left ventricle."	3.74	Spontaneous, L-arginine-induced and spironolactone-induced regression of protein remodeling of the left ventricle in L-NAME-induced hypertension. ( Adamcová, M; Krajcírovicová, K; Matúsková, J; Paulis, L; Pechánová, O; Pelouch, V; Potácová, A; Simko, F, 2007)
"Aldosterone receptor antagonist, spironolactone, has been shown to prevent remodeling of the heart in several models of left ventricular hypertrophy."	3.74	Spironolactone differently influences remodeling of the left ventricle and aorta in L-NAME-induced hypertension. ( Krajcírovicová, K; Lupták, I; Matúsková, J; Paulis, L; Pechánová, O; Pelouch, V; Pincíková, T; Pomsár, J; Simko, F; Stvrtina, S, 2007)
" Blood pressure, heart rate, concentrations of aldosterone, urea, creatinine, electrolytes, and protein, index of hypertrophy of visceral organs, and 24-h diuresis were evaluated."	3.74	Effect of spironolactone on hypertrophy of left ventricular myocardium in wistar rats with experimental uremia. ( Beresneva, ON; Esaian, AM; Karabayeva, AZh; Kayukov, IG; Kotenko, LV; Parastaeva, MM; Sevastyanova, IE, 2008)
" To these we now add anti-aldosterone strategies with the phenomenal success of spironolactone in reducing mortality in severe heart failure."	3.71	Exciting new drugs on the horizon - eplerenone, a selective aldosterone receptor antagonist (SARA). ( Coats, AJ, 2001)
"The frequency of left ventricular hypertrophy (LVH) dropped by 10% (χ²=3."	2.94	EFFICACY OF SPIRONOLACTONE IN ANTIHYPERTENSIVE THERAPY IN PATIENTS WITH RESISTANT HYPERTENSION IN COMBINATION WITH RHEUMATOID ARTHRITIS. ( Hai, O; Karmazin, Y; Karmazina, O; Kondratiuk, V; Stakhova, A, 2020)
"Primary aldosteronism (PA) represents the most common cause of secondary hypertension."	2.80	Long-term effects of adrenalectomy or spironolactone on blood pressure control and regression of left ventricle hypertrophy in patients with primary aldosteronism. ( Holaj, R; Indra, T; Petrák, O; Rosa, J; Šomlóová, Z; Štrauch, B; Widimský, J, 2015)
"Spironolactone treatment (19 patients in the high aldosterone group and 15 patients from the normal aldosterone group participated in the follow-up) resulted in a significant decrease in clinic systolic blood pressure, right and left ventricular end diastolic volumes, left atrial volume, left ventricular mass, and brain natriuretic peptide at 3 and 6 months of follow-up in patients with high aldosterone, whereas in those with normal aldosterone status, spironolactone decreased blood pressure and left ventricular mass without changes in ventricular or atrial volumes or plasma brain natriuretic peptide."	2.75	Rapid reversal of left ventricular hypertrophy and intracardiac volume overload in patients with resistant hypertension and hyperaldosteronism: a prospective clinical study. ( Aban, I; Ahmed, M; Calhoun, DA; Corros, C; Dell'Italia, LJ; Denney, T; Gaddam, K; Gupta, H; Husain, A; Inusah, S; Lloyd, SG; Oparil, S; Pimenta, E, 2010)
"Obesity has been shown to be associated with increased left ventricular mass (LVM) and heart sympathetic activity even in nonhypertensive subjects."	2.71	Effect of losartan and spironolactone on left ventricular mass and heart sympathetic activity in prehypertensive obese subjects: a 16-week randomized trial. ( Amador, N; Encarnación, JJ; Guízar, JM; López, M; Rodríguez, L, 2005)
"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)
"Eplerenone has already been approved for the treatment of systemic hypertension and has been evaluated in numerous hypertension subgroups, including patients with low plasma renin activity; diabetes; LVH; uncontrolled blood pressure while receiving monotherapy with angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, calcium channel blockers, or beta-blockers; and in black patients."	2.42	Eplerenone: a selective aldosterone blocker. ( Stier, CT, 2003)
"Hypertension results in left ventricular hypertrophy and cardiac dysfunction."	1.51	Myocardial global longitudinal strain: An early indicator of cardiac interstitial fibrosis modified by spironolactone, in a unique hypertensive rat model. ( Coffey, S; Leader, CJ; Moharram, M; Sammut, IA; Walker, RJ; Wilkins, GW, 2019)
"Primary aldosteronism is associated with increased left ventricular (LV) mass independently of blood pressure."	1.43	Dietary Salt Intake Is a Determinant of Cardiac Changes After Treatment of Primary Aldosteronism: A Prospective Study. ( Bertin, N; Catena, C; Colussi, G; Novello, M; Pilz, S; Sechi, LA; Tomaschitz, A; Verheyen, ND, 2016)
"The incidence of left ventricular hypertrophy (LVH) in primary aldosteronism (PA) is higher than in essential hypertension."	1.39	Regression of left ventricular hypertrophy in patients with primary aldosteronism/low-renin hypertension on low-dose spironolactone. ( Bergman, M; Chagnac, A; Gafter, U; Herman-Edelstein, M; Korzets, A; Ori, Y; Salman, H; Zingerman, B, 2013)
"Spironolactone treatment reversed all the above effects."	1.37	A role for cardiotrophin-1 in myocardial remodeling induced by aldosterone. ( Cachofeiro, V; Díez, J; Fortuno, MA; Lahera, V; López-Andrés, N; Martin-Fernandez, B; Rossignol, P; Zannad, F, 2011)
"Melatonin was shown to reduce blood pressure, oxidative load and to increase nitric oxide bioavailability predisposing melatonin to have antiremodelling potential."	1.35	Effect of melatonin, captopril, spironolactone and simvastatin on blood pressure and left ventricular remodelling in spontaneously hypertensive rats. ( Adamcova, M; Bednarova, K; Krajcirovicova, K; Mullerova, M; Paulis, L; Pechanova, O; Pelouch, V; Simko, F, 2009)
"The association between low blood pressure (BP) levels and increased mortality has been established in several studies of heart failure (HF)."	1.35	Association of blood pressure and its evolving changes with the survival of patients with heart failure. ( Almendral, J; Bardaji, A; Bayes-Genis, A; Cinca, J; de Luna, AB; Fernandez-Palomeque, C; Gonzalez-JuAnatey, JR; Grigorian-Shamagian, L; Jimenez, RP; Macaya, C; Nieto, V; Pascual, D; Vazquez, R, 2008)
"Fifty-four patients with primary aldosteronism were enrolled in a prospective study and were followed for a mean of 6."	1.34	Long-term cardiac effects of adrenalectomy or mineralocorticoid antagonists in patients with primary aldosteronism. ( Catena, C; Chiuch, A; Colussi, G; Gianfagna, P; Lapenna, R; Nadalini, E; Sechi, LA, 2007)
"Losartan treatment decreased systolic pressure and yellow-red collagen fiber content in all areas, whereas spironolactone treatment decreased green collagen fiber content without decreasing systolic pressure."	1.29	Left ventricular fibrosis in renovascular hypertensive rats. Effect of losartan and spironolactone. ( Appay, MD; Bariety, J; Heudes, D; Hinglais, N; Michel, JB; Nicoletti, A; Philippe, M; Sassy-Prigent, C, 1995)

