spironolactone and Hypertension 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.

Hypertension: Persistently high systemic arterial BLOOD PRESSURE. Based on multiple readings (BLOOD PRESSURE DETERMINATION), hypertension is currently defined as when SYSTOLIC PRESSURE is consistently greater than 140 mm Hg or when DIASTOLIC PRESSURE is consistently 90 mm Hg or more.

Research Excerpts

Excerpt	Relevance	Reference
"The mineralocorticoid receptor antagonist spironolactone lowers blood pressure in patients with resistant hypertension despite antihypertensive treatment with angiotensin-converting inhibitors (ACEi) and angiotensin-II receptor blockers (ARB)."	9.51	The mineralocorticoid receptor blocker spironolactone lowers plasma interferon-γ and interleukin-6 in patients with type 2 diabetes and treatment-resistant hypertension. ( Fonseca, MPD; Jacobsen, IA; Jensen, BL; Ketelhuth, DFJ; Oxlund, CS; Palarasah, Y; Stubbe, J; Svenningsen, P; Thangaraj, SS, 2022)
"The AMBER trial demonstrated that concomitant use of patiromer enabled the more persistent use of spironolactone by reducing the risk of hyperkalaemia in patients with resistant hypertension and advanced chronic kidney disease."	9.34	Patiromer versus placebo to enable spironolactone use in patients with resistant hypertension and chronic kidney disease (AMBER): results in the pre-specified subgroup with heart failure. ( Ackourey, G; Agarwal, R; Arthur, S; Mayo, MR; Rossignol, P; Warren, S; White, WB; Williams, B, 2020)
"Spironolactone is effective at reducing blood pressure in patients with uncontrolled resistant hypertension."	9.30	Patiromer versus placebo to enable spironolactone use in patients with resistant hypertension and chronic kidney disease (AMBER): a phase 2, randomised, double-blind, placebo-controlled trial. ( Agarwal, R; Garza, D; Ma, J; Mayo, MR; Romero, A; Rossignol, P; Warren, S; White, WB; Williams, B, 2019)
"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)
"We identified patients with RHTN, defined as baseline systolic blood pressure (SBP) between 140 and 160 mm Hg on 3 or more medications, in the Americas cohort of the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist trial, in which patients with HFpEF were randomized to spironolactone vs."	9.27	Spironolactone and Resistant Hypertension in Heart Failure With Preserved Ejection Fraction. ( Claggett, BL; Liu, J; Pitt, B; Rossignol, P; Solomon, S; Vardeny, O; Zannad, F, 2018)
"Renal denervation and spironolactone have both been proposed for the treatment of resistant hypertension, but their effects on preclinical target organ damage have not been compared."	9.27	Organ damage changes in patients with resistant hypertension randomized to renal denervation or spironolactone: The DENERVHTA (Denervación en Hipertensión Arterial) study. ( Armario, P; Clarà, A; de la Sierra, A; Molina, L; Oliveras, A; Pareja, J; Pascual, J; Sans, L; Vázquez, S, 2018)
"The mineralocorticoid receptor antagonist spironolactone significantly reduces albuminuria in patients with diabetes."	9.27	Predicting albuminuria response to spironolactone treatment with urinary proteomics in patients with type 2 diabetes and hypertension. ( Heerspink, HJL; Jacobsen, IA; Lindhardt, M; Mischak, H; Oxlund, C; Persson, F; Rossing, P; Zürbig, P, 2018)
"Eplerenone is reported to reduce the development of atrial fibrillation (AF)."	9.24	Eplerenone might affect atrial fibrosis in patients with hypertension. ( Fukunami, M; Furukawa, Y; Iwasaki, Y; Kawasaki, M; Kikuchi, A; Morita, T; Okuyama, Y; Sakata, Y; Tamaki, S; Yamada, T, 2017)
"This study investigated the effects and safety of eplerenone or thiazide diuretics in patients with hypertension and albuminuria (pretreatment urinary albumin/creatinine ratio ≥10 mg/gCr) treated with an angiotensin II receptor blocker."	9.24	Antialbuminuric effect of eplerenone in comparison to thiazide diuretics in patients with hypertension. ( Dohi, K; Fujimoto, N; Ichikawa, T; Isaka, N; Ito, M; Kitamura, T; Koyabu, S; Makino, K; Nakamura, M; Nishikawa, M; Ogura, T; Okamoto, S; Okubo, S; Sawai, T; Tamaru, S; Yamada, T, 2017)
" Prostasin was measured in plasma and urine from type 2 diabetic patients with resistant hypertension (n = 112) randomized to spironolactone/placebo in a clinical trial."	9.24	Albuminuria is associated with an increased prostasin in urine while aldosterone has no direct effect on urine and kidney tissue abundance of prostasin. ( Bistrup, C; Hansen, MR; Hansen, PB; Hinrichs, GR; Jacobsen, IA; Jensen, BL; Kurt, B; Oxlund, C; Schwarzensteiner, I; Stæhr, M; Svenningsen, P; Thuesen, AD; Toft, A, 2017)
"This randomized, multicenter study compared the relative efficacy of renal denervation (RDN) versus pharmacotherapy alone in patients with true resistant hypertension and assessed the effect of spironolactone addition."	9.22	Role of Adding Spironolactone and Renal Denervation in True Resistant Hypertension: One-Year Outcomes of Randomized PRAGUE-15 Study. ( Bednář, F; Branny, M; Čurila, K; Holaj, R; Indra, T; Jiravský, O; Kociánová, E; Krátká, Z; Lambert, L; Nykl, I; Petrák, O; Rappová, G; Rosa, J; Štrauch, B; Táborský, M; Toušek, P; Václavík, J; Waldauf, P; Widimský, J; Widimský, P; Zelinka, T, 2016)
"Low-dose spironolactone has been proven to be effective for resistant hypertension in the general population, but this has yet to be confirmed in type 2 diabetic (T2DM) patients."	9.22	Effect of low-dose spironolactone on resistant hypertension in type 2 diabetes mellitus: a randomized controlled trial in a sub-Saharan African population. ( Djoumessi, RN; Essouma, M; Kaze, FF; Kengne, AP; Mbanya, JC; Menanga, AP; Noubiap, JJ; Sobngwi, E, 2016)
"The Eplerenone on parathyroid hormone levels in patients with primary hyperparathyroidism (EPATH) trial is a single-center, randomized, double-blind, parallel-group, placebo-controlled trial."	9.22	Effect of eplerenone on parathyroid hormone levels in patients with primary hyperparathyroidism: results from the EPATH randomized, placebo-controlled trial. ( Aberer, F; Alesutan, I; Belyavskiy, E; Brussee, H; Dimai, HP; Fahrleitner-Pammer, A; Gaksch, M; Grübler, M; Haas, J; Hartaigh, BÓ; Horina, JH; Lang, F; März, W; Meinitzer, A; Ofner-Ziegenfuss, L; Pieske, B; Pieske-Kraigher, E; Pilz, S; Ritz, E; Rus-Machan, J; Schwetz, V; Stiegler, C; Tomaschitz, A; Verheyen, N; Verheyen, S; Voelkl, J, 2016)
"Both renal denervation (RDN) and spironolactone have been proposed for the treatment of resistant hypertension."	9.22	Spironolactone versus sympathetic renal denervation to treat true resistant hypertension: results from the DENERVHTA study - a randomized controlled trial. ( Armario, P; Clarà, A; De la Sierra, A; Oliveras, A; Pascual, J; Sans-Atxer, L; Vázquez, S, 2016)
"This prospective, randomized, open-label multicenter trial evaluated the efficacy of catheter-based renal denervation (Symplicity, Medtronic) versus intensified pharmacological treatment including spironolactone (if tolerated) in patients with true-resistant hypertension."	9.20	Randomized comparison of renal denervation versus intensified pharmacotherapy including spironolactone in true-resistant hypertension: six-month results from the Prague-15 study. ( Bednář, F; Branny, M; Čurila, K; Holaj, R; Jiravský, O; Kociánová, E; Nykl, I; Petrák, O; Rosa, J; Šomlóová, Z; Štrauch, B; Táborský, M; Toušek, P; Václavík, J; Waldauf, P; Widimský, J; Widimský, P; Zelinka, T, 2015)
"Spironolactone was the most effective add-on drug for the treatment of resistant hypertension."	9.20	Spironolactone versus placebo, bisoprolol, and doxazosin to determine the optimal treatment for drug-resistant hypertension (PATHWAY-2): a randomised, double-blind, crossover trial. ( Brown, MJ; Caulfield, MJ; Cruickshank, JK; Ford, I; MacDonald, TM; Mackenzie, I; McInnes, G; Morant, S; Padmanabhan, S; Salsbury, J; Sever, P; Webb, DJ; Williams, B, 2015)
"The PATHWAY-2 study, funded by the British Heart Foundation, randomised 335 patients with resistant hypertension (already treated according to guidelines) to sequentially receive 12 weeks of spironolactone (25-50 mg), bisoprolol (5-10 mg), doxazosin (4-8 mg modified release) and placebo."	9.20	[PATHWAY-2 Study: spironolactone vs placebo, bisoprolol and doxazosin to determine optimal treatment of resistant hypertension. Spironolactone high effective in lowering blood pressure in drug resistant hypertension]. ( Widimský, J, 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)
"The purpose of this study was to evaluate the effects of spironolactone on dialysis patients with refractory hypertension and possible adverse effects."	9.19	Effects of spironolactone on dialysis patients with refractory hypertension: a randomized controlled study. ( Chen, J; Ni, X; Wu, F; Xia, M; Ying, G; Zhang, J; Zhang, P, 2014)
"Addition of low-dose eplerenone to renin-angiotensin system inhibitors might have renoprotective effects through reduction of albuminuria in hypertensive patients with non-diabetic chronic kidney disease, without serious safety concerns."	9.19	Anti-albuminuric effect of the aldosterone blocker eplerenone in non-diabetic hypertensive patients with albuminuria: a double-blind, randomised, placebo-controlled trial. ( Ando, K; Arakawa, Y; Fujita, T; Kaname, S; Ohtsu, H; Uchida, S, 2014)
"This study was designed to assess the effect of the addition of low-dose spironolactone on blood pressure (BP) in patients with resistant arterial hypertension."	9.19	Effect of spironolactone in resistant arterial hypertension: a randomized, double-blind, placebo-controlled trial (ASPIRANT-EXT). ( Jarkovský, J; Kociánová, E; Sedlák, R; Táborský, M; Václavík, J, 2014)
"There are currently limited data on whether the effect of spironolactone in patients with resistant arterial hypertension depends on age and sex."	9.19	Effect of spironolactone in patients with resistant arterial hypertension in relation to age and sex: insights from the aspirant trial. ( Jarkovsky, J; Kocianova, E; Sedlak, R; Taborsky, M; Vaclavik, J, 2014)
"The primary objective of this study was to evaluate the antihypertensive effect of low dose spironolactone added to triple therapy for resistant hypertension in patients with type 2 diabetes measured by ambulatory monitoring."	9.17	Low dose spironolactone reduces blood pressure in patients with resistant hypertension and type 2 diabetes mellitus: a double blind randomized clinical trial. ( Gram, J; Henriksen, JE; Jacobsen, IA; Oxlund, CS; Schousboe, K; Tarnow, L, 2013)
" We wanted to test the hypotheses that amiloride and spironolactone induced potassium retention reduces ambulatory blood pressure (ABP) and central blood pressure (CBP) during baseline conditions and after furosemide and that the tubular transport via the epithelial sodium channels (ENaCs) and aquaporin-2 (AQP2) water channels was increased by furosemide in arterial hypertension."	9.17	Effect of amiloride and spironolactone on renal tubular function and central blood pressure in patients with arterial hypertension during baseline conditions and after furosemide: a double-blinded, randomized, placebo-controlled crossover trial. ( Jensen, JM; Larsen, T; Lauridsen, TG; Matthesen, SK; Pedersen, EB; Vase, H, 2013)
"There are currently limited data about whether the effect of spironolactone in patients with resistant arterial hypertension depends on baseline blood pressure and the presence of a secondary cause of hypertension."	9.17	The effect of spironolactone in patients with resistant arterial hypertension in relation to baseline blood pressure and secondary causes of hypertension. ( Jarkovsky, J; Kocianova, E; Sedlak, R; Taborsky, M; Vaclavik, J, 2013)
"Recent studies from our laboratory indicate that chlorthalidone triggers persistent activation of the sympathetic nervous system and promotes insulin resistance in hypertensive patients, independent of serum potassium."	9.16	Spironolactone prevents chlorthalidone-induced sympathetic activation and insulin resistance in hypertensive patients. ( Adams-Huet, B; Arbique, D; Auchus, RJ; Price, A; Raheja, P; Vongpatanasin, W; Wang, Z, 2012)
"If spironolactone proves effective, it might become the standard of treatment in patients with resistant arterial hypertension."	9.15	Addition of spironolactone in patients with resistant arterial hypertension (ASPIRANT)--study protocol. ( Husar, R; Kocianova, E; Navratil, K; Plachy, M; Plasek, J; Sedlak, R; Taborsky, M; Vaclavik, J, 2011)
" 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 role of spironolactone in resistant hypertension management is unclear."	9.14	Efficacy of spironolactone therapy in patients with true resistant hypertension. ( de Souza, F; Fiszman, R; Muxfeldt, E; Salles, G, 2010)
"The aim of the study was evaluation of spironolactone effect on concentration of endothelin-1 (ET-1 - vasoconstrictive substance produced by endothelial cells) and aldosterone (Ald) and plasma renin activity (PRA) in patients with primary arterial hypertension (AH): group A--smoking patients (11 individuals) in comparison with group B--non-smoking ones (12 individuals)."	9.14	[Does spironolactone use at arterial hypertension therapy protect endothelium also in smoking patients?]. ( Kara-Perz, H; Kosicka, T; Perz, S, 2009)
"To determine the efficacy and safety of eplerenone therapy in children with hypertension."	9.14	The efficacy and safety of the novel aldosterone antagonist eplerenone in children with hypertension: a randomized, double-blind, dose-response study. ( Davis, I; Flynn, JT; Li, JS; Ogawa, M; Portman, R; Pressler, ML; Shi, H, 2010)
"To determine the efficacy of spironolactone (SPIRO) and hydrochlorothiazide (HCTZ) as monotherapy in older patients with hypertension in blood pressure (BP) control and measures of vascular stiffness."	9.14	Spironolactone and hydrochlorothiazide decrease vascular stiffness and blood pressure in geriatric hypertension. ( Kithas, PA; Supiano, MA, 2010)
"In the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (n=6632), eplerenone-associated reduction in all-cause mortality was significantly greater in those with a history of hypertension (Hx-HTN)."	9.13	History of hypertension and eplerenone in patients with acute myocardial infarction complicated by heart failure. ( Ahmed, A; Aschermann, M; Cardoso, JS; Corbalán, R; Krum, H; Love, TE; Nicolau, J; Parkhomenko, A; Pitt, B; Shi, H; Solomon, H; Zannad, F, 2008)
"The aim of this prospective, randomised, open-label, blinded-end point study was to compare the efficacy and safety of eplerenone versus spironolactone in patients with bilateral idiopathic hyperaldosteronism (IHA)."	9.13	Spironolactone versus eplerenone for the treatment of idiopathic hyperaldosteronism. ( Anagnostis, P; Athyros, VG; Kakafika, AI; Karagiannis, A; Mikhailidis, DP; Pagourelias, ED; Papageorgiou, A; Tziomalos, K, 2008)
" Studies comparing the effect of spironolactone to placebo in patients with hypertension and DM were included."	9.12	A systematic review and meta-analysis of effects of spironolactone on blood pressure, glucose, lipids, renal function, fibrosis and inflammation in patients with hypertension and diabetes. ( Abudoyreyimu, R; Heizati, M; Li, N; Lin, M; Nurula, M; Wang, L; Wang, Z; Wu, Z; Yang, Z, 2021)
"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)
"Spironolactone is recommended as fourth-line therapy for essential hypertension despite few supporting data for this indication."	9.12	Effect of spironolactone on blood pressure in subjects with resistant hypertension. ( Chapman, N; Dahlöf, B; Dobson, J; Poulter, NR; Sever, PS; Wedel, H; Wilson, S, 2007)
" It is not known if subjects with a high ratio have aldosteronism or aldosterone-sensitive hypertension is debated but it is important to know whether spironolactone is superior to other diuretics such as bendroflumethiazide in this setting."	9.12	Does the aldosterone:renin ratio predict the efficacy of spironolactone over bendroflumethiazide in hypertension? A clinical trial protocol for RENALDO (RENin-ALDOsterone) study. ( Alhashmi, K; Connell, JM; Ford, I; MacDonald, TM; McInnes, GT; McMahon, AD; Parthasarathy, HK; Struthers, AD, 2007)
"This study compared the efficacy and tolerability of eplerenone and enalapril in 499 patients with stage 1 or 2 hypertension who were randomized to receive eplerenone or enalapril for 6 months in a 3-step titration-to-effect study."	9.11	Efficacy of eplerenone versus enalapril as monotherapy in systemic hypertension. ( Burgess, E; Kipnes, MS; Kolloch, RE; Krause, SL; Niegowska, J; Patrick, JL; Roniker, B; Ruilope, LM; Williams, GH, 2004)
"The effect of spironolactone, cilazapril and their combination on albuminuria was examined in a randomized prospective study in female patients with diabetes and hypertension."	9.11	The effect of spironolactone, cilazapril and their combination on albuminuria in patients with hypertension and diabetic nephropathy is independent of blood pressure reduction: a randomized controlled study. ( Amit, M; Berla, M; Kedar, Y; Levi, Z; Rachmani, R; Ravid, M; Slavachevsky, I, 2004)
"This 16-week, multicenter, double-blind, active-controlled, parallel-group, titration-to-effect trial compared the blood pressure and neurohumoral responses of the selective aldosterone blocker eplerenone (100-200 mg/d; n = 86) with those of the angiotensin receptor blocker losartan (50-100 mg/d; n = 82) in patients with low-renin hypertension (active renin < or = 25 pg/mL [< or = 42."	9.11	Effects of eplerenone versus losartan in patients with low-renin hypertension. ( Davidson, RC; Krause, SL; MacDonald, TM; Patrick, JL; Roniker, B; Ruilope, LM; Weinberger, MH; White, WB, 2005)
"Eplerenone, a selective aldosterone blocker (SAB) that is highly specific for the aldosterone receptor, has the potential to be efficacious in the treatment of hypertension."	9.10	Eplerenone, a selective aldosterone blocker, in mild-to-moderate hypertension. ( Krause, SL; Roniker, B; Weinberger, MH; Weiss, RJ, 2002)
"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)
"Eplerenone is a highly selective aldosterone blocker, which is under development for the treatment of hypertension and heart failure."	9.10	Effects of the selective aldosterone blocker eplerenone versus the calcium antagonist amlodipine in systolic hypertension. ( Duprez, D; Krause, S; Kuse-Hamilton, J; Roniker, B; St Hillaire, R; Weber, MA; White, WB, 2003)
"Eplerenone is a highly selective aldosterone blocking agent, which was recently approved for the treatment of hypertension and has also been shown to reduce mortality in post-myocardial infarction patients with heart failure."	9.10	Assessment of the novel selective aldosterone blocker eplerenone using ambulatory and clinical blood pressure in patients with systemic hypertension. ( Carr, AA; Jordan, R; Krause, S; Oigman, W; Roniker, B; White, WB, 2003)
" This study compared LVH regression during treatment with the selective aldosterone blocker eplerenone, enalapril, and their combination in patients with hypertension."	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)
"Previous reports have demonstrated the antihypertensive efficacy of high doses of spironolactone in subjects with primary aldosteronism and, to a lesser degree, subjects with resistant hypertension."	9.10	Efficacy of low-dose spironolactone in subjects with resistant hypertension. ( Calhoun, DA; Nishizaka, MK; Zaman, MA, 2003)
"Eplerenone therapy was effective in the treatment of mild to moderate hypertension over a 14-month period, either as monotherapy or in combination with another antihypertensive agent."	9.10	Long-term safety and efficacy of the selective aldosterone blocker eplerenone in patients with essential hypertension. ( Burgess, ED; Kleiman, JH; Krause, S; Lacourcière, Y; Maurath, C; Oparil, S; Roniker, B; Ruilope-Urioste, LM, 2003)
" 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)
"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)
"The study was undertaken to determine the possible effect of an aldosterone antagonist, spironolactone (SP), on red blood cell sodium-hydrogen exchange (NHE) enhancement in primary aldosteronism (PA) and essential hypertension (EH)."	9.08	Spironolactone prevents Na+/H+ exchange enhancement in primary aldosteronism. ( Koldanov, R; Koren, W; Postnov, IY; Postnov, YV, 1997)
"To investigate the effects of the association spironolactone (25 mg)/altizide (15 mg) as monotherapy on left ventricular hypertrophy (LVH) in patients with mild to moderate hypertension."	9.08	Effects of spironolactone-altizide on left ventricular hypertrophy. ( Brohet, C; Cosyns, J; Degre, S; Detry, JM; Kormoss, N; Unger, P, 1998)
"A large-scale, open, nonrandomized, multicenter, 90-day study of the safety and efficacy of a thiazide diuretic and aldosterone antagonist combination (Aldactazine, 25 mg spironolactone and 15 mg altizide, 1/day) as monotherapy was performed in 946 patients with mild to moderate hypertension (diastolic blood pressure [BP] between 90 and 120 mm Hg)."	9.06	Clinical update: spironolactone and altizide as monotherapy in systemic hypertension. ( Dueymes, JM, 1990)
"In a double-blind, randomized, multicenter study of 194 patients with moderate hypertension, spironolactone and nifedipine were found to reduce blood pressure (BP) to about the same extent and in the same percentage of patients after 45 days of treatment (47 and 50%, respectively)."	9.06	Spironolactone versus nifedipine in essential hypertension. ( Capron, MH; Henry, M; Pelletier, B; Wehrlen, M, 1990)
"The aim of this study was to compare the efficacy and safety of enalapril and a combination of a thiazide diuretic (altizide) and a diuretic that reduce potassium excretion (spironolactone), in patients presenting moderate essential hypertension."	9.06	[Efficacy and tolerability of enalapril compared to altizide combined with spironolactone in patients with moderate arterial hypertension]. ( Baudouy, M; Camous, JP; Durand, P; Gibelin, P; Morand, P, 1986)
"The effect of adding spironolactone (Aldactone) on muscle electrolytes was studied in 48 patients with arterial hypertension and/or congestive heart failure who had received conventional diuretic treatment, including a potassium supplement, for more than 1 year."	9.06	Effects of spironolactone on serum and muscle electrolytes in patients on long-term diuretic therapy for congestive heart failure and/or arterial hypertension. ( Dyckner, T; Wester, PO; Widman, L, 1986)
"We conducted a meta-analysis to summarize all available evidence from randomized controlled trial studies regarding the clinical efficacy and safety of spironolactone in patients with resistant hypertension (RH) and provided a quantitative assessment."	9.05	Clinical efficacy and safety of spironolactone in patients with resistant hypertension: A systematic review and meta-analysis. ( Chen, C; Li, D; Lin, Q; Zhou, K; Zhu, XY, 2020)
"Nineteen patients with uncomplicated essential hypertension and low activity of plasma renin in response to a change from recumbency to an upright posture along with furosemide administration were given spironolactone, 400 mg/d, or chlorthalidone, 100mg/d, in a double-blind, random-sequence, crossover trial."	9.05	Comparison of chlorthalidone and spironolactone in low--renin essential hypertension. ( Kreeft, JH; Larochelle, P; Ogilvie, RI, 1983)
"57 years), with primary arterial hypertension, was submitted to two periods of treatment in a cross-over study with spironolactone and potassium canrenoate."	9.05	[Clinical study of the efficacy of oral potassium canrenoate and spironolactone in essential arterial hypertension]. ( Fanti, P; Mantellini, R; Sciarra, F; Tosti-Croce, C, 1983)
"Once-a-day therapy with spironolactone has been compared with a twice-a-day regimen in an open crossover trial in patients with essential hypertension."	9.05	Comparison of a single-dose and twice-a-day spironolactone therapy in mild hypertension. ( Dynon, M; Louis, WJ; Ludbrook, A; Mendelsohn, FA, 1980)
"The effects of placebo and of a spironolactone-althiazide combination in the treatment of twenty-two Kenyan Africans with hypertension were assessed using a double-blind technique."	9.05	The use of a spironolactone and althiazide combination (aldactacine) in the treatment of benign essential hypertension. ( Mngola, EN, 1980)
"The blood pressure lowering effects of spironolactone have been studied in 40 subjects with benign essential hypertension in an attempt to determine the optimum starting dose for the drug."	9.04	[Detection of the optimal dose of spironolactone for the treatment of benign essential hypertension]. ( Rhomberg, F, 1977)
"In a single blind crossover trial, spironolactone (50 mg twice a day), and hydrochlorothiazide (50 mg twice a day) were equally effective hypotensive agents in 16 patients with untreated essential hypertension."	9.04	A comparison between spironolactone and hydrochlorothiazide with and without alpha-methyldopa in the treatment of hypertension. ( Friedman, A; Johnston, CI; Suthers, MB; Walter, NM, 1978)
"A double-blind study of hydrochlorothiazide and spironolactone, alone and in combination, was conducted in 49 patients with mild-to-moderate essential hypertension after a 4-wk placebo washout period."	9.04	Hydrochlorothiazide and spironolactone in hypertension. ( Schrijver, G; Weinberger, MH, 1979)
"In 61 out-patients with essential hypertension, grade I or II, propranolol was administered alone in increasing doses (3 x 40 mg/d or 3 x 80 mg/d) or, if there was insufficient response, with a double or triple combination consisting additionally of spironolactone (50 mg/d)-thiabutazide (5 mg/d) and dihydralazine (3 x 25 mg/d)."	9.04	[Treatment of essential hypertension with a combination of propranolol, spironolactone-thiabutazide and dihydralazine (author's transl)]. ( Ebel, H; Klaus, D; Lübke, H; Witzgall, H; Zehner, J, 1978)
"In a crossover study 32 patients with hypertension were randomly allocated to treatment with spironolactone 200 mg/day for two months, propranolol 320 mg/day for two months, and a combination of both drugs at half the dose."	9.04	Renin concentrations and effects of propranolol and spironolactone in patients with hypertension. ( Kågedal, B; Karlberg, BE; Tegler, L; Tolagen, K, 1976)
"The effect of a six-week course of spironolactone 300 mg/day was examined in 25 unselected patients with essential hypertension."	9.04	Spironolactone in essential hypertension: evidence against its effect through mineralocorticoid antagonism. ( Edmonds, CJ; Hoffbrand, BI; Smith, T, 1976)
"35 patients with benign essential hypertension were treated for 6 weeks with high doses of the mineralocorticoid-antagonist spironolactone (400 mg/day), or with the "loop-diuretic" mefruside (mean maximal dose 110 mg/day)."	9.04	[Correlations between blood pressure, blood volume and plasma renin during therapy with diuretics in essential hypertension. Comparison between the mineralocorticoid antagonist spironolactone and the "loop" diuretic mefruside]. ( Beretta-Piccoli, C; de Châtel, R; Hirsch, D; Reubi, FC; Weidmann, P, 1977)
"The effect on BP of 100 and 200 mg spironolactone/day has been compared with that of methyl-dopa, 750 mg/day, and with combined treatment with both drugs in 32 patients with essential hypertension."	9.04	The effect of spironolactone (Aldactone) and methyldopa in low and normal renin hypertension. ( Giezendanner, L; Solheim, SB; Sundsfjord, JA, 1975)
"To review comparative efficacy and tolerability data between the two main mineralocorticoid receptor antagonists (MRAs), spironolactone and eplerenone, in patients with resistant hypertension (HTN)."	9.01	Eplerenone Versus Spironolactone in Resistant Hypertension: an Efficacy and/or Cost or Just a Men's Issue? ( Manolis, AA; Manolis, AS; Manolis, TA; Melita, H, 2019)
"This study was designed to assess the effect of additional spironolactone on blood pressure in patients with resistant hypertension."	8.95	Addition of spironolactone in patients with resistant hypertension: A meta-analysis of randomized controlled trials. ( Ju, Y; Liu, L; Xu, B, 2017)
"The efficacy of add-on use of spironolactone in patients with resistant hypertension has been investigated in several small studies."	8.95	A meta-analysis of add-on use of spironolactone in patients with resistant hypertension. ( Dong, P; Liu, H; Zhao, D; Zhao, J, 2017)
"To assess the effects of eplerenone monotherapy versus placebo for primary hypertension in adults."	8.95	Eplerenone for hypertension. ( Kinkade, A; Masson, SC; Stabler, SN; Tam, TS; Tejani, AM; Tsang, MP; Tung, A; Wu, MH, 2017)
"The role of eplerenone in arterial hypertension has been investigated only in small studies."	8.90	Efficacy and safety of eplerenone in the management of mild to moderate arterial hypertension: systematic review and meta-analysis. ( Gaudio, C; Greco, C; Patti, G; Pelliccia, F; Rosano, G, 2014)
"(2) In RALES, low-dose spironolactone in addition to standard of care, produced a 30% improvement in survival in progressive heart failure, commonly assumed to reflect deleterious effects of aldosterone, with spironolactone competing with aldosterone for cardiac mineralocorticoid receptors."	8.86	Aldosterone, hypertension and heart failure: insights from clinical trials. ( Funder, JW, 2010)
"Spironolactone is an aldosterone antagonist, considered fourth line therapy for hypertension in patients already treated with multiple medications."	8.86	Spironolactone for hypertension. ( Batterink, J; Fowkes, CT; Stabler, SN; Tejani, AM, 2010)