Research

Studies (69)

Authors

Clinical Trials (8)

Trial Overview

Trial Outcomes

Aborted Cardiac Arrest

Timeframe	Studies, this research(%)	All Research%
pre-1990	0 (0.00)	18.7374
1990's	5 (7.25)	18.2507
2000's	33 (47.83)	29.6817
2010's	27 (39.13)	24.3611
2020's	4 (5.80)	2.80

Authors	Studies
Ageev, FT	1
Ovchinnikov, AG	1
Sun, Z	1
Chen, Z	1
Liu, R	1
Lu, G	1
Li, Z	1
Sun, Y	1
Mandal, C	1
Dutta, PK	1
Leader, CJ	1
Moharram, M	1
Coffey, S	1
Sammut, IA	1
Wilkins, GW	1
Walker, RJ	1
Kondratiuk, V	1
Stakhova, A	1
Hai, O	1
Karmazina, O	1
Karmazin, Y	1
Hayer, MK	1
Edwards, NC	2
Slinn, G	1
Moody, WE	1
Steeds, RP	2
Ferro, CJ	2
Price, AM	1
Andujar, C	1
Dutton, M	1
Webster, R	1
Webb, DJ	1
Semple, S	1
MacIntyre, I	1
Melville, V	1
Wilkinson, IB	1
Hiemstra, TF	1
Wheeler, DC	1
Herrey, A	1
Grant, M	1
Mehta, S	1
Ives, N	1
Townend, JN	2
Funder, JW	1
Wong, KY	1
Wong, SY	1
McSwiggan, S	1
Ogston, SA	1
Sze, KY	1
MacWalter, RS	1
Struthers, AD	1
Muñoz-Pacheco, P	1
Ortega-Hernández, A	1
Caro-Vadillo, A	1
Casanueva-Eliceiry, S	1
Aragoncillo, P	1
Egido, J	1
Fernández-Cruz, A	1
Gómez-Garre, D	1
Shah, AM	1
Shah, SJ	1
Anand, IS	1
Sweitzer, NK	1
O'Meara, E	1
Heitner, JF	1
Sopko, G	1
Li, G	1
Assmann, SF	1
McKinlay, SM	1
Pitt, B	5
Pfeffer, MA	1
Solomon, SD	1
Ito, Y	1
Mizuno, M	1
Suzuki, Y	2
Tamai, H	1
Hiramatsu, T	1
Ohashi, H	1
Ito, I	1
Kasuga, H	1
Horie, M	1
Maruyama, S	1
Yuzawa, Y	1
Matsubara, T	1
Matsuo, S	1
Azizi, M	1
Perdrix, L	1
Bobrie, G	1
Frank, M	1
Chatellier, G	1
Ménard, J	1
Plouin, PF	1
Gupta, A	1
Schiros, CG	1
Gaddam, KK	1
Aban, I	2
Denney, TS	1
Lloyd, SG	2
Oparil, S	2
Dell'Italia, LJ	2
Calhoun, DA	2
Gupta, H	2
Indra, T	1
Holaj, R	1
Štrauch, B	1
Rosa, J	1
Petrák, O	1
Šomlóová, Z	1
Widimský, J	1
Feniman-De-Stefano, GM	1
Zanati-Basan, SG	1
De Stefano, LM	1
Xavier, PS	1
Castro, AD	1
Caramori, JC	1
Barretti, P	1
Franco, RJ	1
Martin, LC	1
Catena, C	4
Colussi, G	3
Novello, M	1
Verheyen, ND	1
Bertin, N	1
Pilz, S	1
Tomaschitz, A	1
Sechi, LA	4
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
Schneider, A	1
Schwab, J	1
Karg, MV	1
Kalizki, T	1
Reinold, A	1
Schneider, MP	1
Schmieder, RE	1
Schmidt, BM	1
Graf, K	1
Hucko, T	1
Stawowy, P	1
Stewart, RA	1
Kerr, AJ	1
Cowan, BR	1
Young, AA	1
Occleshaw, C	1
Richards, AM	1
Edwards, C	1
Whalley, GA	1
Freidlander, D	1
Williams, M	1
Doughty, RN	1
Zeng, I	1
White, HD	1
Grigorian-Shamagian, L	1
Gonzalez-JuAnatey, JR	1
Vazquez, R	1
Cinca, J	1
Bayes-Genis, A	1
Pascual, D	1
Fernandez-Palomeque, C	1
Bardaji, A	1
Almendral, J	1
Nieto, V	1
Macaya, C	1
Jimenez, RP	1
de Luna, AB	1
Karabayeva, AZh	1
Esaian, AM	1
Kayukov, IG	1
Parastaeva, MM	1
Beresneva, ON	1
Kotenko, LV	1
Sevastyanova, IE	1
Jansen, PM	1
Danser, AH	1
Imholz, BP	1
van den Meiracker, AH	1
Ubaid-Girioli, S	1
Adriana de Souza, L	1
Yugar-Toledo, JC	1
Martins, LC	1
Ferreira-Melo, S	1
Coelho, OR	1
Sierra, C	1
Coca, A	1
Pimenta, E	2
Moreno, H	1
Simko, F	4
Pechanova, O	4
Pelouch, V	4
Krajcirovicova, K	4
Mullerova, M	1
Bednarova, K	1
Adamcova, M	3
Paulis, L	4
Stewart, PM	1
Goyal, BR	1
Solanki, N	1
Goyal, RK	1
Mehta, AA	1
Gaddam, K	1
Corros, C	1
Ahmed, M	1
Denney, T	1
Inusah, S	1
Husain, A	1
Veliotes, DG	2
Norton, GR	2
Correia, RJ	1
Strijdom, H	1
Badenhorst, D	1
Brooksbank, R	1
Woodiwiss, AJ	2
Abuannadi, M	1
O'Keefe, JH	1
Baldo, MP	2
Zaniqueli, D	2
Forechi, L	2
Machado, RC	2
Rodrigues, SL	2
Mill, JG	2
López-Andrés, N	1
Martin-Fernandez, B	1
Rossignol, P	1
Zannad, F	2
Lahera, V	1
Fortuno, MA	1
Cachofeiro, V	1
Díez, J	1
Morra, EA	1
Lunz, W	1
Leung, DY	1
Kosmala, W	1
Przewlocka-Kosmala, M	1
Szczepanik-Osadnik, H	1
Mysiak, A	1
O'Moore-Sullivan, T	1
Marwick, TH	1
Colussi, GL	1
Marzano, L	1
Ori, Y	1
Chagnac, A	1
Korzets, A	1
Zingerman, B	1
Herman-Edelstein, M	1
Bergman, M	1
Gafter, U	1
Salman, H	1
Williams, ES	1
Miller, JM	1
Sato, A	3
Hayashi, M	1
Saruta, T	3
Stier, CT	1
Reichek, N	1
Willenbrock, R	1
Phillips, RA	1
Roniker, B	1
Kleiman, J	1
Krause, S	1
Burns, D	1
Williams, GH	2
SoRelle, R	1
Davis, KL	1
Nappi, JM	1
Matsui, Y	1
Jia, N	1
Okamoto, H	1
Kon, S	1
Onozuka, H	1
Akino, M	1
Liu, L	1
Morimoto, J	1
Rittling, SR	1
Denhardt, D	1
Kitabatake, A	1
Uede, T	1
Gumieniak, O	1
Perrier, E	1
Kerfant, BG	1
Lalevee, N	1
Bideaux, P	1
Rossier, MF	1
Richard, S	1
Gómez, AM	1
Benitah, JP	1
Amador, N	1
Encarnación, JJ	1
Guízar, JM	1
Rodríguez, L	1
López, M	1
Kuster, GM	1
Kotlyar, E	1
Rude, MK	1
Siwik, DA	1
Liao, R	1
Colucci, WS	1
Sam, F	1
Deftereos, DA	1
Gray, D	1
Osadchii, O	1
Nishikawa, N	1
Yamamoto, K	1
Sakata, Y	1
Mano, T	1
Yoshida, J	1
Umekawa, S	1
Hori, M	1
Yasuhara, Y	1
Sonoyama, T	1
Harada, A	1
Masuyama, T	1
Roongsritong, C	1
Sutthiwan, P	1
Bradley, J	1
Simoni, J	1
Power, S	1
Meyerrose, GE	1
Taniguchi, I	1
Kawai, M	1
Date, T	1
Yoshida, S	1
Seki, S	1
Taniguchi, M	1
Shimizu, M	1
Mochizuki, S	1
Potácová, A	2
Matúsková, J	3
Lupták, I	1
Pincíková, T	1
Stvrtina, S	1
Pomsár, J	1
Lapenna, R	1
Nadalini, E	1
Chiuch, A	1
Gianfagna, P	1
Auchus, RJ	1
Drazner, MH	1
Fernandes, ML	1
Ferro, EA	1
Beletti, ME	1
Resende, ES	1
Simko, J	1
Hulin, I	1
Janega, P	1
Nicoletti, A	1
Heudes, D	1
Hinglais, N	1
Appay, MD	1
Philippe, M	1
Sassy-Prigent, C	1
Bariety, J	1
Michel, JB	1
Rodríguez, JA	1
Godoy, I	1
Castro, P	1
Quintana, JC	1
Chávez, E	1
Yovanovich, J	1
Corbalán, R	1
Chávez, A	1
Degre, S	1
Detry, JM	1
Unger, P	1
Cosyns, J	1
Brohet, C	1
Kormoss, N	1
Takane, H	1
Coats, AJ	1

Trial	Phase	Enrollment	Study Type	Start Date	Status
PRospectIve Study of Sacubitril/ValsarTan on MyocardIal OxygenatioN and Fibrosis in PatiEnts With Heart Failure and Preserved Ejection Fraction[NCT04128891]	Phase 3	0 participants (Actual)	Interventional	2020-02-01	Withdrawn (stopped due to Funding not approved)
Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist (TOPCAT)[NCT00094302]	Phase 3	3,445 participants (Actual)	Interventional	2006-08-31	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
A Randomised Open Label, Blinded End Point Trial to Compare the Effects of Spironolactone With Chlortalidone on LV Mass in Stage 3 Chronic Kidney Disease (SPIRO-CKD)[NCT02502981]	Phase 4	154 participants (Actual)	Interventional	2014-06-30	Active, not recruiting
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
Mineralocorticoid Receptor, Coronary Microvascular Function, and Cardiac Efficiency in Hypertension[NCT05593055]	Phase 4	75 participants (Anticipated)	Interventional	2023-08-25	Recruiting
Clinical and Therapeutic Implications of Fibrosis in Hypertrophic Cardiomyopathy[NCT00879060]	Phase 4	53 participants (Actual)	Interventional	2007-11-30	Completed
Short-Term Oral Mifepristone for Central Serous Chorioretinopathy. A Placebo-controlled Dose Ranging Study of Mifepristone in the Treatment of CSC (STOMP-CSC)[NCT02354170]	Phase 2	16 participants (Actual)	Interventional	2015-01-31	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.