"To review the pharmacology, pharmacokinetics, pharmacodynamics, efficacy data, and adverse effects of spironolactone in the treatment of resistant hypertension."	8.86	Spironolactone management of resistant hypertension. ( Marrs, JC, 2010)
" A newer agent, eplerenone, has been recently licensed for the treatment of heart failure and in the US also for hypertension."	8.84	Evaluation of the aldosterone-blocking agent eplerenone in hypertension and heart failure. ( George, J; Struthers, AD, 2007)
"Eplerenone is a selective aldosterone blocker (SAB) approved for the treatment of essential hypertension."	8.82	Eplerenone: a review of its use in essential hypertension. ( Croom, KF; Perry, CM, 2005)
"Nebivolol is an eﬀective treatment option for resistant hypertension and the antihypertensive eﬀect of nebivolol is similar to low-dose spironolactone."	8.31	Antihypertensive Efficacy Of Nebivolol And Low Dose Spironolactone In Patients With Resistant Hypertension. ( Avcı, Y; Bıyık, İ; Çizgici, AY; Demir, AR; Özal, E; Püşüroğlu, H, 2023)
"The aim of this study was to determine whether arterial stiffness assessed with the biochemical parameter active matrix metalloproteinase (MMP)-9 and the clinical parameters pulse pressure (PP) and pulse wave velocity predicts the response to spironolactone in resistant hypertension (RH)."	8.12	Prediction of the early response to spironolactone in resistant hypertension by the combination of matrix metalloproteinase-9 activity and arterial stiffness parameters. ( Aceves-Ripoll, J; Alvarez-Llamas, G; Baldan-Martin, M; Barderas, MG; de la Cuesta, F; González-Lafuente, L; Navarro-García, JA; Rodríguez-Sánchez, E; Ruilope, LM; Ruiz-Hurtado, G; Segura, J, 2022)
"Identify blood pressure (BP) response to spironolactone in patients with apparent therapy-resistant hypertension (aTRH) using electronic medical records (EMRs) in order to estimate response in a real-world clinical setting."	7.96	Retrospective cohort study to characterise the blood pressure response to spironolactone in patients with apparent therapy-resistant hypertension using electronic medical record data. ( Brown, N; Luther, JM; Nian, H; Perkins, B; Shuey, M; Yu, C, 2020)
"In the PATHWAY-2 study of resistant hypertension, spironolactone reduced blood pressure substantially more than conventional antihypertensive drugs."	7.88	Endocrine and haemodynamic changes in resistant hypertension, and blood pressure responses to spironolactone or amiloride: the PATHWAY-2 mechanisms substudies. ( Brown, MJ; Caulfield, MJ; Cruickshank, JK; Ford, I; MacDonald, TM; Mackenzie, IS; McInnes, GT; Morant, SV; Padmanabhan, S; Salsbury, J; Sever, P; Webb, DJ; Williams, B, 2018)
"Cross-sectional data of the single-center "Eplerenone in Primary Hyperparathyroidism" trial were used."	7.83	Parathyroid hormone, aldosterone-to-renin ratio and fibroblast growth factor-23 as determinants of nocturnal blood pressure in primary hyperparathyroidism: the eplerenone in primary hyperparathyroidism trial. ( Belyavskiy, E; Brandenburg, VM; Brussee, H; Catena, C; Fahrleitner-Pammer, A; Gaksch, M; Grübler, MR; März, W; Meinitzer, A; Perl, S; Pieske, B; Pilz, S; Scharnagl, H; Sechi, LA; Tomaschitz, A; Van Ballegooijen, AJ; Verheyen, N; Wetzel, J, 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."	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)
"MBG-induced vascular fibrosis is a likely target for spironolactone."	7.81	Marinobufagenin-induced vascular fibrosis is a likely target for mineralocorticoid antagonists. ( Bagrov, AY; Bagrov, KA; Emelianov, IV; Fedorova, OV; Frolova, EV; Grigorova, YN; Juhasz, O; Konradi, AO; Lakatta, EG; Marshall, CA; Wei, W, 2015)
"Early spironolactone treatment decreases heart failure development frequency by improving myocardial systolic and diastolic function and attenuating hypertrophy and fibrosis in spontaneously hypertensive rats."	7.81	Early Spironolactone Treatment Attenuates Heart Failure Development by Improving Myocardial Function and Reducing Fibrosis in Spontaneously Hypertensive Rats. ( Blotta, DA; Bonomo, C; Campos, DH; Cezar, MD; Cicogna, AC; Damatto, RL; Gomes, MJ; Lima, AR; Martinez, PF; Okoshi, K; Okoshi, MP; Oliveira, SA; Pagan, LU; Rosa, CM, 2015)
"Spironolactone attenuates interstitial fibrosis and cardiomyocyte hypertrophy in hypertensive heart disease."	7.80	Cardiac magnetic resonance assessment of interstitial myocardial fibrosis and cardiomyocyte hypertrophy in hypertensive mice treated with spironolactone. ( Coelho-Filho, OR; Jerosch-Herold, M; Kwong, R; Mitchell, R; Moreno, H; Neilan, TG; Shah, RV, 2014)
"A chronic increase in circulating angiotensin II (Ang II) activates an aldosterone-mineralocorticoid receptor-ouabain neuromodulatory pathway in the brain that increases neuronal activation in hypothalamic nuclei, such as the paraventricular nucleus (PVN) and causes progressive hypertension."	7.79	Central mineralocorticoid receptors and the role of angiotensin II and glutamate in the paraventricular nucleus of rats with angiotensin II-induced hypertension. ( Gabor, A; Leenen, FH, 2013)
"Aim of the study is to evaluate the impact of spironolactone (SPL) on indexes of metabolic syndrome (MS) and further investigate the mechanisms underlying its protective effects."	7.79	Spironolactone prevents dietary-induced metabolic syndrome by inhibiting PI3-K/Akt and p38MAPK signaling pathways. ( Liang, LY; Lin, YE; Liu, MJ; Long, HD; Zeng, ZH, 2013)
"Circulating angiotensin II (Ang II) activates a central aldosterone-mineralocorticoid receptor neuromodulatory pathway, which mediates most of the Ang II-induced hypertension."	7.79	Role of brain corticosterone and aldosterone in central angiotensin II-induced hypertension. ( Ahmad, M; Huang, BS; Leenen, FH; White, RA, 2013)
"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)
"Add-on therapy with eplerenone effectively lowers BP in patients with difficult-to-treat primary hypertension."	7.79	Determinants of blood pressure reduction by eplerenone in uncontrolled hypertension. ( Arnoldus, JH; Danser, AH; de Bruijne, EL; Deinum, J; Frenkel, WJ; Jansen, PM; Kerstens, MN; van den Born, BJ; van den Meiracker, AH; Wijbenga, JA; Woittiez, AJ; Zietse, R, 2013)
" In the present study, we investigated the contribution of aldosterone to the renal p21 expression and senescence during the development of angiotensin II (AngII)-induced hypertension."	7.78	Aldosterone does not contribute to renal p21 expression during the development of angiotensin II-induced hypertension in mice. ( Deguchi, K; Hitomi, H; Kitada, K; Kobori, H; Lei, B; Masaki, T; Minamino, T; Mori, H; Nakano, D; Nishiyama, A, 2012)
"The aim of this paper is to report a case of unilateral PA with spontaneous remission and reduction of cardiac hypertrophy after long-term spironolactone (SP) therapy."	7.78	Unilateral primary aldosteronism with spontaneous remission after long-term spironolactone therapy. ( Demura, M; Karashima, S; Kometani, M; Takata, H; Takeda, Y; Yamagishi, M; Yoneda, T, 2012)
"To investigate whether exposure to spironolactone treatment affects the risk of incident breast cancer in women over 55 years of age."	7.78	Spironolactone and risk of incident breast cancer in women older than 55 years: retrospective, matched cohort study. ( Macdonald, TM; Mackenzie, IS; Morant, S; Thompson, A; Wei, L, 2012)
"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)
" It has been reported that eplerenone has a potential antihypertensive effect, with a profile slightly different from that of spironolactone, and has fewer adverse reactions, suggesting that it may become a first-line treatment for hypertension."	7.76	Clinical effects of eplerenone, a selective aldosterone blocker, in Japanese patients with essential hypertension. ( Fukuda, S; Sato, A, 2010)
" The addition of spironolactone to her previous medications controlled and normalized hypertension, hypokalemia, and hormonal abnormalities within 4 months."	7.76	Resistant hypertension in an aged woman presenting with clinical features simulating ectopic ACTH syndrome--response to spironolactone--. ( Harada, E; Mizuno, Y; Morikawa, Y; Nakagawa, H; Saito, Y; Semba, F; Yasue, H; Yoshimura, M, 2010)
"The aim of this study was to evaluate the use of spironolactone and doxazosin as treatment for patients with resistant hypertension."	7.75	Spironolactone and doxazosin treatment in patients with resistant hypertension. ( Baldó, E; Costa, JA; González, C; Pascual, JM; Pérez-Lahiguera, F; Rodilla, E, 2009)
" To elucidate the potential role of local renin-angiotensin system in aldosterone-induced cardiovascular injury, we investigated the effects of selective mineralocorticoid receptor (MR) antagonist eplerenone (EPL), angiotensin (Ang) II type 1 receptor antagonist candesartan (ARB), and superoxide dismutase mimetic tempol (TEM) on the development of hypertension, vascular injury, oxidative stress, and inflammatory-related gene expression in aldosterone-treated hypertensive rats."	7.74	Angiotensin II receptor type 1-mediated vascular oxidative stress and proinflammatory gene expression in aldosterone-induced hypertension: the possible role of local renin-angiotensin system. ( Hirata, Y; Hirono, Y; Kobayashi, N; Sakurada, M; Shichiri, M; Sugiyama, T; Suzuki, N; Takai, S; Yoshimoto, T, 2007)
" Spironolactone, a mineralocorticoid receptor antagonist, decreases ischemic cerebral infarct size in male spontaneously hypertensive stroke-prone rats (SHRSP)."	7.74	Spironolactone improves structure and increases tone in the cerebral vasculature of male spontaneously hypertensive stroke-prone rats. ( Dorrance, AM; Pollock, DM; Rigsby, CS, 2007)
"We have conducted an open observational study of the use of spironolactone 25-50 mg in the management of patients with resistant hypertension."	7.74	Low-dose spironolactone in the management of resistant hypertension: a surveillance study. ( Beevers, DG; Lane, DA; Shah, S, 2007)
" To elucidate its significance for myocardial fibrosis in the hypertensive heart, we used a mouse model with infusion of angiotensin II and examined results by histology, immunohistochemistry, in situ hybridization, and quantitative real-time reverse transcriptase polymerase chain reaction (RT-PCR)."	7.74	Eplerenone attenuates myocardial fibrosis in the angiotensin II-induced hypertensive mouse: involvement of tenascin-C induced by aldosterone-mediated inflammation. ( Hiroe, M; Imanaka-Yoshida, K; Inada, H; Nishioka, T; Onishi, K; Suzuki, M; Takakura, N; Yoshida, T, 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)
"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)
"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)
"We describe a hypertensive nephrosclerosis patient presenting with severe hyperkalemia due to a combination therapy of the angiotensin receptor blocker (ARB) candesartan and spironolactone despite mildly decreased renal function."	7.73	Life-threatening hyperkalemia during a combined therapy with the angiotensin receptor blocker candesartan and spironolactone. ( Fujii, H; Inenaga, T; Kawano, Y; Nakahama, H; Nakamura, S; Yoshihara, F, 2005)
"To compare efficacy of use of the blocker of aldosteron receptors spironolactone and diuretic indapamide in low-renin arterial hypertension (AH), their action on blood pressure, serum concentrations of sodium, potassium, creatinine, plasmic renin activity (PRA), plasmic aldosteron concentration (PAC)."	7.73	[Use of spironolactone and indapamide in the treatment of low-renin arterial hypertension]. ( Bagdonas, G; Kazanavichus, G; Naudzhunas, A; Yankauskene, L, 2006)
" Since chronic inhibition of nitric oxide (NO) synthase with N(omega)-nitro-L-arginine methyl ester (L-NAME) induces systemic hypertension associated with cardiovascular inflammation and remodeling, we examined the potential role of aldosterone in this process using eplerenone, a selective aldosterone receptor antagonist."	7.73	The antagonism of aldosterone receptor prevents the development of hypertensive heart failure induced by chronic inhibition of nitric oxide synthesis in rats. ( Asano, Y; Fujita, M; Hirata, A; Hori, M; Kitakaze, M; Minamino, T; Okada, K; Sanada, S; Shintani, Y; Takashima, S; Tomoike, H; Tsukamoto, O; Yamasaki, S; Yulin, L, 2006)
"We report the case of normoaldosterone spironolactone sensitive hypertension."	7.73	[Normoaldosterone spironolactone sensitive hypertension--a case report]. ( Herman, ZS; Krysiak, R; Okopień, B, 2005)
"We report the case of normoaldosterone spironolactone sensitive hypertension."	7.73	[Normoaldosterone spironolactone sensitive hypertension]. ( Herman, ZS; Krysiak, R; Okopień, B, 2006)
"The effects of low-dose oral spironolactone (SPIRO) in a rat model of hypertensive heart failure (spontaneously hypertensive heart failure rat) were compared with its effects when combined with captopril (CAP)."	7.72	Combined effects of low-dose oral spironolactone and captopril therapy in a rat model of spontaneous hypertension and heart failure. ( Bauer, JA; Ghosh, S; Holycross, BJ; Kambara, A; Kwiatkowski, P; McCune, SA; Schanbacher, B; Wung, P, 2003)
"Aldosterone-induced hypertension is associated with renal damage that may be mediated by endothelin-1 (ET-1)."	7.71	Contribution of endothelin-1 to renal activator protein-1 activation and macrophage infiltration in aldosterone-induced hypertension. ( Chen, X; He, G; Schiffrin, EL; Tostes, RC; Touyz, RM, 2002)
"The role of spironolactone as pemphigoid-inducing agent has recently been suggested."	7.71	[Bullous pemphigoid induced by spironolactone]. ( Cordel, N; Courville, P; Gilbert, D; Joly, P; Lauret, P; Modeste, AB, 2002)
"Spironolactone is a safe, effective therapy for patients with refractory hypertension."	7.71	The role of spironolactone in the treatment of patients with refractory hypertension. ( Carré, E; Lincoff, AM; Mertes, M; Ouzan, J; Pérault, C, 2002)
" The antistroke effects of captopril treatment occurred without an antihypertensive effect, weren't altered by enhancing hypertension during treatment (with dexamethasone), and couldn't be duplicated by antihypertensive treatment with hydralazine."	7.70	Effect of poststroke captopril treatment on mortality associated with hemorrhagic stroke in stroke-prone rats. ( King, SR; Smeda, J; Vasdev, S, 1999)
"A case of primary aldosteronism is presented in which the CT scan was initially misleading, adrenocortical scintigraphy was rendered inaccurate by pharmacological interference of spironolactone, and selective adrenal venous sampling of aldosterone was technically difficult."	7.69	Interference by spironolactone on adrenocortical scintigraphy and other pitfalls in the location of adrenal abnormalities in primary aldosteronism. ( Freitas, JE; Grekin, R; Gross, MD; Shapiro, B, 1994)
"A case of primary aldosteronism treated with spironolactone therapy has been followed up for 24 years."	7.68	Twenty-four year spironolactone therapy in an aged patient with aldosterone-producing adenoma. ( Hashimoto, T; Ito, Y; Koshida, H; Miyamori, I; Morimoto, S; Morise, T; Takeda, R; Yamazaki, T, 1992)