Absolute Change in Serum Markers of Collagen Turnover (Micrograms/L) Over a One-year Follow-up Period in the Spironolactone Group Compared to Placebo.

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

Specific variables of collagen turnover markers that will be evaluated include markers of collagen synthesis (PINP, PIIINP), and marker of collagen degradation (ICTP). A two-sample t-test was used to compare the differences between these collagen turnover markers at baseline and the absolute differences in change from baseline to 12 months of follow-up. (NCT00879060)
Timeframe: The time points measured were at Baseline and at 12 Months (Follow-Up).

Assessment of Cardiac Mass and Fibrosis by Cardiac Magnetic Resonance Imaging (CMR) - Left Atrial Dimension (in mm)

Intervention	micrograms/L (Mean)
	Baseline (PINP)	12 Months (PINP)	Baseline (PIIINP)	12 Months (PIIINP)	Baseline (ICTP)	12 Months (ICTP)
Placebo Control	2.1	0.6	4.5	1.6	2.5	-2.3
Spironolactone	2.1	0.7	4.7	2.0	2.2	2.7

CMR will be utilized as it has superior reproducibility (as compared to 2-D echocardiography). Late Gadolinium Enhancement (LGE) Assessment of myocardial fibrosis by CMR will be expressed as a percentage of left ventricular mass (%LV), maximum left ventricular wall thickness (in mm), left ventricular end-diastolic cavity size (in mm/m^2), and left atrial dimension (in mm). (NCT00879060)
Timeframe: The time points measured were at Baseline and at 12 Months (Follow-Up)

Assessment of Cardiac Mass and Fibrosis by Cardiac Magnetic Resonance Imaging (CMR) - Left Ventricular End-Diastolic (LVED) Cavity Size (in mm/m^2)

Intervention	millimeters (Mean)
	Left Atrial Dimension (Baseline)	Left Atrial Dimension (12-Month Follow-Up)
Placebo Control	41	40
Spironolactone	40	40

CMR will be utilized as it has superior reproducibility (as compared to 2-D echocardiography). Late Gadolinium Enhancement (LGE) Assessment of myocardial fibrosis by CMR will be expressed as a percentage of left ventricular mass (%LV), maximum left ventricular wall thickness (in mm), left ventricular end-diastolic (LVED) cavity size (in mm/m^2), and left atrial dimension (in mm). (NCT00879060)
Timeframe: The time points measured were at Baseline and at 12 Months (Follow-Up)

Assessment of Cardiac Mass and Fibrosis by Cardiac Magnetic Resonance Imaging (CMR) - Maximum Left Ventricular Wall Thickness (in mm)

Intervention	mm/m^2 (Mean)
	LVED Cavity Size (Baseline)	LVED Cavity Size (12-Month Follow-Up)
Placebo Control	145	146
Spironolactone	133	129

Assessment of Cardiac Mass and Fibrosis by Cardiac Magnetic Resonance Imaging (CMR) - Percentage of Left Ventricular Mass (%LV)

Intervention	millimeters (Mean)
	Maximum Left Ventricular Wall Thickness (Baseline)	Maximum Left Ventricular Wall Thickness (12-Month Follow-Up)
Placebo Control	21	19
Spironolactone	22	22

Measure of Functional Capacity: Peak Oxygen Consumption With Exercise

Intervention	Percentage of Total LV Mass (Mean)
	LGE Assessment of Myocardial Fibrosis (Baseline)	LGE Assessment of Myocardial Fibrosis (12-Month Follow-Up)
Placebo Control	2.5	2.8
Spironolactone	1.1	1.8

This data was collected at baseline, prior to drug administration, and again at 12-months of follow-up to determine if spironolactone improves a subject's functional capacity during exercise (peak oxygen consumption levels/peak VO2). Peak VO2 levels were measured in ml/kg/min. (NCT00879060)
Timeframe: The time points measured were at Baseline and at 12 Months (Follow-Up).

Measure of Heart Failure Symptoms According to the New York Heart Association Functional Class

Intervention	ml/kg/min (Mean)
	Peak VO2 (Baseline)	Peak VO2 (12-Month Follow-Up)
Placebo Control	28	29
Spironolactone	30	29

This data was collected at baseline, prior to drug administration, and again at 12-months of follow-up to assess heart failure symptoms according to the New York Heart Association (NYHA) functional class, which is an estimate of a patients functional ability. The NYHA functional classes include: Class I (no limitation of physical activity), Class II (slight limitation of physical activity), Class III (marked limitation of physical activity), and Class IV (unable to carry out any physical acitivity without discomfort). (NCT00879060)
Timeframe: Time points were measured at Baseline and again at 12 months (follow-up)

Measure of Indices of Diastolic Function by Tissue Doppler Echocardiography (Septal E/e')

Intervention	score on a scale (Mean)
	NYHA Class (Baseline)	NYHA Class (12-Month Follow Up)
Placebo Control	1.5	1.6
Spironolactone	1.6	1.7

This data was collected at baseline, prior to drug administration, and again at 12-months of follow-up to measure indices of diastolic function by Tissue Doppler Echocardiography using the Septal E/e' ratio. (NCT00879060)
Timeframe: The time points measured were at Baseline and at 12 Months (Follow-Up).

Article	Year
Research Progress on the Efficacy and Safety of Spironolactone in Reversing Left Ventricular Hypertrophy in Hemodialysis Patients. Drug design, development and therapy, 2023, Volume: 17 Topics: Aldosterone; Heart Failure; Humans; Hypertrophy, Left Ventricular; Multicenter Studies as Topic; Pro	2023
Aldosterone-receptor antagonism in hypertension. Journal of hypertension, 2009, Volume: 27, Issue:4 Topics: Albuminuria; Aldosterone; Angiotensin-Converting Enzyme Inhibitors; Animals; Arrhythmias, Cardiac; D	2009
Review article: eplerenone: an underused medication? Journal of cardiovascular pharmacology and therapeutics, 2010, Volume: 15, Issue:4 Topics: Cardiovascular Diseases; Eplerenone; Heart Failure; Humans; Hyperkalemia; Hypertension; Hypertrophy,	2010
The role of mineralocorticoid receptor antagonists in patients with American College of Cardiology/American Heart Association stage B heart failure. Heart failure clinics, 2012, Volume: 8, Issue:2 Topics: Adrenal Glands; Aldosterone; Angiotensin-Converting Enzyme Inhibitors; Animals; Enalapril; Endotheli	2012
Eplerenone: a selective aldosterone blocker. Cardiovascular drug reviews, 2003,Fall, Volume: 21, Issue:3 Topics: Animals; Clinical Trials as Topic; Eplerenone; Heart Failure; Humans; Hypertension; Hypertrophy, Lef	2003
The cardiovascular effects of eplerenone, a selective aldosterone-receptor antagonist. Clinical therapeutics, 2003, Volume: 25, Issue:11 Topics: Area Under Curve; Clinical Trials as Topic; Drug Interactions; Eplerenone; Humans; Hyperkalemia; Hyp	2003
Mineralocorticoid receptor antagonists and hypertension: is there a rationale? Current hypertension reports, 2004, Volume: 6, Issue:4 Topics: Albuminuria; Aldosterone; Animals; Drug Therapy, Combination; Eplerenone; Humans; Hyperkalemia; Hype	2004
"Escape" of aldosterone production in patients with left ventricular dysfunction treated with an angiotensin converting enzyme inhibitor: implications for therapy. Cardiovascular drugs and therapy, 1995, Volume: 9, Issue:1 Topics: Aldosterone; Angiotensin-Converting Enzyme Inhibitors; Drug Evaluation; Heart Failure; Humans; Hyper	1995