"The effects of the mineralocorticoid antagonist mespirenone on the development and maintenance of aldosterone-induced hypertension in Sprague-Dawley rats has been studied."	7.68	Effect of a new mineralocorticoid antagonist mespirenone on aldosterone-induced hypertension. ( Agarwal, M; Kalimi, M; Opoku, J; Qureshi, D, 1991)
"The long-term efficacy and tolerance of spironolactone in essential hypertension was evaluated among 20,812 patients referred to the Broussais and St."	7.67	Efficacy and tolerance of spironolactone in essential hypertension. ( Charru, A; Chatellier, G; Corvol, P; DeVries, C; Jeunemaitre, X; Kreft-Jais, C; Menard, J; Plouin, PF, 1987)
"To evaluate the role of the renin-angiotensin system and sodium depletion in the hypotensive response to 1-sarcosine-8-alanine-angiotensin II (saralasin), 15 male patients with essential hypertension were studied on a diet containing 120 mEq of sodium and 100 mEq of potassium per day."	7.66	Angiotensin II, plasma renin and sodium depletion as determinants of blood pressure response to saralasin in essential hypertension. ( Barrett, JD; Eggena, P; Golub, MS; Sambhi, MP; Thananopavarn, C, 1980)
"Spironolactone alone in full dosage failed to correct hypertension in a patient with Conn's syndrome and renal impairment, although the previously increased total exchangeable sodium fell to normal and the previously suppressed plasma angiotensin II did not rise above the normal range."	7.66	Combined captopril and spironolactone treatment in Conn's syndrome with renal impairment and refractory hypertension. ( Atkinson, AB; Brown, JJ; Davies, DL; Lever, AF; Robertson, JI, 1981)
"A 38-year-old woman with hypercalcemia, severe hypertension, and high renin levels was treated with the angiotensin-converting enzyme inhibitor captopril."	7.66	Hypertension in a patient with hypercalcemia: captopril and verapamil. ( Brunner, HR; Burckhardt, P; Gavras, H; Waeber, B, 1982)
"Intrarenal handling of uric acid was studied in 12 patients with essential hypertension under spironolactone treatment (200 mg/day)."	7.66	Changes in intrarenal uric acid handling during chronic spironolactone treatment in patients with essential hypertension. ( Boer, P; Dorhout Mees, EJ; Peuker, KH; Roos, JC, 1982)
"In view of recent evidence that spironolactone may inhibit synthesis of corticosteroids by a direct effect on the adrenal cortex, adrenocortical function was studied in eight patients with essential hypertension who had been treated with spironolactone from 3 months to 14 years."	7.66	Long term spironolactone and the adrenal cortex in essential hypertension. ( Gorchein, A; Horth, CE; James, VH; Lewis, PS; May, CN, 1980)
"Marked improvement in the severe hypertension (250/150 mmHg) and hirsutism of a patient suffering from polycystic ovary syndrome was quickly achieved by the use of spironolactone 200 mg per day."	7.66	Successful treatment of polycystic ovary syndrome with spironolactone or bromocriptine. ( Blum, I; Chovers, I; Kaufman, H; Marilus, R; Rusecki, Y, 1981)
") before and during treatment with spironolactone (Sp, 75--100 mg/day) for at least 8 months was studied in 11 patients with essential hypertension."	7.66	Reduced response of plasma aldosterone to acute ACTH stimulation during long-term treatment with spironolactone in essential hypertension. ( Kim, KS; Miyamori, I; Miyamoto, M; Morimoto, S; Takeda, R; Uchida, K, 1979)
"To determine the effect of aldosterone antagonist on renal prostaglandin E synthesis, the rate of urinary excretion of immunoreactive prostaglandin E was measured radioimmunologically before and during the oral administration of an aldosterone antagonist, spironolactone, in 5 patients with essential hypertension, 3 with primary aldosteronism and 2 with postoperative primary aldosteronism."	7.66	Effect of spironolactone on urinary excretion of immunoreactive prostaglandin E in essential hypertension and primary aldosteronism. ( Abe, K; Chiba, S; Irokawa, N; Otsuka, Y; Sakurai, Y; Sato, M; Seino, M; Yasujima, M; Yoshinaga, K, 1978)
"The antihypertensive effect of spironolactone was studied in 20 patients with essential hypertension and normal stimulated peripheral renin activity (PRA)."	7.66	Antihypertensive responses to spironolactone in normal renin hypertension. ( Ogilvie, RI; Piafsky, KM; Ruedy, J, 1978)
"In order to evaluate the relationship between aldosterone status and the blood pressure-lowering effect of spironolactone, 38 patients with essential hypertension were treated with spironolactone (400 mg/day) during one week in hospital on a rigidly sodium-restricted diet."	7.66	Role of aldosterone in the antihypertensive effect of spironolactone in essential hypertension. ( Benraad, H; Benraad, T; Drayer, J; Hoefnagels, W; Kloppenborg, P, 1978)
"The hypotensive effect of spironolactone and its relation to the changer in volaemia and renin activity induced by the drug were studied in 12 hospitalised patients with essential hypertension."	7.65	[Relations between hypotensive effect and modifications of volemia and plasma renin activity in patients with essential hypertension treated using spironolactone]. ( Corgnati, A; Palù, CD; Pessina, AC, 1977)
"Urinary kallikrein excretion was measured before and after administration of spironolactone in 12 patients with essential hypertension (including 7 patients with low renin and 5 patients with normal renin) and 6 patients with primary aldosteronism."	7.65	Effect of spironolactone on urinary kallikrein excretion in patients with essential hypertension and in primary aldosteronism. ( Abe, K; Chiba, S; Irokawa, N; Otsuka, Y; Sakurai, Y; Seino, M; Yasujima, M; Yoshinaga, K, 1977)
" Six of these patients were treated with spironolactone and developed gynecomastia."	7.65	Pathophysiology of spironolactone-induced gynecomastia. ( Kisch, ES; Newmark, SR; Rose, LI; Underwood, RH; Williams, GH, 1977)
"The antihypertensive effect and the tolerance of the association of spironolactone and chlorthalidone were evaluated clinically and by numerous laboratory examinations in a group of 18 patients affected with non-complicated essential hypertension."	7.65	[Spironolactone combined with chlorthalidone in the treatment of essential arterial hypertension]. ( Favilli, R; Gragnoli, G; Nami, R; Puccetti, F; Tanganelli, I, 1975)
"The anti-hypertensive effect of spironolactone and thiabutazide was tested on 47 unselected patients with primary hypertension."	7.65	[Spironolactone and thiabutazide in the treatment of essential hypertension (author's transl)]. ( Braun, B; Klaus, D; Klump, F; Lemke, R; Zehner, J; Zöfel, P, 1975)
"The effect of prolonged preoperative treatment with spironolactone has been studied in a series of 67 patients with hypertension, aldosterone excess, and low plasma renin."	7.65	Comparison of surgery and prolonged spironolactone therapy in patients with hypertension, aldosterone excess, and low plasma renin. ( Brown, JJ; Davies, DL; Ferriss, JB; Fraser, R; Haywood, E; Lever, AF; Robertson, JI, 1972)
" of spironolactone (SL) in 48 patients with essential hypertension."	7.65	Treatment of hypertension with hydrochlorothiazide and spironolactone. ( Ogilvie, RI; Ruedy, J, 1969)
"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)
"We considered that RSD could reduce the recurrence of AF in patients with CKD by modulating sympathetic hyperactivity."	6.87	Pulmonary vein isolation combined with spironolactone or renal sympathetic denervation in patients with chronic kidney disease, uncontrolled hypertension, paroxysmal atrial fibrillation, and a pacemaker. ( Chen, S; Hoye, NA; Kiuchi, MG; Pürerfellner, H, 2018)
"Spironolactone was more effective than SRD in reducing daytime systolic (P = 0."	6.84	Renal Denervation vs. Spironolactone in Resistant Hypertension: Effects on Circadian Patterns and Blood Pressure Variability. ( Armario, P; Barrera, Á; de la Sierra, A; Oliveras, A; Pareja, J; Pascual, J; Sans, L; Vázquez, S; Yun, S, 2017)
"Aldosterone excretion was determined by 24 h urine (24h-UAldo) collected at randomization and after 6 months of follow-up."	6.84	Effects of continuous positive airway pressure treatment on aldosterone excretion in patients with obstructive sleep apnoea and resistant hypertension: a randomized controlled trial. ( Cavalcanti, AH; Cortez, AF; de Souza, F; Margallo, V; Muxfeldt, ES; Salles, GF, 2017)
"INTRODUCTION Obstructive sleep apnea (OSA) is considered to be one of the major causes of resistant arterial hypertension (RAH)."	6.82	Effect of eplerenone on the severity of obstructive sleep apnea and arterial stiffness in patients with resistant arterial hypertension. ( Cofta, S; Krasińska, B; Krasiński, Z; Miazga, A; Pawlaczyk-Gabriel, K; Szczepaniak-Chicheł, L; Trafas, T; Tykarski, A, 2016)
"Eplerenone is a selective mineralocorticoid receptor antagonist; however, little is known about its effects on insulin action."	6.79	Effect of eplerenone on insulin action in essential hypertension: a randomised, controlled, crossover study. ( Atkinson, AB; Bell, PM; Ennis, C; Hunter, SJ; McMurray, EM; Wallace, IR, 2014)
"Amiloride (5 mg/d) was added to previous triple antihypertensive treatment (including a diuretic and an inhibitor of the renin-angiotensin-aldosterone system) and increased to 10 mg if BP control was not achieved at 4 weeks."	6.79	Amiloride lowers blood pressure and attenuates urine plasminogen activation in patients with treatment-resistant hypertension. ( Buhl, KB; Gram, J; Hansen, MR; Henriksen, JE; Jacobsen, IA; Jensen, BL; Oxlund, CS; Schousboe, K; Tarnow, L, 2014)
"Aldosterone breakthrough was observed in 22 of the subjects (55%)."	6.78	Effect of aldosterone breakthrough on albuminuria during treatment with a direct renin inhibitor and combined effect with a mineralocorticoid receptor antagonist. ( Fukuda, S; Sato, A, 2013)
"Hypertension is associated with endothelial dysfunction and activated Rho-associated kinases (ROCKs)."	6.77	Mineralocorticoid receptor blocker eplerenone improves endothelial function and inhibits Rho-associated kinase activity in patients with hypertension. ( Chayama, K; Fujii, Y; Fujimura, N; Hata, T; Hidaka, T; Higashi, Y; Idei, N; Iwamoto, Y; Kato, H; Kihara, Y; Liao, JK; Maruhashi, T; Mikami, S; Noma, K; Soga, J, 2012)
"Amiloride 40 mg was as effective as the other diuretics."	6.73	The spironolactone, amiloride, losartan, and thiazide (SALT) double-blind crossover trial in patients with low-renin hypertension and elevated aldosterone-renin ratio. ( Ashby, MJ; Brown, MJ; Hood, SJ; Taylor, KP, 2007)
"Aldosterone antagonism has BP-independent effects on arterial stiffness."	6.71	Aldosterone-to-renin ratio, arterial stiffness, and the response to aldosterone antagonism in essential hypertension. ( Feely, J; Mahmud, A, 2005)
"6%), and a low rate of adverse effects."	6.67	Aldactazine/captopril combination, safe and effective in mild to moderate systemic hypertension: report on a multicenter study of 967 patients. ( Capron, MH; Pelletier, B; Schohn, DC; Spiesser, R; Wehrlen, M, 1990)
"Aspirin has been shown to acutely block the natriuretic effect of spironolactone in the mineralocorticoid-treated normal rat, dog, and man."	6.64	Failure of aspirin to antagonize the antihypertensive effect of spironolactone in low-renin hypertension. ( Hollifield, JW, 1976)
"Oxprenolol was the best tolerated drug, with only 5% of patients withdrawing due to side-effects compared to 13% on spironolacone and 29% on methyldopa."	6.64	Renin unresponsiveness and the effects of oxprenolol, methyldopa and spironolactone in pateints with essential hypertension. ( Beilin, LJ; Ledingham, JG; Thomas, GW; Yeates, KM, 1976)
"Treatment with propranolol resulted in marked suppression of the plasma renin activity (1."	6.64	Intrapatient comparison of treatment with chlorthalidone, spironolactone and propranolol in normoreninemic essential hypertension. ( Benraad, TJ; Drayer, JI; Festen, J; Kloppenborg, PW; van't Laar, A, 1975)
" Randomised controlled trials investigating the effect of additional spironolactone on office blood pressure (BP), ambulatory BP or adverse events in RH patients were included for analysis."	6.53	Efficacy and Safety of Spironolactone in Patients with Resistant Hypertension: A Meta-analysis of Randomised Controlled Trials. ( Huang, J; Wang, C; Xiong, B, 2016)
"Resistant hypertension is a common clinical situation."	6.53	Should All Patients with Resistant Hypertension Receive Spironolactone? ( Holaj, R; Petrák, O; Rosa, J; Štrauch, B; Widimský, J; Zelinka, T, 2016)
"A close association exists between hyperaldosteronism, RHTN, and obstructive sleep apnea (OSA) based upon recent studies which indicate that OSA is worsened by aldosterone-mediated fluid retention."	6.48	Resistant hypertension and aldosterone: an update. ( Ahmed, MI; Calhoun, DA; Clark, D, 2012)
"Aldosterone was in the past considered only as a prohypertensinogenic agent."	6.46	Aldosterone in uremia - beyond blood pressure. ( Koleganova, N; Ritz, E, 2010)
"Eplerenone has been reported to have anti-hypertensive and protective effects on cardiovascular and renal injury in salt-sensitive hypertensive animal models, such as the Dahl salt-sensitive (DS) hypertensive rat and leptin receptor-deficient spontaneously hypertensive rat (SHR/cp)."	6.45	Effects of eplerenone, a selective mineralocorticoid receptor antagonist, on clinical and experimental salt-sensitive hypertension. ( Takeda, Y, 2009)
"Features of visceral obesity and obstructive sleep apnea that may stimulate aldosterone secretion are described here."	6.44	Obesity, sleep apnea, aldosterone, and hypertension. ( Goodfriend, TL, 2008)
"Aldosterone is an important mediator in the pathogenesis of heart failure, and increased plasma aldosterone levels are associated with a poor prognosis."	6.44	Drug insight: aldosterone-receptor antagonists in heart failure--the journey continues. ( Francis, GS; Kalidindi, SR; Tang, WH, 2007)
"Aldosterone is an important and independent target for therapeutic intervention in hypertension and hypertension-related diseases."	6.42	Aldosterone receptor antagonists for hypertension: what do they offer? ( Krum, H; Liew, D, 2003)
"Eplerenone is a newer aldosterone antagonist that is much more selective, with minimal affinity for progesterone and androgenic receptors; therefore, there are very few reports of adverse sexual effects."	6.42	Eplerenone in hypertension. ( Burgess, E, 2004)
"Aldosterone has been identified as a critically important neurohormone with direct detrimental effects on the myocardium."	6.41	Angiotensin receptor blockers and aldosterone antagonists in chronic heart failure. ( Miller, AB; Srivastava, P, 2001)
" The present study analyzes whether the mineralocorticoid receptor antagonist spironolactone ameliorates the dysbiosic state in a genetic model of neurogenic hypertension."	5.69	Mineralocorticoid receptor blockade improved gut microbiota dysbiosis by reducing gut sympathetic tone in spontaneously hypertensive rats. ( Duarte, J; Gómez-Guzmán, M; González-Correa, C; Jiménez, R; Martín-Morales, N; Miñano, S; Moleón, J; O'Valle, F; Robles-Vera, I; Romero, M; Sánchez, M; Toral, M, 2023)
"Increased fibrosis was accompanied by myofibroblast and macrophage infiltration in the heart and the kidney."	5.62	The effect of spironolactone on cardiac and renal fibrosis following myocardial infarction in established hypertension in the transgenic Cyp1a1Ren2 rat. ( Leader, CJ; Walker, RJ; Wilkins, GT, 2021)
"The mineralocorticoid receptor antagonist spironolactone lowers blood pressure in patients with resistant hypertension despite antihypertensive treatment with angiotensin-converting inhibitors (ACEi) and angiotensin-II receptor blockers (ARB)."	5.51	The mineralocorticoid receptor blocker spironolactone lowers plasma interferon-γ and interleukin-6 in patients with type 2 diabetes and treatment-resistant hypertension. ( Fonseca, MPD; Jacobsen, IA; Jensen, BL; Ketelhuth, DFJ; Oxlund, CS; Palarasah, Y; Stubbe, J; Svenningsen, P; Thangaraj, SS, 2022)
"Eplerenone treatment of patients with PA reduces blood pressure, increases serum potassium level, and improves vascular status."	5.43	Eplerenone improves carotid intima-media thickness (IMT) in patients with primary aldosteronism. ( Anzai, K; Kawate, H; Matsuda, Y; Matsuzaki, C; Nomura, M; Ohnaka, K; Sakamoto, R; Shibue, K; Takayanagi, R, 2016)
"Hypertension is often associated with metabolic syndrome (MetS), and serves as a risk factor of MetS and its complications."	5.43	Eplerenone restores 24-h blood pressure circadian rhythm and reduces advanced glycation end-products in rhesus macaques with spontaneous hypertensive metabolic syndrome. ( Ding, Y; Hou, N; Hu, X; Li, C; Liu, Y; Ma, D; Mao, J; Peng, Y; Shang, H; Sun, X; Wang, C; Wang, J; Xiao, RP; Xiao, Y; Zeng, F; Zhang, J; Zhang, X; Zhang, Y; Zheng, W, 2016)
"Primary aldosteronism (PA), the most common form of secondary hypertension, causes relevant morbidity."	5.43	The Clinical Value of Salivary Aldosterone in Diagnosis and Follow-Up of Primary Aldosteronism. ( Asbach, E; Bidlingmaier, M; Fourkiotis, V; Gerum, S; Lichtenauer, UD; Manolopoulou, J; Quinkler, M; Reincke, M, 2016)
"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)
"Aldosterone (Aldo) is an important active hormone in the renin-angiotensin-aldosterone system and plays a vital role in the development of hypertension, heart failure and other cardiovascular diseases."	5.38	Endogenous aldosterone is involved in vascular calcification in rat. ( Cai, Y; Jia, LX; Qi, YF; Tang, CS; Wang, X; Wu, SY; Xiao, CS; Yu, YR, 2012)
"Resistant hypertension has evolved as an important global health care problem."	5.37	What is the role of aldosterone excess in resistant hypertension and how should it be investigated and treated? ( Sica, DA, 2011)
" The cause of hyperkalemia was considered to be several doses of spiranolactone, an aldosterone antagonist, in addition to the long-term intake of ramipril, an ACE inhibitor."	5.36	Syncope caused by hyperkalemia during use of a combined therapy with the angiotensin-converting enzyme inhibitor and spironolactone. ( Erden, I; Ozhan, H; Yalcin, S, 2010)
"Aldosterone promotes renal fibrosis via the mineralocorticoid receptor (MR), thus contributing to hypertension-induced nephropathy."	5.35	Hypertension-induced renal fibrosis and spironolactone response vary by rat strain and mineralocorticoid receptor gene expression. ( Camp, JR; Cavallari, LH; Fashingbauer, LA; Geenen, DL; King, ST, 2008)
"Primary aldosteronism (PA) is the most common secondary cause of hypertension that has recently been implicated in alterations of the immune system and progression of cardiovascular disease."	5.35	Primary aldosteronism can alter peripheral levels of transforming growth factor beta and tumor necrosis factor alpha. ( Carvajal, CA; Castillo, CR; Contreras, FJ; Fardella, CE; Herrada, AA; Kalergis, AM; Mosso, LM; Stehr, CB, 2009)
"The hypertension was not different and virtually superimposable in WT vs."	5.35	The role of aldosterone in mediating the dependence of angiotensin hypertension on IL-6. ( Brands, MW; Cannon, JG; Schreihofer, DA; Sturgis, LC, 2009)
"The AMBER trial demonstrated that concomitant use of patiromer enabled the more persistent use of spironolactone by reducing the risk of hyperkalaemia in patients with resistant hypertension and advanced chronic kidney disease."	5.34	Patiromer versus placebo to enable spironolactone use in patients with resistant hypertension and chronic kidney disease (AMBER): results in the pre-specified subgroup with heart failure. ( Ackourey, G; Agarwal, R; Arthur, S; Mayo, MR; Rossignol, P; Warren, S; White, WB; Williams, B, 2020)
"Hyperkalemia is a complications of the use of angiotensin converting enzyme inhibitors, angiotensin receptor antagonists and aldosterone antagonists."	5.33	[Severe hyperkalemia associated to the use of losartan and spironolactone: case report]. ( Kauffmann, R; Orozco, R; Venegas, JC, 2005)
"Spironolactone is effective at reducing blood pressure in patients with uncontrolled resistant hypertension."	5.30	Patiromer versus placebo to enable spironolactone use in patients with resistant hypertension and chronic kidney disease (AMBER): a phase 2, randomised, double-blind, placebo-controlled trial. ( Agarwal, R; Garza, D; Ma, J; Mayo, MR; Romero, A; Rossignol, P; Warren, S; White, WB; Williams, B, 2019)
" We investigated changes in serum concentrations of the collagen synthesis biomarkers N-terminal propeptide of procollagen type III (PIIINP) (primary outcome) and C-terminal propeptide of procollagen type I (PICP) (secondary outcome) after non-randomised initiation of spironolactone as add-on therapy among patients with resistant hypertension enrolled in the 'Anglo-Scandinavian Cardiac Outcomes' trial (ASCOT)."	5.30	Potential spironolactone effects on collagen metabolism biomarkers in patients with uncontrolled blood pressure. ( Cleland, JG; Collier, T; Diez, J; Ferreira, JP; Girerd, N; Gonzalez, A; Huby, AC; López, B; Machu, JL; Pizard, A; Rossignol, P; Sattar, N; Sever, PS; Zannad, F, 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)
"Spironolactone treatment (50 mg/kg per day) for 7 days in deficient rats restored blood pressure and heart rate to normal levels and significantly reduced sodium levels in erythrocytes and cerebrospinal fluid."	5.29	Hypertension induced by a nonpressor dose of angiotensin II in kininogen-deficient rats. ( Katori, M; Kuribayashi, Y; Majima, M; Mizogami, S; Oh-ishi, S, 1994)
"Spironolactone, however, was able to prevent myocardial fibrosis in RHT and aldosterone models of acquired arterial hypertension irrespective of the development of LVH and the presence of hypertension."	5.29	Antifibrotic effects of spironolactone in preventing myocardial fibrosis in systemic arterial hypertension. ( Brilla, CG; Matsubara, LS; Weber, KT, 1993)
"We identified patients with RHTN, defined as baseline systolic blood pressure (SBP) between 140 and 160 mm Hg on 3 or more medications, in the Americas cohort of the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist trial, in which patients with HFpEF were randomized to spironolactone vs."	5.27	Spironolactone and Resistant Hypertension in Heart Failure With Preserved Ejection Fraction. ( Claggett, BL; Liu, J; Pitt, B; Rossignol, P; Solomon, S; Vardeny, O; Zannad, F, 2018)
"Renal denervation and spironolactone have both been proposed for the treatment of resistant hypertension, but their effects on preclinical target organ damage have not been compared."	5.27	Organ damage changes in patients with resistant hypertension randomized to renal denervation or spironolactone: The DENERVHTA (Denervación en Hipertensión Arterial) study. ( Armario, P; Clarà, A; de la Sierra, A; Molina, L; Oliveras, A; Pareja, J; Pascual, J; Sans, L; Vázquez, S, 2018)
"The mineralocorticoid receptor antagonist spironolactone significantly reduces albuminuria in patients with diabetes."	5.27	Predicting albuminuria response to spironolactone treatment with urinary proteomics in patients with type 2 diabetes and hypertension. ( Heerspink, HJL; Jacobsen, IA; Lindhardt, M; Mischak, H; Oxlund, C; Persson, F; Rossing, P; Zürbig, P, 2018)
"Spironolactone treatment normalized the arterial pressure in patients with primary aldosteronism at all Na intakes."	5.27	Effect of spironolactone on fluid volumes and adrenal steroids in primary aldosteronism. ( Hirano, Y; Ichikawa, S; Kogure, M; Matsuo, H; Murata, K; Sakamaki, T; Tajima, Y; Yagi, S, 1984)
"Treatment with spironolactone alone for 2 months corrected hypertension, hypokalemic alkalosis, and all laboratory and radiologic evidence of rickets and hyperparathyroidism, resulting in acceleration of growth rate."	5.27	Spironolactone-reversible rickets associated with 11 beta-hydroxysteroid dehydrogenase deficiency syndrome. ( Arnhold, IJ; Batista, MC; Bloise, W; Kater, CE; Mendonça, BB; Nicolau, W; Rocha, A, 1986)
"Spironolactone was prescribed at a mean dose of 98 mg, hydrochlorothiazide at 36 mg and cyclothiazide at 2 mg, during a mean follow-up of 20 months."	5.27	Long-term metabolic effects of spironolactone and thiazides combined with potassium-sparing agents for treatment of essential hypertension. ( Charru, A; Chatellier, G; Corvol, P; Degoulet, P; Jeunemaitre, X; Julien, J; Ménard, J; Plouin, PF, 1988)
" The data shows that this dosage of spironolactone gave minor adjustments of the systemic and renal circulation in spite of the consistent changes in BW, PV, PRA and PA."	5.26	Haemodynamic effects of treatment and withdrawal of spironolactone in essential hypertension. ( Falch, DK; Johansson, R; Norman, N; Odegaard, AE, 1979)
"Triamterene was administered in a dose of 100 mg/day for 8 days to 7 patients with essential hypertension."	5.26	Effect of triamterene on urinary excretion of immunoreactive prostaglandin E in essential hypertension. ( Abe, K; Chiba, S; Irokawa, N; Ito, T; Otsuka, Y; Saito, K; Sakurai, Y; Sato, M; Yasujima, M; Yoshinaga, K, 1979)
"Twenty patients suffering from primary hyperaldosteronism were studied."	5.26	[The renin-angiotensin-aldosterone system in hypertensive patients. II. Diagnosis of primary hyperaldosteronism]. ( Benguigui, L; Corvol, P; Houde, M; Menard, J; Milliez, P; Tonnelier, M, 1977)
"Eplerenone is reported to reduce the development of atrial fibrillation (AF)."	5.24	Eplerenone might affect atrial fibrosis in patients with hypertension. ( Fukunami, M; Furukawa, Y; Iwasaki, Y; Kawasaki, M; Kikuchi, A; Morita, T; Okuyama, Y; Sakata, Y; Tamaki, S; Yamada, T, 2017)
"This study investigated the effects and safety of eplerenone or thiazide diuretics in patients with hypertension and albuminuria (pretreatment urinary albumin/creatinine ratio ≥10 mg/gCr) treated with an angiotensin II receptor blocker."	5.24	Antialbuminuric effect of eplerenone in comparison to thiazide diuretics in patients with hypertension. ( Dohi, K; Fujimoto, N; Ichikawa, T; Isaka, N; Ito, M; Kitamura, T; Koyabu, S; Makino, K; Nakamura, M; Nishikawa, M; Ogura, T; Okamoto, S; Okubo, S; Sawai, T; Tamaru, S; Yamada, T, 2017)
"The randomized, multicentre study compared the efficacy of renal denervation (RDN) versus spironolactone addition in patients with true resistant hypertension."	5.24	Renal denervation in comparison with intensified pharmacotherapy in true resistant hypertension: 2-year outcomes of randomized PRAGUE-15 study. ( Bednář, F; Branny, M; Čurila, K; Holaj, R; Indra, T; Jiravský, O; Kociánová, E; Krátká, Z; Lambert, L; Nykl, I; Petrák, O; Rappová, G; Rosa, J; Štrauch, B; Táborský, M; Toušek, P; Václavík, J; Waldauf, P; Widimský, J; Widimský, P; Zelinka, T, 2017)
" Prostasin was measured in plasma and urine from type 2 diabetic patients with resistant hypertension (n = 112) randomized to spironolactone/placebo in a clinical trial."	5.24	Albuminuria is associated with an increased prostasin in urine while aldosterone has no direct effect on urine and kidney tissue abundance of prostasin. ( Bistrup, C; Hansen, MR; Hansen, PB; Hinrichs, GR; Jacobsen, IA; Jensen, BL; Kurt, B; Oxlund, C; Schwarzensteiner, I; Stæhr, M; Svenningsen, P; Thuesen, AD; Toft, A, 2017)
"Enablement of more persistent spironolactone use with newer potassium-binding agents, the clinical development of novel nonsteroidal MRAs with a more favourable benefit-risk profile and the recently proven blood pressure lowering action of chlorthalidone are three therapeutic opportunities for more effective management of hypertension in high-risk patients with advanced CKD."	5.22	Management of hypertension in advanced kidney disease. ( Agarwal, R; Georgianos, PI, 2022)
"This randomized, multicenter study compared the relative efficacy of renal denervation (RDN) versus pharmacotherapy alone in patients with true resistant hypertension and assessed the effect of spironolactone addition."	5.22	Role of Adding Spironolactone and Renal Denervation in True Resistant Hypertension: One-Year Outcomes of Randomized PRAGUE-15 Study. ( Bednář, F; Branny, M; Čurila, K; Holaj, R; Indra, T; Jiravský, O; Kociánová, E; Krátká, Z; Lambert, L; Nykl, I; Petrák, O; Rappová, G; Rosa, J; Štrauch, B; Táborský, M; Toušek, P; Václavík, J; Waldauf, P; Widimský, J; Widimský, P; Zelinka, T, 2016)
"Low-dose spironolactone has been proven to be effective for resistant hypertension in the general population, but this has yet to be confirmed in type 2 diabetic (T2DM) patients."	5.22	Effect of low-dose spironolactone on resistant hypertension in type 2 diabetes mellitus: a randomized controlled trial in a sub-Saharan African population. ( Djoumessi, RN; Essouma, M; Kaze, FF; Kengne, AP; Mbanya, JC; Menanga, AP; Noubiap, JJ; Sobngwi, E, 2016)
"The Eplerenone on parathyroid hormone levels in patients with primary hyperparathyroidism (EPATH) trial is a single-center, randomized, double-blind, parallel-group, placebo-controlled trial."	5.22	Effect of eplerenone on parathyroid hormone levels in patients with primary hyperparathyroidism: results from the EPATH randomized, placebo-controlled trial. ( Aberer, F; Alesutan, I; Belyavskiy, E; Brussee, H; Dimai, HP; Fahrleitner-Pammer, A; Gaksch, M; Grübler, M; Haas, J; Hartaigh, BÓ; Horina, JH; Lang, F; März, W; Meinitzer, A; Ofner-Ziegenfuss, L; Pieske, B; Pieske-Kraigher, E; Pilz, S; Ritz, E; Rus-Machan, J; Schwetz, V; Stiegler, C; Tomaschitz, A; Verheyen, N; Verheyen, S; Voelkl, J, 2016)
"For most adults with resistant hypertension, spironolactone is superior to doxazosin and bisoprolol as an adjunct to triple therapy."	5.22	PURLs: Resistant hypertension? Time to consider this fourth-line drug. ( Kaysin, A; Mounsey, A, 2016)