Article	Year
EFFICACY OF SPIRONOLACTONE IN ANTIHYPERTENSIVE THERAPY IN PATIENTS WITH RESISTANT HYPERTENSION IN COMBINATION WITH RHEUMATOID ARTHRITIS. Georgian medical news, 2020, Issue:309 Topics: Aged; Antihypertensive Agents; Arthritis, Rheumatoid; Echocardiography; Female; Humans; Hypertension	2020
A randomized, multicenter, open-label, blinded end point trial comparing the effects of spironolactone to chlorthalidone on left ventricular mass in patients with early-stage chronic kidney disease: Rationale and design of the SPIRO-CKD trial. American heart journal, 2017, Volume: 191 Topics: Adult; Aged; Chlorthalidone; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Fo	2017
Myocardial fibrosis and QTc are reduced following treatment with spironolactone or amiloride in stroke survivors: a randomised placebo-controlled cross-over trial. International journal of cardiology, 2013, Oct-15, Volume: 168, Issue:6 Topics: Aged; Amiloride; Cross-Over Studies; Diuretics; Double-Blind Method; Female; Fibrosis; Heart Disease	2013
Cardiac structure and function in heart failure with preserved ejection fraction: baseline findings from the echocardiographic study of the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist trial. Circulation. Heart failure, 2014, Volume: 7, Issue:1 Topics: Aged; Aged, 80 and over; Double-Blind Method; Echocardiography; Female; Heart Atria; Heart Failure;	2014
Cardiac structure and function in heart failure with preserved ejection fraction: baseline findings from the echocardiographic study of the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist trial. Circulation. Heart failure, 2014, Volume: 7, Issue:1 Topics: Aged; Aged, 80 and over; Double-Blind Method; Echocardiography; Female; Heart Atria; Heart Failure;	2014
Cardiac structure and function in heart failure with preserved ejection fraction: baseline findings from the echocardiographic study of the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist trial. Circulation. Heart failure, 2014, Volume: 7, Issue:1 Topics: Aged; Aged, 80 and over; Double-Blind Method; Echocardiography; Female; Heart Atria; Heart Failure;	2014
Cardiac structure and function in heart failure with preserved ejection fraction: baseline findings from the echocardiographic study of the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist trial. Circulation. Heart failure, 2014, Volume: 7, Issue:1 Topics: Aged; Aged, 80 and over; Double-Blind Method; Echocardiography; Female; Heart Atria; Heart Failure;	2014
Long-term effects of spironolactone in peritoneal dialysis patients. Journal of the American Society of Nephrology : JASN, 2014, Volume: 25, Issue:5 Topics: Adult; Aged; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Drug	2014
Greater efficacy of aldosterone blockade and diuretic reinforcement vs. dual renin-angiotensin blockade for left ventricular mass regression in patients with resistant hypertension. Journal of hypertension, 2014, Volume: 32, Issue:10 Topics: Adolescent; Adult; Aged; Aldosterone; Amiloride; Amlodipine; Angiotensin II Type 1 Receptor Blockers	2014
Long-term effects of adrenalectomy or spironolactone on blood pressure control and regression of left ventricle hypertrophy in patients with primary aldosteronism. Journal of the renin-angiotensin-aldosterone system : JRAAS, 2015, Volume: 16, Issue:4 Topics: Adrenalectomy; Antihypertensive Agents; Blood Pressure; Electrocardiography; Female; Humans; Hyperal	2015
Spironolactone is secure and reduces left ventricular hypertrophy in hemodialysis patients. Therapeutic advances in cardiovascular disease, 2015, Volume: 9, Issue:4 Topics: Adult; Aged; Aldosterone; Blood Pressure; Double-Blind Method; Drug Monitoring; Female; Humans; Hype	2015
Low-dose eplerenone decreases left ventricular mass in treatment-resistant hypertension. Journal of hypertension, 2017, Volume: 35, Issue:5 Topics: Aged; Antihypertensive Agents; Blood Pressure; Coronary Vasospasm; Double-Blind Method; Drug Therapy	2017
A randomized trial of the aldosterone-receptor antagonist eplerenone in asymptomatic moderate-severe aortic stenosis. American heart journal, 2008, Volume: 156, Issue:2 Topics: Aged; Aortic Valve Stenosis; Blood Flow Velocity; Echocardiography, Doppler; Eplerenone; Female; Hum	2008
Aldosterone excess or escape: Treating resistant hypertension. Journal of clinical hypertension (Greenwich, Conn.), 2009, Volume: 11, Issue:5 Topics: Aldosterone; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Bloo	2009
Effect of spironolactone on left ventricular mass and aortic stiffness in early-stage chronic kidney disease: a randomized controlled trial. Journal of the American College of Cardiology, 2009, Aug-04, Volume: 54, Issue:6 Topics: Adolescent; Adult; Aged; Aged, 80 and over; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Con	2009
Effect of spironolactone on left ventricular mass and aortic stiffness in early-stage chronic kidney disease: a randomized controlled trial. Journal of the American College of Cardiology, 2009, Aug-04, Volume: 54, Issue:6 Topics: Adolescent; Adult; Aged; Aged, 80 and over; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Con	2009
Effect of spironolactone on left ventricular mass and aortic stiffness in early-stage chronic kidney disease: a randomized controlled trial. Journal of the American College of Cardiology, 2009, Aug-04, Volume: 54, Issue:6 Topics: Adolescent; Adult; Aged; Aged, 80 and over; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Con	2009
Effect of spironolactone on left ventricular mass and aortic stiffness in early-stage chronic kidney disease: a randomized controlled trial. Journal of the American College of Cardiology, 2009, Aug-04, Volume: 54, Issue:6 Topics: Adolescent; Adult; Aged; Aged, 80 and over; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Con	2009
Rapid reversal of left ventricular hypertrophy and intracardiac volume overload in patients with resistant hypertension and hyperaldosteronism: a prospective clinical study. Hypertension (Dallas, Tex. : 1979), 2010, Volume: 55, Issue:5 Topics: Age of Onset; Cardiac Volume; Creatinine; Diastole; Diuretics; Electrocardiography; Female; Heart; H	2010
A randomized study of the beneficial effects of aldosterone antagonism on LV function, structure, and fibrosis markers in metabolic syndrome. JACC. Cardiovascular imaging, 2011, Volume: 4, Issue:12 Topics: Aged; Analysis of Variance; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme I	2011
Results from late-breaking clinical trial sessions at the American College of Cardiology 51st Annual Scientific Session. Journal of the American College of Cardiology, 2002, Jul-03, Volume: 40, Issue:1 Topics: Adenosine; Angioplasty, Balloon, Coronary; Anti-Arrhythmia Agents; Antihypertensive Agents; Atherect	2002
Relative long-term effects of spironolactone in conjunction with an angiotensin-converting enzyme inhibitor on left ventricular mass and diastolic function in patients with essential hypertension. Hypertension research : official journal of the Japanese Society of Hypertension, 2002, Volume: 25, Issue:6 Topics: Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Blood Flow Velocity; Blood Pressure; Coronary	2002
Effects of eplerenone, enalapril, and eplerenone/enalapril in patients with essential hypertension and left ventricular hypertrophy: the 4E-left ventricular hypertrophy study. Circulation, 2003, Oct-14, Volume: 108, Issue:15 Topics: Adult; Aged; Amlodipine; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Double-B	2003
Effects of eplerenone, enalapril, and eplerenone/enalapril in patients with essential hypertension and left ventricular hypertrophy: the 4E-left ventricular hypertrophy study. Circulation, 2003, Oct-14, Volume: 108, Issue:15 Topics: Adult; Aged; Amlodipine; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Double-B	2003
Effects of eplerenone, enalapril, and eplerenone/enalapril in patients with essential hypertension and left ventricular hypertrophy: the 4E-left ventricular hypertrophy study. Circulation, 2003, Oct-14, Volume: 108, Issue:15 Topics: Adult; Aged; Amlodipine; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Double-B	2003
Effects of eplerenone, enalapril, and eplerenone/enalapril in patients with essential hypertension and left ventricular hypertrophy: the 4E-left ventricular hypertrophy study. Circulation, 2003, Oct-14, Volume: 108, Issue:15 Topics: Adult; Aged; Amlodipine; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Double-B	2003
Effect of losartan and spironolactone on left ventricular mass and heart sympathetic activity in prehypertensive obese subjects: a 16-week randomized trial. Journal of human hypertension, 2005, Volume: 19, Issue:4 Topics: Adult; Antihypertensive Agents; Blood Pressure; Body Mass Index; Diuretics; Double-Blind Method; Ech	2005
Spironolactone improves diastolic function in the elderly. Clinical cardiology, 2005, Volume: 28, Issue:10 Topics: Aged; Aged, 80 and over; Blood Pressure; Coronary Artery Disease; Diastole; Double-Blind Method; Fem	2005
Effects of spironolactone during an angiotensin II receptor blocker treatment on the left ventricular mass reduction in hypertensive patients with concentric left ventricular hypertrophy. Circulation journal : official journal of the Japanese Circulation Society, 2006, Volume: 70, Issue:8 Topics: Aged; Aldosterone; Angiotensin II; Angiotensin II Type 1 Receptor Blockers; Benzimidazoles; Biphenyl	2006
[Effects of ramipril and spironolactone on ventricular remodeling after acute myocardial infarction: randomized and double-blind study]. Revista medica de Chile, 1997, Volume: 125, Issue:6 Topics: Analysis of Variance; Angiotensin-Converting Enzyme Inhibitors; Disease-Free Survival; Double-Blind	1997
Effects of spironolactone-altizide on left ventricular hypertrophy. Acta cardiologica, 1998, Volume: 53, Issue:5 Topics: Benzothiadiazines; Diuretics; Drug Therapy, Combination; Female; Humans; Hypertension; Hypertrophy,	1998
Effects of spironolactone and angiotensin-converting enzyme inhibitor on left ventricular hypertrophy in patients with essential hypertension. Hypertension research : official journal of the Japanese Society of Hypertension, 1999, Volume: 22, Issue:1 Topics: Aldosterone; Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Drug Therapy, Combination; Ec	1999
High serum level of procollagen type III amino-terminal peptide contributes to the efficacy of spironolactone and angiotensin-converting enzyme inhibitor therapy on left ventricular hypertrophy in essential hypertensive patients. Hypertension research : official journal of the Japanese Society of Hypertension, 2001, Volume: 24, Issue:2 Topics: Adult; Angiotensin-Converting Enzyme Inhibitors; Diuretics; Female; Humans; Hypertension; Hypertroph	2001