"Both renal denervation (RDN) and spironolactone have been proposed for the treatment of resistant hypertension."	5.22	Spironolactone versus sympathetic renal denervation to treat true resistant hypertension: results from the DENERVHTA study - a randomized controlled trial. ( Armario, P; Clarà, A; De la Sierra, A; Oliveras, A; Pascual, J; Sans-Atxer, L; Vázquez, S, 2016)
"This prospective, randomized, open-label multicenter trial evaluated the efficacy of catheter-based renal denervation (Symplicity, Medtronic) versus intensified pharmacological treatment including spironolactone (if tolerated) in patients with true-resistant hypertension."	5.20	Randomized comparison of renal denervation versus intensified pharmacotherapy including spironolactone in true-resistant hypertension: six-month results from the Prague-15 study. ( Bednář, F; Branny, M; Čurila, K; Holaj, R; Jiravský, O; Kociánová, E; Nykl, I; Petrák, O; Rosa, J; Šomlóová, Z; Štrauch, B; Táborský, M; Toušek, P; Václavík, J; Waldauf, P; Widimský, J; Widimský, P; Zelinka, T, 2015)
"Spironolactone was the most effective add-on drug for the treatment of resistant hypertension."	5.20	Spironolactone versus placebo, bisoprolol, and doxazosin to determine the optimal treatment for drug-resistant hypertension (PATHWAY-2): a randomised, double-blind, crossover trial. ( Brown, MJ; Caulfield, MJ; Cruickshank, JK; Ford, I; MacDonald, TM; Mackenzie, I; McInnes, G; Morant, S; Padmanabhan, S; Salsbury, J; Sever, P; Webb, DJ; Williams, B, 2015)
"The PATHWAY-2 study, funded by the British Heart Foundation, randomised 335 patients with resistant hypertension (already treated according to guidelines) to sequentially receive 12 weeks of spironolactone (25-50 mg), bisoprolol (5-10 mg), doxazosin (4-8 mg modified release) and placebo."	5.20	[PATHWAY-2 Study: spironolactone vs placebo, bisoprolol and doxazosin to determine optimal treatment of resistant hypertension. Spironolactone high effective in lowering blood pressure in drug resistant hypertension]. ( Widimský, J, 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)
"The purpose of this study was to evaluate the effects of spironolactone on dialysis patients with refractory hypertension and possible adverse effects."	5.19	Effects of spironolactone on dialysis patients with refractory hypertension: a randomized controlled study. ( Chen, J; Ni, X; Wu, F; Xia, M; Ying, G; Zhang, J; Zhang, P, 2014)
"Addition of low-dose eplerenone to renin-angiotensin system inhibitors might have renoprotective effects through reduction of albuminuria in hypertensive patients with non-diabetic chronic kidney disease, without serious safety concerns."	5.19	Anti-albuminuric effect of the aldosterone blocker eplerenone in non-diabetic hypertensive patients with albuminuria: a double-blind, randomised, placebo-controlled trial. ( Ando, K; Arakawa, Y; Fujita, T; Kaname, S; Ohtsu, H; Uchida, S, 2014)
"This study was designed to assess the effect of the addition of low-dose spironolactone on blood pressure (BP) in patients with resistant arterial hypertension."	5.19	Effect of spironolactone in resistant arterial hypertension: a randomized, double-blind, placebo-controlled trial (ASPIRANT-EXT). ( Jarkovský, J; Kociánová, E; Sedlák, R; Táborský, M; Václavík, J, 2014)
"There are currently limited data on whether the effect of spironolactone in patients with resistant arterial hypertension depends on age and sex."	5.19	Effect of spironolactone in patients with resistant arterial hypertension in relation to age and sex: insights from the aspirant trial. ( Jarkovsky, J; Kocianova, E; Sedlak, R; Taborsky, M; Vaclavik, J, 2014)
"In HRE patients without previous hypertension, short-term spironolactone reduced exercise BP, 24-hour ambulatory BP, LVMI, and E/e(m) but did not significantly alter exercise capacity or myocardial strain."	5.17	Impact of spironolactone on vascular, myocardial, and functional parameters in untreated patients with a hypertensive response to exercise. ( Hare, JL; Jenkins, C; Leano, R; Marwick, TH; Sharman, JE; Wright, L, 2013)
"The primary objective of this study was to evaluate the antihypertensive effect of low dose spironolactone added to triple therapy for resistant hypertension in patients with type 2 diabetes measured by ambulatory monitoring."	5.17	Low dose spironolactone reduces blood pressure in patients with resistant hypertension and type 2 diabetes mellitus: a double blind randomized clinical trial. ( Gram, J; Henriksen, JE; Jacobsen, IA; Oxlund, CS; Schousboe, K; Tarnow, L, 2013)
" We wanted to test the hypotheses that amiloride and spironolactone induced potassium retention reduces ambulatory blood pressure (ABP) and central blood pressure (CBP) during baseline conditions and after furosemide and that the tubular transport via the epithelial sodium channels (ENaCs) and aquaporin-2 (AQP2) water channels was increased by furosemide in arterial hypertension."	5.17	Effect of amiloride and spironolactone on renal tubular function and central blood pressure in patients with arterial hypertension during baseline conditions and after furosemide: a double-blinded, randomized, placebo-controlled crossover trial. ( Jensen, JM; Larsen, T; Lauridsen, TG; Matthesen, SK; Pedersen, EB; Vase, H, 2013)
"There are currently limited data about whether the effect of spironolactone in patients with resistant arterial hypertension depends on baseline blood pressure and the presence of a secondary cause of hypertension."	5.17	The effect of spironolactone in patients with resistant arterial hypertension in relation to baseline blood pressure and secondary causes of hypertension. ( Jarkovsky, J; Kocianova, E; Sedlak, R; Taborsky, M; Vaclavik, J, 2013)
"Recent studies from our laboratory indicate that chlorthalidone triggers persistent activation of the sympathetic nervous system and promotes insulin resistance in hypertensive patients, independent of serum potassium."	5.16	Spironolactone prevents chlorthalidone-induced sympathetic activation and insulin resistance in hypertensive patients. ( Adams-Huet, B; Arbique, D; Auchus, RJ; Price, A; Raheja, P; Vongpatanasin, W; Wang, Z, 2012)
" The aim was to compare the effects on albuminuria of the therapy with either: (i) telmisartan 80 mg and aliskiren 300 mg, (ii) telmisartan 80 mg and eplerenone 50 mg, (iii) telmisartan 160 mg as monotherapy."	5.16	The enhanced renin-angiotensin-aldosteron system pharmacological blockade--which is the best?. ( Bednarski, R; Donderski, R; Heleniak, Z; Lizakowski, S; Manitius, J; Przybylska, M; Renke, M; Rutkowski, B; Rutkowski, P; Sulikowska, B; Tylicki, L, 2012)
"If spironolactone proves effective, it might become the standard of treatment in patients with resistant arterial hypertension."	5.15	Addition of spironolactone in patients with resistant arterial hypertension (ASPIRANT)--study protocol. ( Husar, R; Kocianova, E; Navratil, K; Plachy, M; Plasek, J; Sedlak, R; Taborsky, M; Vaclavik, J, 2011)
"The objectives were to determine effects of spironolactone and chlorthalidone on SNA and the role of SNA on diuretic-induced insulin resistance in human hypertension."	5.14	Differential effects of chlorthalidone versus spironolactone on muscle sympathetic nerve activity in hypertensive patients. ( Adams-Huet, B; Arbique, D; Auchus, RJ; Menon, DV; Vongpatanasin, W; Wang, Z, 2009)
" Of the 6,632 patients with acute myocardial infarctions and left ventricular systolic dysfunction in the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS), 4,407 had histories of hypertension."	5.14	A history of systemic hypertension and incident heart failure hospitalization in patients with acute myocardial infarction and left ventricular systolic dysfunction. ( Ahmed, A; Pitt, B, 2009)
" 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)
"Spironolactone did not change the overall ability to autoregulate GFR in 16 hypertensive type 1 diabetic patients with normoalbuminuria."	5.14	Autoregulation of glomerular filtration rate during spironolactone treatment in hypertensive patients with type 1 diabetes: a randomized crossover trial. ( Boomsma, F; Christensen, PK; Jorsal, A; Parving, HH; Rossing, P; Schjoedt, KJ, 2009)
"The role of spironolactone in resistant hypertension management is unclear."	5.14	Efficacy of spironolactone therapy in patients with true resistant hypertension. ( de Souza, F; Fiszman, R; Muxfeldt, E; Salles, G, 2010)
" We conducted a double-blind, placebo-controlled trial in 81 patients with diabetes, hypertension, and albuminuria (urine albumin-to-creatinine ratio > or =300 mg/g) who all received lisinopril (80 mg once daily)."	5.14	Addition of angiotensin receptor blockade or mineralocorticoid antagonism to maximal angiotensin-converting enzyme inhibition in diabetic nephropathy. ( Adams-Huet, B; Mehdi, UF; Raskin, P; Toto, RD; Vega, GL, 2009)
"The aim of the study was evaluation of spironolactone effect on concentration of endothelin-1 (ET-1 - vasoconstrictive substance produced by endothelial cells) and aldosterone (Ald) and plasma renin activity (PRA) in patients with primary arterial hypertension (AH): group A--smoking patients (11 individuals) in comparison with group B--non-smoking ones (12 individuals)."	5.14	[Does spironolactone use at arterial hypertension therapy protect endothelium also in smoking patients?]. ( Kara-Perz, H; Kosicka, T; Perz, S, 2009)
"To determine the efficacy and safety of eplerenone therapy in children with hypertension."	5.14	The efficacy and safety of the novel aldosterone antagonist eplerenone in children with hypertension: a randomized, double-blind, dose-response study. ( Davis, I; Flynn, JT; Li, JS; Ogawa, M; Portman, R; Pressler, ML; Shi, H, 2010)
"To determine the efficacy of spironolactone (SPIRO) and hydrochlorothiazide (HCTZ) as monotherapy in older patients with hypertension in blood pressure (BP) control and measures of vascular stiffness."	5.14	Spironolactone and hydrochlorothiazide decrease vascular stiffness and blood pressure in geriatric hypertension. ( Kithas, PA; Supiano, MA, 2010)
"In the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (n=6632), eplerenone-associated reduction in all-cause mortality was significantly greater in those with a history of hypertension (Hx-HTN)."	5.13	History of hypertension and eplerenone in patients with acute myocardial infarction complicated by heart failure. ( Ahmed, A; Aschermann, M; Cardoso, JS; Corbalán, R; Krum, H; Love, TE; Nicolau, J; Parkhomenko, A; Pitt, B; Shi, H; Solomon, H; Zannad, F, 2008)
"The aim of this prospective, randomised, open-label, blinded-end point study was to compare the efficacy and safety of eplerenone versus spironolactone in patients with bilateral idiopathic hyperaldosteronism (IHA)."	5.13	Spironolactone versus eplerenone for the treatment of idiopathic hyperaldosteronism. ( Anagnostis, P; Athyros, VG; Kakafika, AI; Karagiannis, A; Mikhailidis, DP; Pagourelias, ED; Papageorgiou, A; Tziomalos, K, 2008)
" Studies comparing the effect of spironolactone to placebo in patients with hypertension and DM were included."	5.12	A systematic review and meta-analysis of effects of spironolactone on blood pressure, glucose, lipids, renal function, fibrosis and inflammation in patients with hypertension and diabetes. ( Abudoyreyimu, R; Heizati, M; Li, N; Lin, M; Nurula, M; Wang, L; Wang, Z; Wu, Z; Yang, Z, 2021)
"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)
"Spironolactone is recommended as fourth-line therapy for essential hypertension despite few supporting data for this indication."	5.12	Effect of spironolactone on blood pressure in subjects with resistant hypertension. ( Chapman, N; Dahlöf, B; Dobson, J; Poulter, NR; Sever, PS; Wedel, H; Wilson, S, 2007)
" It is not known if subjects with a high ratio have aldosteronism or aldosterone-sensitive hypertension is debated but it is important to know whether spironolactone is superior to other diuretics such as bendroflumethiazide in this setting."	5.12	Does the aldosterone:renin ratio predict the efficacy of spironolactone over bendroflumethiazide in hypertension? A clinical trial protocol for RENALDO (RENin-ALDOsterone) study. ( Alhashmi, K; Connell, JM; Ford, I; MacDonald, TM; McInnes, GT; McMahon, AD; Parthasarathy, HK; Struthers, AD, 2007)
"This study compared the efficacy and tolerability of eplerenone and enalapril in 499 patients with stage 1 or 2 hypertension who were randomized to receive eplerenone or enalapril for 6 months in a 3-step titration-to-effect study."	5.11	Efficacy of eplerenone versus enalapril as monotherapy in systemic hypertension. ( Burgess, E; Kipnes, MS; Kolloch, RE; Krause, SL; Niegowska, J; Patrick, JL; Roniker, B; Ruilope, LM; Williams, GH, 2004)
"The effect of spironolactone, cilazapril and their combination on albuminuria was examined in a randomized prospective study in female patients with diabetes and hypertension."	5.11	The effect of spironolactone, cilazapril and their combination on albuminuria in patients with hypertension and diabetic nephropathy is independent of blood pressure reduction: a randomized controlled study. ( Amit, M; Berla, M; Kedar, Y; Levi, Z; Rachmani, R; Ravid, M; Slavachevsky, I, 2004)
"Thirty medically treated ambulatory hypertensive patients (19 women, age 62+/-6 years) with exertional dyspnea, ejection fraction >50%, and diastolic dysfunction (E/A <1, E deceleration time >250 m/sec) and without ischemia were randomized to spironolactone 25 mg/d or placebo for 6 months."	5.11	Effect of aldosterone antagonism on myocardial dysfunction in hypertensive patients with diastolic heart failure. ( Cowley, D; Haluska, B; Leano, R; Marwick, TH; Mottram, PM; Stowasser, M, 2004)
"Ten patients with type II diabetes and hypertension were enrolled in a randomized, double-blind crossover study comparing 4 months' treatment with spironolactone and placebo with a 4-week washout phase."	5.11	Spironolactone reduces brachial pulse wave velocity and PIIINP levels in hypertensive diabetic patients. ( Band, M; Davies, J; Gavin, A; Morris, A; Struthers, A, 2005)
"In the present uncontrolled pilot study, we evaluate the short-term (8 weeks) effects of spironolactone on proteinuria in 42 patients with chronic kidney disease (CKD) already treated with ACE inhibitors and/or ARBs."	5.11	Antagonists of aldosterone and proteinuria in patients with CKD: an uncontrolled pilot study. ( Bianchi, S; Bigazzi, R; Campese, VM, 2005)
"This 16-week, multicenter, double-blind, active-controlled, parallel-group, titration-to-effect trial compared the blood pressure and neurohumoral responses of the selective aldosterone blocker eplerenone (100-200 mg/d; n = 86) with those of the angiotensin receptor blocker losartan (50-100 mg/d; n = 82) in patients with low-renin hypertension (active renin < or = 25 pg/mL [< or = 42."	5.11	Effects of eplerenone versus losartan in patients with low-renin hypertension. ( Davidson, RC; Krause, SL; MacDonald, TM; Patrick, JL; Roniker, B; Ruilope, LM; Weinberger, MH; White, WB, 2005)