Article	Year
[Treatment of patients with heart failure and preserved ejection fraction: reliance on clinical phenotypes]. Kardiologiia, 2022, Jul-31, Volume: 62, Issue:7 Topics: Aminobutyrates; Amyloidosis; Angiotensin Receptor Antagonists; Biphenyl Compounds; Heart Failure; Hu	2022
Unique Case of Cardiomyopathy Secondary to Adrenal Adenoma (Primary-Aldosteronism). The Journal of the Association of Physicians of India, 2023, Volume: 71, Issue:1 Topics: Adenoma; Adrenocortical Adenoma; Aldosterone; Cardiomyopathies; Female; Humans; Hyperaldosteronism;	2023
Myocardial global longitudinal strain: An early indicator of cardiac interstitial fibrosis modified by spironolactone, in a unique hypertensive rat model. PloS one, 2019, Volume: 14, Issue:8 Topics: Animals; Cardiotonic Agents; Disease Models, Animal; Echocardiography; Endomyocardial Fibrosis; Hype	2019
Primary aldosteronism and low-renin hypertension: a continuum? Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association, 2013, Volume: 28, Issue:7 Topics: Essential Hypertension; Female; Humans; Hyperaldosteronism; Hypertension; Hypertrophy, Left Ventricu	2013
Eplerenone enhances cardioprotective effects of standard heart failure therapy through matricellular proteins in hypertensive heart failure. Journal of hypertension, 2013, Volume: 31, Issue:11 Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Animals; Blood Pressure; Drug	2013
Eplerenone-mediated regression of electrical activation delays and myocardial fibrosis in heart failure. Journal of cardiovascular electrophysiology, 2014, Volume: 25, Issue:5 Topics: Action Potentials; Animals; Anti-Inflammatory Agents; Arrhythmias, Cardiac; Cardiac Pacing, Artifici	2014
Effect of spironolactone on diastolic function in hypertensive left ventricular hypertrophy. Journal of human hypertension, 2015, Volume: 29, Issue:4 Topics: Adult; Biomarkers; Blood Pressure; Case-Control Studies; Collagen; Diastole; Female; Humans; Hyperte	2015
Dietary Salt Intake Is a Determinant of Cardiac Changes After Treatment of Primary Aldosteronism: A Prospective Study. Hypertension (Dallas, Tex. : 1979), 2016, Volume: 68, Issue:1 Topics: Adrenalectomy; Adult; Analysis of Variance; Cohort Studies; Echocardiography, Doppler; Female; Follo	2016
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
Cardiac benefits of mineralocorticoid receptor inhibition in renal failure. Hypertension (Dallas, Tex. : 1979), 2008, Volume: 52, Issue:2 Topics: Aldosterone; Animals; Cohort Studies; Disease Models, Animal; Humans; Hypertrophy, Left Ventricular;	2008
Association of blood pressure and its evolving changes with the survival of patients with heart failure. Journal of cardiac failure, 2008, Volume: 14, Issue:7 Topics: Adrenergic beta-Antagonists; Aged; Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Calcium	2008
Effect of spironolactone on hypertrophy of left ventricular myocardium in wistar rats with experimental uremia. Bulletin of experimental biology and medicine, 2008, Volume: 145, Issue:6 Topics: Aldosterone; Animals; Creatinine; Electrolytes; Hypertrophy, Left Ventricular; Kidney Failure, Chron	2008
Effect of melatonin, captopril, spironolactone and simvastatin on blood pressure and left ventricular remodelling in spontaneously hypertensive rats. Journal of hypertension. Supplement : official journal of the International Society of Hypertension, 2009, Volume: 27, Issue:6 Topics: Animals; Antihypertensive Agents; Antioxidants; Blood Pressure; Captopril; Hypertrophy, Left Ventric	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
Pharmacotherapy: Cardiovascular effects of aldosterone blockade in CKD. Nature reviews. Cardiology, 2009, Volume: 6, Issue:11 Topics: Aortic Diseases; Chronic Disease; Humans; Hyperkalemia; Hypertrophy, Left Ventricular; Kidney Diseas	2009
Impact of aldosterone receptor blockade on the deleterious cardiac effects of adrenergic activation in hypertensive rats. Journal of cardiovascular pharmacology, 2010, Volume: 56, Issue:2 Topics: Adrenergic beta-Agonists; Animals; Apoptosis; Blood Pressure; Cardiomyopathy, Dilated; Hypertension;	2010
Hyperaldosteronism and left ventricular hypertrophy. Hypertension (Dallas, Tex. : 1979), 2010, Volume: 56, Issue:3 Topics: Humans; Hyperaldosteronism; Hypertrophy, Left Ventricular; Insecticide-Treated Bednets; Spironolacto	2010
Effects of spironolactone in spontaneously hypertensive adult rats subjected to high salt intake. Clinics (Sao Paulo, Brazil), 2011, Volume: 66, Issue:3 Topics: Analysis of Variance; Animals; Blood Pressure; Hypertension; Hypertrophy, Left Ventricular; Linear M	2011
A role for cardiotrophin-1 in myocardial remodeling induced by aldosterone. American journal of physiology. Heart and circulatory physiology, 2011, Volume: 301, Issue:6 Topics: Aldosterone; Animals; Blood Pressure; Blotting, Western; Collagen; Cytokines; Disease Models, Animal	2011
Long-term use of low-dose spironolactone in spontaneously hypertensive rats: effects on left ventricular hypertrophy and stiffness. Pharmacological reports : PR, 2011, Volume: 63, Issue:4 Topics: Age Factors; Animals; Blood Pressure; Hypertension; Hypertrophy, Left Ventricular; Male; Mineralocor	2011
Aldosterone blockade in metabolic syndrome: hitting the target or still missing some links? JACC. Cardiovascular imaging, 2011, Volume: 4, Issue:12 Topics: Female; Humans; Hypertrophy, Left Ventricular; Male; Metabolic Syndrome; Mineralocorticoid Receptor	2011
Predictive factors of left ventricular mass changes after treatment of primary aldosteronism. Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme, 2012, Volume: 44, Issue:3 Topics: Adrenalectomy; Adult; Aldosterone; Blood Pressure; Female; Heart Ventricles; Humans; Hyperaldosteron	2012
Regression of left ventricular hypertrophy in patients with primary aldosteronism/low-renin hypertension on low-dose spironolactone. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association, 2013, Volume: 28, Issue:7 Topics: Aged; Blood Pressure Determination; Echocardiography; Essential Hypertension; Female; Follow-Up Stud	2013
Two better than one. Circulation, 2003, Oct-14, Volume: 108, Issue:15 Topics: Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Animals; Class Ib Phosphatidylinositol 3-Kina	2003
Role of osteopontin in cardiac fibrosis and remodeling in angiotensin II-induced cardiac hypertrophy. Hypertension (Dallas, Tex. : 1979), 2004, Volume: 43, Issue:6 Topics: Aldosterone; Angiotensin II; Animals; Apoptosis; Blood Pressure; Cardiomegaly; Cell Size; Eplerenone	2004
Mineralocorticoid receptor antagonism prevents the electrical remodeling that precedes cellular hypertrophy after myocardial infarction. Circulation, 2004, Aug-17, Volume: 110, Issue:7 Topics: Action Potentials; Animals; Aorta, Abdominal; Aortic Valve Stenosis; Calcium; Calcium Channels, L-Ty	2004
Mineralocorticoid receptor inhibition ameliorates the transition to myocardial failure and decreases oxidative stress and inflammation in mice with chronic pressure overload. Circulation, 2005, Feb-01, Volume: 111, Issue:4 Topics: Animals; Aorta; Apoptosis; Blood Pressure; Cell Size; Chronic Disease; Constriction, Pathologic; Dru	2005
Aldosterone receptor blockade prevents the transition to cardiac pump dysfunction induced by beta-adrenoreceptor activation. Hypertension (Dallas, Tex. : 1979), 2005, Volume: 45, Issue:5 Topics: Adrenergic beta-Agonists; Animals; Collagen; Echocardiography; Heart; Hypertension; Hypertrophy, Lef	2005
Long-term effect of spironolactone on cardiac structure as assessed by analysis of ultrasonic radio-frequency signals in patients with ventricular hypertrophy. Circulation journal : official journal of the Japanese Circulation Society, 2005, Volume: 69, Issue:11 Topics: Adult; Aged; Animals; Echocardiography, Doppler; Female; Fibrosis; Heart Ventricles; Humans; Hypertr	2005
Spontaneous, L-arginine-induced and spironolactone-induced regression of protein remodeling of the left ventricle in L-NAME-induced hypertension. Physiological research, 2007, Volume: 56 Suppl 2 Topics: Animals; Arginine; Blood Pressure; Collagen; Hypertension; Hypertrophy, Left Ventricular; Male; Mine	2007
Spironolactone differently influences remodeling of the left ventricle and aorta in L-NAME-induced hypertension. Physiological research, 2007, Volume: 56 Suppl 2 Topics: Animals; Antihypertensive Agents; Aorta; Blood Pressure; Cell Proliferation; DNA Replication; Heart	2007
Long-term cardiac effects of adrenalectomy or mineralocorticoid antagonists in patients with primary aldosteronism. Hypertension (Dallas, Tex. : 1979), 2007, Volume: 50, Issue:5 Topics: Adenoma; Adrenal Gland Neoplasms; Adrenalectomy; Aldosterone; Antihypertensive Agents; Female; Follo	2007
Will the lessons from primary aldosteronism change the treatment of hypertension and left ventricular hypertrophy? Hypertension (Dallas, Tex. : 1979), 2007, Volume: 50, Issue:5 Topics: Adrenalectomy; Blood Pressure; Cohort Studies; Comorbidity; Follow-Up Studies; Humans; Hyperaldoster	2007
Spironolactone effects on myocardium changes induced by thyroid hormone in rats. Arquivos brasileiros de cardiologia, 2007, Volume: 89, Issue:6 Topics: Analysis of Variance; Animals; Body Weight; Heart; Heart Rate; Hypertrophy, Left Ventricular; Male;	2007
Regression of left ventricular hypertrophy and aortic remodelling in NO-deficient hypertensive rats: effect of L-arginine and spironolactone. Acta physiologica (Oxford, England), 2008, Volume: 194, Issue:1 Topics: Animals; Aorta; Arginine; Fibrosis; Hypertension; Hypertrophy, Left Ventricular; Male; Mineralocorti	2008
Left ventricular fibrosis in renovascular hypertensive rats. Effect of losartan and spironolactone. Hypertension (Dallas, Tex. : 1979), 1995, Volume: 26, Issue:1 Topics: Angiotensin II; Angiotensin Receptor Antagonists; Animals; Antihypertensive Agents; Biochemical Phen	1995
Exciting new drugs on the horizon - eplerenone, a selective aldosterone receptor antagonist (SARA). International journal of cardiology, 2001, Volume: 80, Issue:1 Topics: Eplerenone; Heart Failure; Humans; Hypertrophy, Left Ventricular; Mineralocorticoid Receptor Antagon	2001