"Eplerenone, a selective aldosterone blocker (SAB) that is highly specific for the aldosterone receptor, has the potential to be efficacious in the treatment of hypertension."	5.10	Eplerenone, a selective aldosterone blocker, in mild-to-moderate hypertension. ( Krause, SL; Roniker, B; Weinberger, MH; Weiss, RJ, 2002)
"This study shows that spironolactone improves impaired fibrinolysis in systemic hypertension."	5.10	Effect of spironolactone on impaired fibrinolysis of hypertensive patients. ( Aslan, V; Dincer, M; Gulbas, Z; Yalcin, AI, 2002)
"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)
"Black (n = 348) and white (n = 203) patients with mild-to-moderate hypertension were randomized to double-blind treatment with eplerenone 50 mg, the angiotensin II receptor antagonist losartan 50 mg, or placebo once daily."	5.10	Efficacy and tolerability of eplerenone and losartan in hypertensive black and white patients. ( Flack, JM; Garthwaite, S; Kleiman, JH; Krause, SL; Oparil, S; Pratt, JH; Roniker, B; Saunders, E; Workman, D; Yang, Y, 2003)
"Eplerenone is a highly selective aldosterone blocker, which is under development for the treatment of hypertension and heart failure."	5.10	Effects of the selective aldosterone blocker eplerenone versus the calcium antagonist amlodipine in systolic hypertension. ( Duprez, D; Krause, S; Kuse-Hamilton, J; Roniker, B; St Hillaire, R; Weber, MA; White, WB, 2003)
"Eplerenone is a highly selective aldosterone blocking agent, which was recently approved for the treatment of hypertension and has also been shown to reduce mortality in post-myocardial infarction patients with heart failure."	5.10	Assessment of the novel selective aldosterone blocker eplerenone using ambulatory and clinical blood pressure in patients with systemic hypertension. ( Carr, AA; Jordan, R; Krause, S; Oigman, W; Roniker, B; White, WB, 2003)
" We sought to compare the magnitude of the distress induced by a widely used calcium channel blocking agent, amlodipine, and a new aldosterone antagonist, eplerenone, in patients treated for systolic hypertension."	5.10	Symptoms and the distress they cause: comparison of an aldosterone antagonist and a calcium channel blocking agent in patients with systolic hypertension. ( Akhras, KS; Anderson, R; Bittman, RM; Hollenberg, NK; Krause, SL; Williams, GH, 2003)
" This study compared LVH regression during treatment with the selective aldosterone blocker eplerenone, enalapril, and their combination in patients with hypertension."	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)
"Previous reports have demonstrated the antihypertensive efficacy of high doses of spironolactone in subjects with primary aldosteronism and, to a lesser degree, subjects with resistant hypertension."	5.10	Efficacy of low-dose spironolactone in subjects with resistant hypertension. ( Calhoun, DA; Nishizaka, MK; Zaman, MA, 2003)
"Eplerenone therapy was effective in the treatment of mild to moderate hypertension over a 14-month period, either as monotherapy or in combination with another antihypertensive agent."	5.10	Long-term safety and efficacy of the selective aldosterone blocker eplerenone in patients with essential hypertension. ( Burgess, ED; Kleiman, JH; Krause, S; Lacourcière, Y; Maurath, C; Oparil, S; Roniker, B; Ruilope-Urioste, LM, 2003)
" 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)
"The study was undertaken to determine the possible effect of an aldosterone antagonist, spironolactone (SP), on red blood cell sodium-hydrogen exchange (NHE) enhancement in primary aldosteronism (PA) and essential hypertension (EH)."	5.08	Spironolactone prevents Na+/H+ exchange enhancement in primary aldosteronism. ( Koldanov, R; Koren, W; Postnov, IY; Postnov, YV, 1997)
"To investigate the effects of the association spironolactone (25 mg)/altizide (15 mg) as monotherapy on left ventricular hypertrophy (LVH) in patients with mild to moderate hypertension."	5.08	Effects of spironolactone-altizide on left ventricular hypertrophy. ( Brohet, C; Cosyns, J; Degre, S; Detry, JM; Kormoss, N; Unger, P, 1998)
"The relation between vasodilation and the blood pressure-reducing action of spironolactone was studied in a randomized, placebo-controlled, double-blind, crossover study using 9 patients with essential hypertension."	5.06	Peripheral action of spironolactone: plethysmographic studies. ( Clement, DL, 1990)
"A large-scale, open, nonrandomized, multicenter, 90-day study of the safety and efficacy of a thiazide diuretic and aldosterone antagonist combination (Aldactazine, 25 mg spironolactone and 15 mg altizide, 1/day) as monotherapy was performed in 946 patients with mild to moderate hypertension (diastolic blood pressure [BP] between 90 and 120 mm Hg)."	5.06	Clinical update: spironolactone and altizide as monotherapy in systemic hypertension. ( Dueymes, JM, 1990)
"The safety and antihypertensive effectiveness of a fixed-dose combination form of spironolactone + altizide (S/A) were compared with those of enalapril, an angiotensin-converting enzyme inhibitor in a randomized, double-blind, parallel-group study of 186 patients with moderate essential hypertension."	5.06	Spironolactone and altizide versus converting enzyme inhibitor (enalapril). ( Capron, MH; Grünfeld, JP; Pelletier, B; Wehrlen, M, 1990)
"The addition of enalapril or acebutolol to a regimen of altizide + spironolactone in patients with moderate hypotension was investigated in a multicenter study of 53 patients."	5.06	Spironolactone and altizide used in combination with enalapril: twenty-four-hour ambulatory recording of blood pressure. ( Capron, MH; Pelletier, B; Poncelet, P; Wehrlen, M, 1990)
"In a double-blind, randomized, multicenter study of 194 patients with moderate hypertension, spironolactone and nifedipine were found to reduce blood pressure (BP) to about the same extent and in the same percentage of patients after 45 days of treatment (47 and 50%, respectively)."	5.06	Spironolactone versus nifedipine in essential hypertension. ( Capron, MH; Henry, M; Pelletier, B; Wehrlen, M, 1990)
"The aim of this study was to compare the efficacy and safety of enalapril and a combination of a thiazide diuretic (altizide) and a diuretic that reduce potassium excretion (spironolactone), in patients presenting moderate essential hypertension."	5.06	[Efficacy and tolerability of enalapril compared to altizide combined with spironolactone in patients with moderate arterial hypertension]. ( Baudouy, M; Camous, JP; Durand, P; Gibelin, P; Morand, P, 1986)
"The effect of adding spironolactone (Aldactone) on muscle electrolytes was studied in 48 patients with arterial hypertension and/or congestive heart failure who had received conventional diuretic treatment, including a potassium supplement, for more than 1 year."	5.06	Effects of spironolactone on serum and muscle electrolytes in patients on long-term diuretic therapy for congestive heart failure and/or arterial hypertension. ( Dyckner, T; Wester, PO; Widman, L, 1986)
"We conducted a meta-analysis to summarize all available evidence from randomized controlled trial studies regarding the clinical efficacy and safety of spironolactone in patients with resistant hypertension (RH) and provided a quantitative assessment."	5.05	Clinical efficacy and safety of spironolactone in patients with resistant hypertension: A systematic review and meta-analysis. ( Chen, C; Li, D; Lin, Q; Zhou, K; Zhu, XY, 2020)
"Nineteen patients with uncomplicated essential hypertension and low activity of plasma renin in response to a change from recumbency to an upright posture along with furosemide administration were given spironolactone, 400 mg/d, or chlorthalidone, 100mg/d, in a double-blind, random-sequence, crossover trial."	5.05	Comparison of chlorthalidone and spironolactone in low--renin essential hypertension. ( Kreeft, JH; Larochelle, P; Ogilvie, RI, 1983)
"57 years), with primary arterial hypertension, was submitted to two periods of treatment in a cross-over study with spironolactone and potassium canrenoate."	5.05	[Clinical study of the efficacy of oral potassium canrenoate and spironolactone in essential arterial hypertension]. ( Fanti, P; Mantellini, R; Sciarra, F; Tosti-Croce, C, 1983)
" They had simultaneously started therapy with, or increased the dosage of, chlorthalidone or hydrochlorothiazide for the treatment of hypertension."	5.05	Serum cholesterol during treatment of hypertension with diuretic drugs. ( Ames, RP; Peacock, PB, 1984)
"Once-a-day therapy with spironolactone has been compared with a twice-a-day regimen in an open crossover trial in patients with essential hypertension."	5.05	Comparison of a single-dose and twice-a-day spironolactone therapy in mild hypertension. ( Dynon, M; Louis, WJ; Ludbrook, A; Mendelsohn, FA, 1980)
"The effects of placebo and of a spironolactone-althiazide combination in the treatment of twenty-two Kenyan Africans with hypertension were assessed using a double-blind technique."	5.05	The use of a spironolactone and althiazide combination (aldactacine) in the treatment of benign essential hypertension. ( Mngola, EN, 1980)
"Since there is only scanty, indirect information about the mechanism of the hypotensive effect of spironolactone, 9 patients with essential hypertension were studied according to a randomised double-blind, cross-over protocol."	5.05	Effect of spironolactone on systemic blood pressure, limb blood flow and response to sympathetic stimulation in hypertensive patients. ( Clement, DL, 1982)
"The antihypertensive effects of hydrochlorothiazide and spironolactone when added to treatment with metoprolol were compared in a double-blind trial comprising 55 previously untreated patients with essential hypertension."	5.05	A double-blind comparison of spironolactone and hydrochlorothiazide in hypertensive patients treated with metoprolol. ( Hansson, L; Lavenius, B, 1982)
"The antihypertensive efficacy of combination therapy with the angiotensin-converting enzyme inhibitor captopril and a diuretic or a calcium antagonist was compared in 16 patients with essential hypertension with a blood pressure of over 160/95 mm Hg having triple drug therapy."	5.05	Antihypertensive treatment using calcium antagonists in combination with captopril rather than diuretics. ( Bolli, P; Brouwer, RM; Bühler, FR; Conen, D; Erné, P; Kiowski, W, 1985)
"This study was designed to compare the effectiveness of spironolactone, hydrochlorothiazide, and combined spironolactone-hydrochlorothiazide therapy in patients with low renin and those with normal renin essential hypertension."	5.04	Diuretic therapies in low renin and normal renin essential hypertension. ( Brooks, CS; Johnson, CA; Kotchen, JM; Kotchen, TA, 1977)
"The blood pressure lowering effects of spironolactone have been studied in 40 subjects with benign essential hypertension in an attempt to determine the optimum starting dose for the drug."	5.04	[Detection of the optimal dose of spironolactone for the treatment of benign essential hypertension]. ( Rhomberg, F, 1977)
"Hydrochlorothiazide (HCT) and spironolactone (SP), alone and in combination, were utilized in the treatment of 79 adult men with mild to moderate essential hypertension."	5.04	Antihypertensive effect and serum potassium homeostasis: comparison of hydrochlorothiazide and spironolactone alone and in combination. ( Nash, DT, 1977)
"In a single blind crossover trial, spironolactone (50 mg twice a day), and hydrochlorothiazide (50 mg twice a day) were equally effective hypotensive agents in 16 patients with untreated essential hypertension."	5.04	A comparison between spironolactone and hydrochlorothiazide with and without alpha-methyldopa in the treatment of hypertension. ( Friedman, A; Johnston, CI; Suthers, MB; Walter, NM, 1978)
"A double-blind study of hydrochlorothiazide and spironolactone, alone and in combination, was conducted in 49 patients with mild-to-moderate essential hypertension after a 4-wk placebo washout period."	5.04	Hydrochlorothiazide and spironolactone in hypertension. ( Schrijver, G; Weinberger, MH, 1979)
"The relative efficacies of potassium chloride, amiloride, triamterene and spironolactone in maintaining potassium balance were studied in 40 patients with essential hypertension receiving diuretic therapy."	5.04	Maintenance of potassium balance during diuretic therapy. ( Eisalo, A; Kohvakka, A; Manninen, V, 1979)
"In 61 out-patients with essential hypertension, grade I or II, propranolol was administered alone in increasing doses (3 x 40 mg/d or 3 x 80 mg/d) or, if there was insufficient response, with a double or triple combination consisting additionally of spironolactone (50 mg/d)-thiabutazide (5 mg/d) and dihydralazine (3 x 25 mg/d)."	5.04	[Treatment of essential hypertension with a combination of propranolol, spironolactone-thiabutazide and dihydralazine (author's transl)]. ( Ebel, H; Klaus, D; Lübke, H; Witzgall, H; Zehner, J, 1978)
"In a crossover study 32 patients with hypertension were randomly allocated to treatment with spironolactone 200 mg/day for two months, propranolol 320 mg/day for two months, and a combination of both drugs at half the dose."	5.04	Renin concentrations and effects of propranolol and spironolactone in patients with hypertension. ( Kågedal, B; Karlberg, BE; Tegler, L; Tolagen, K, 1976)
"The effect of a six-week course of spironolactone 300 mg/day was examined in 25 unselected patients with essential hypertension."	5.04	Spironolactone in essential hypertension: evidence against its effect through mineralocorticoid antagonism. ( Edmonds, CJ; Hoffbrand, BI; Smith, T, 1976)
"35 patients with benign essential hypertension were treated for 6 weeks with high doses of the mineralocorticoid-antagonist spironolactone (400 mg/day), or with the "loop-diuretic" mefruside (mean maximal dose 110 mg/day)."	5.04	[Correlations between blood pressure, blood volume and plasma renin during therapy with diuretics in essential hypertension. Comparison between the mineralocorticoid antagonist spironolactone and the "loop" diuretic mefruside]. ( Beretta-Piccoli, C; de Châtel, R; Hirsch, D; Reubi, FC; Weidmann, P, 1977)
"The effect on BP of 100 and 200 mg spironolactone/day has been compared with that of methyl-dopa, 750 mg/day, and with combined treatment with both drugs in 32 patients with essential hypertension."	5.04	The effect of spironolactone (Aldactone) and methyldopa in low and normal renin hypertension. ( Giezendanner, L; Solheim, SB; Sundsfjord, JA, 1975)