Intervention	Ratio (Mean)
	Diastolic Function (Baseline)	Diastolic Function (12-month Follow-Up)
Placebo Control	15	13
Spironolactone	14	13

spironolactone and Hypertrophy, Left Ventricular

Research Excerpts

Research

Studies (69)

Authors

Clinical Trials (8)

Trial Overview

Trial Outcomes

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

Absolute Change in Serum Markers of Collagen Turnover (Micrograms/L) Over a One-year Follow-up Period in the Spironolactone Group Compared to Placebo.

Assessment of Cardiac Mass and Fibrosis by Cardiac Magnetic Resonance Imaging (CMR) - Left Atrial Dimension (in mm)

Assessment of Cardiac Mass and Fibrosis by Cardiac Magnetic Resonance Imaging (CMR) - Left Ventricular End-Diastolic (LVED) Cavity Size (in mm/m^2)

Assessment of Cardiac Mass and Fibrosis by Cardiac Magnetic Resonance Imaging (CMR) - Maximum Left Ventricular Wall Thickness (in mm)

Assessment of Cardiac Mass and Fibrosis by Cardiac Magnetic Resonance Imaging (CMR) - Percentage of Left Ventricular Mass (%LV)

Measure of Functional Capacity: Peak Oxygen Consumption With Exercise

Measure of Heart Failure Symptoms According to the New York Heart Association Functional Class

Measure of Indices of Diastolic Function by Tissue Doppler Echocardiography (Septal E/e')

Reviews

Trials

Other Studies