"To review comparative efficacy and tolerability data between the two main mineralocorticoid receptor antagonists (MRAs), spironolactone and eplerenone, in patients with resistant hypertension (HTN)."	5.01	Eplerenone Versus Spironolactone in Resistant Hypertension: an Efficacy and/or Cost or Just a Men's Issue? ( Manolis, AA; Manolis, AS; Manolis, TA; Melita, H, 2019)
"This study was designed to assess the effect of additional spironolactone on blood pressure in patients with resistant hypertension."	4.95	Addition of spironolactone in patients with resistant hypertension: A meta-analysis of randomized controlled trials. ( Ju, Y; Liu, L; Xu, B, 2017)
"The efficacy of add-on use of spironolactone in patients with resistant hypertension has been investigated in several small studies."	4.95	A meta-analysis of add-on use of spironolactone in patients with resistant hypertension. ( Dong, P; Liu, H; Zhao, D; Zhao, J, 2017)
"To assess the effects of eplerenone monotherapy versus placebo for primary hypertension in adults."	4.95	Eplerenone for hypertension. ( Kinkade, A; Masson, SC; Stabler, SN; Tam, TS; Tejani, AM; Tsang, MP; Tung, A; Wu, MH, 2017)
"The role of eplerenone in arterial hypertension has been investigated only in small studies."	4.90	Efficacy and safety of eplerenone in the management of mild to moderate arterial hypertension: systematic review and meta-analysis. ( Gaudio, C; Greco, C; Patti, G; Pelliccia, F; Rosano, G, 2014)
"(2) In RALES, low-dose spironolactone in addition to standard of care, produced a 30% improvement in survival in progressive heart failure, commonly assumed to reflect deleterious effects of aldosterone, with spironolactone competing with aldosterone for cardiac mineralocorticoid receptors."	4.86	Aldosterone, hypertension and heart failure: insights from clinical trials. ( Funder, JW, 2010)
"Spironolactone is an aldosterone antagonist, considered fourth line therapy for hypertension in patients already treated with multiple medications."	4.86	Spironolactone for hypertension. ( Batterink, J; Fowkes, CT; Stabler, SN; Tejani, AM, 2010)
"To review the pharmacology, pharmacokinetics, pharmacodynamics, efficacy data, and adverse effects of spironolactone in the treatment of resistant hypertension."	4.86	Spironolactone management of resistant hypertension. ( Marrs, JC, 2010)
" A newer agent, eplerenone, has been recently licensed for the treatment of heart failure and in the US also for hypertension."	4.84	Evaluation of the aldosterone-blocking agent eplerenone in hypertension and heart failure. ( George, J; Struthers, AD, 2007)
" 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)
"Pharmacia Corp (formerly GD Searle & Co) is developing eplerenone, an aldosterone receptor antagonist, as a potential treatment for congestive heart failure and systemic hypertension."	4.82	Eplerenone. Pharmacia. ( Krum, H; Liew, D; Martin, J, 2003)
" 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)
"The goal of this article was to review the pharmacologic properties, clinical efficacy, and tolerability of eplerenone in the treatment of hypertension, LV dysfunction, and proteinuria."	4.82	The cardiovascular effects of eplerenone, a selective aldosterone-receptor antagonist. ( Davis, KL; Nappi, JM, 2003)
" The selective aldosterone blocker, eplerenone (Inspra), is under development for human therapeutic use for treatment of hypertension and heart failure post-myocardial infarction (MI)."	4.82	Aldosterone target organ protection by eplerenone. ( McMahon, EG; Rocha, R; Rudolph, AE, 2004)
" Recently published data with a new aldosterone blocker, eplerenone, have confirmed the benefits of aldosterone blockade in patients post-myocardial infarction, as well as in the regression of left ventricular hypertrophy in hypertensive patients and of microalbuminuria in Type 2 diabetic patients."	4.82	Role of the selective aldosterone receptor blockers in arterial hypertension. ( Ruilope, LM; Sierra, C, 2004)
" 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)
"Eplerenone is a selective aldosterone blocker (SAB) approved for the treatment of essential hypertension."	4.82	Eplerenone: a review of its use in essential hypertension. ( Croom, KF; Perry, CM, 2005)
" The 30% improvement in mortality (and 35% in morbidity) seen in the RALES trial with the addition of low-dose spironolactone to best practice therapy in moderate to severe heart failure, similarly points to an unrecognized role for aldosterone in the pathophysiology of heart failure."	4.81	Mineralocorticoid receptors and pathophysiological roles for aldosterone in the cardiovascular system. ( Funder, JW; Young, MJ, 2002)
"In a 16-week study, eplerenone was more effective than placebo or losartan in lowering systolic blood pressure (BP) and diastolic BP in black patients with mild to moderate hypertension."	4.81	Clinical implications of aldosterone blockade. ( Weber, MA, 2002)
" The therapeutic efficacy of spironolactone (Pharmacia Corp) in severe chronic heart failure is established."	4.81	The role of aldosterone receptor blockade in the management of cardiovascular disease. ( Krum, H; Liew, D, 2002)
"Until recently, spironolactone was considered only as an antagonist at the aldosterone receptors of the epithelial cells of the kidney and was used clinically in the treatment of hyperaldosteronism and, occasionally, as a K(+)-sparing diuretic."	4.81	The spironolactone renaissance. ( Brown, L; Doggrell, SA, 2001)
"Eplerenone, an aldosterone receptor antagonist from Searle is being developed as a potential treatment for renal disease, congestive heart failure and hypertension."	4.81	Eplerenone (GD Searle & Co). ( Krum, H; Martin, J, 2001)
" In our study, we studied if continuous treatment with a mineralocorticoid receptor antagonist, spironolactone (30 mg/kg/day) for 20 days can: 1) attenuate hypertension development and restore inverted 24-h BP rhythm in hypertensive transgenic (mRen-2)27 rats (TGR) measured by telemetry; 2) improve function of the kidneys and heart; 3) be protective against high salt load (1% in water) by mitigating oxidative injury and improving kidney function."	4.31	Mineralocorticoid receptor blockade protects the kidneys but does not affect inverted blood pressure rhythm in hypertensive transgenic (mRen-2)27 rats. ( Kopkan, L; Majzunova, M; Molcan, L; Sutovska, H; Sykora, M; Zeman, M, 2023)
"Nebivolol is an eﬀective treatment option for resistant hypertension and the antihypertensive eﬀect of nebivolol is similar to low-dose spironolactone."	4.31	Antihypertensive Efficacy Of Nebivolol And Low Dose Spironolactone In Patients With Resistant Hypertension. ( Avcı, Y; Bıyık, İ; Çizgici, AY; Demir, AR; Özal, E; Püşüroğlu, H, 2023)
"The aim of this study was to determine whether arterial stiffness assessed with the biochemical parameter active matrix metalloproteinase (MMP)-9 and the clinical parameters pulse pressure (PP) and pulse wave velocity predicts the response to spironolactone in resistant hypertension (RH)."	4.12	Prediction of the early response to spironolactone in resistant hypertension by the combination of matrix metalloproteinase-9 activity and arterial stiffness parameters. ( Aceves-Ripoll, J; Alvarez-Llamas, G; Baldan-Martin, M; Barderas, MG; de la Cuesta, F; González-Lafuente, L; Navarro-García, JA; Rodríguez-Sánchez, E; Ruilope, LM; Ruiz-Hurtado, G; Segura, J, 2022)
"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)
"Identify blood pressure (BP) response to spironolactone in patients with apparent therapy-resistant hypertension (aTRH) using electronic medical records (EMRs) in order to estimate response in a real-world clinical setting."	3.96	Retrospective cohort study to characterise the blood pressure response to spironolactone in patients with apparent therapy-resistant hypertension using electronic medical record data. ( Brown, N; Luther, JM; Nian, H; Perkins, B; Shuey, M; Yu, C, 2020)
"In the PATHWAY-2 study of resistant hypertension, spironolactone reduced blood pressure substantially more than conventional antihypertensive drugs."	3.88	Endocrine and haemodynamic changes in resistant hypertension, and blood pressure responses to spironolactone or amiloride: the PATHWAY-2 mechanisms substudies. ( Brown, MJ; Caulfield, MJ; Cruickshank, JK; Ford, I; MacDonald, TM; Mackenzie, IS; McInnes, GT; Morant, SV; Padmanabhan, S; Salsbury, J; Sever, P; Webb, DJ; Williams, B, 2018)
"Seventeen Phase III studies conducted in patients with mild-to-moderate hypertension in the Eplerenone Hypertension Clinical Program were reviewed; eleven met the selection criteria."	3.88	Antihypertensive effect of the mineralocorticoid receptor antagonist eplerenone: a pooled analysis of patient-level data from comparative trials using regulatory-approved doses. ( Abreu, P; Beckerman, B; Burgess, E; Fernet, M; Lins, K; Vincent, J, 2018)
"Refractory hypertension is a recently described phenotype of antihypertensive treatment failure defined as uncontrolled blood pressure (BP) despite the use of ≥5 different antihypertensive agents, including chlorthalidone and spironolactone."	3.85	White-Coat Effect Is Uncommon in Patients With Refractory Hypertension. ( Calhoun, DA; Judd, EK; Oparil, S; Siddiqui, M, 2017)
"Spironolactone, which is a potent mineralocorticoid receptor antagonist, represents the first line medical treatment of primary aldosteronism (PA)."	3.83	SFE/SFHTA/AFCE consensus on primary aldosteronism, part 7: Medical treatment of primary aldosteronism. ( Herpin, D; Lefebvre, H; Pechère-Bertschi, A, 2016)
"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)
"Cross-sectional data of the single-center "Eplerenone in Primary Hyperparathyroidism" trial were used."	3.83	Parathyroid hormone, aldosterone-to-renin ratio and fibroblast growth factor-23 as determinants of nocturnal blood pressure in primary hyperparathyroidism: the eplerenone in primary hyperparathyroidism trial. ( Belyavskiy, E; Brandenburg, VM; Brussee, H; Catena, C; Fahrleitner-Pammer, A; Gaksch, M; Grübler, MR; März, W; Meinitzer, A; Perl, S; Pieske, B; Pilz, S; Scharnagl, H; Sechi, LA; Tomaschitz, A; Van Ballegooijen, AJ; Verheyen, N; Wetzel, J, 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)
"Mineralocorticoid receptor (MR) antagonists, such as spironolactone (SPI) and eplerenone (EPL), are useful for treating hypertension and heart failure."	3.81	DSR-71167, a novel mineralocorticoid receptor antagonist with carbonic anhydrase inhibitory activity, separates urinary sodium excretion and serum potassium elevation in rats. ( Fujita, K; Fukuda, N; Hasegawa, F; Hori, S; Iwata, M; Katayama, S; Kato, H; Kawane, K; Matsuda, K; Mori, M; Nakayama, R; Nariai, T; Suzuki, K, 2015)
" In this study, the effect of add-on eplerenone on the degree of arterial stiffness was examined in patients with uncontrolled hypertension."	3.81	Effects of Add-on Therapy Consisting of a Selective Mineralocorticoid Receptor Blocker on Arterial Stiffness in Patients with Uncontrolled Hypertension. ( Hasegawa, J; Hongo, K; Mori, C; Murashima, E; Sato, N; Shibata, T; Tsutsumi, J; Yoshimura, M, 2015)
"MBG-induced vascular fibrosis is a likely target for spironolactone."	3.81	Marinobufagenin-induced vascular fibrosis is a likely target for mineralocorticoid antagonists. ( Bagrov, AY; Bagrov, KA; Emelianov, IV; Fedorova, OV; Frolova, EV; Grigorova, YN; Juhasz, O; Konradi, AO; Lakatta, EG; Marshall, CA; Wei, W, 2015)
"Early spironolactone treatment decreases heart failure development frequency by improving myocardial systolic and diastolic function and attenuating hypertrophy and fibrosis in spontaneously hypertensive rats."	3.81	Early Spironolactone Treatment Attenuates Heart Failure Development by Improving Myocardial Function and Reducing Fibrosis in Spontaneously Hypertensive Rats. ( Blotta, DA; Bonomo, C; Campos, DH; Cezar, MD; Cicogna, AC; Damatto, RL; Gomes, MJ; Lima, AR; Martinez, PF; Okoshi, K; Okoshi, MP; Oliveira, SA; Pagan, LU; Rosa, CM, 2015)
"Angiotensin II (Ang II) and aldosterone contribute to hypertension, oxidative stress and cardiovascular damage, but the contributions of aldosterone during Ang II-dependent hypertension are not well defined because of the difficulty to assess each independently."	3.81	Angiotensin and mineralocorticoid receptor antagonism attenuates cardiac oxidative stress in angiotensin II-infused rats. ( Conte, D; Minas, JN; Nishiyama, A; Ortiz, RM; Thorwald, MA; Vázquez-Medina, JP, 2015)
"Eplerenone is a highly selective aldosterone blocker, which has the potential to lower blood pressure (BP) in patients with hypertension."	3.80	The velocity of home blood pressure reduction in response to low-dose eplerenone combined with other antihypertensive drugs determined by exponential decay function analysis. ( Asayama, K; Elnagar, N; Hosaka, M; Imai, Y; Ishikura, K; Mano, N; Obara, T; Ohkubo, T; Satoh, M, 2014)
"The objective of this study was to identify factors associated with the blood pressure (BP) response to spironolactone--aldosterone receptor antagonist as an add-on therapy in patients with resistant hypertension (HTN)."	3.80	Serum potassium levels predict blood pressure response to aldosterone antagonists in resistant hypertension. ( Grossman, E; Leibowitz, A; Sella, T; Sharabi, Y; Shlomai, G, 2014)
"Spironolactone attenuates interstitial fibrosis and cardiomyocyte hypertrophy in hypertensive heart disease."	3.80	Cardiac magnetic resonance assessment of interstitial myocardial fibrosis and cardiomyocyte hypertrophy in hypertensive mice treated with spironolactone. ( Coelho-Filho, OR; Jerosch-Herold, M; Kwong, R; Mitchell, R; Moreno, H; Neilan, TG; Shah, RV, 2014)
"Spironolactone is often used to treat hypertension caused by hyperaldosteronism, and as a result, can form concentrically laminated electron dense spironolactone body inclusions within the adrenal gland."	3.80	Adrenal gland inclusions in patients treated with aldosterone antagonists (Spironolactone/Eplerenone): incidence, morphology, and ultrastructural findings. ( Calomeni, EP; Nadasdy, T; Patel, KA; Zynger, DL, 2014)
"In C57BL/6-mice, hypertension was induced by infusion of 600 ng/kg • min angiotensin II."	3.80	Oxidative DNA damage in kidneys and heart of hypertensive mice is prevented by blocking angiotensin II and aldosterone receptors. ( Amann, K; Brand, S; Mandel, P; Schupp, N; Zimnol, A, 2014)
"A total of 6,575 patients with hypertension treated between January 1, 2000, and November 30, 2012, were evaluated for the safety of an aldosterone-blocking agent (spironolactone) added to preexisting blood pressure-lowering regimens."	3.80	Predictors of hyperkalemia risk after hypertension control with aldosterone blockade according to the presence or absence of chronic kidney disease. ( Gwoo, S; Jung, YS; Kim, YN; Rim, H; Shin, HS, 2014)
"A chronic increase in circulating angiotensin II (Ang II) activates an aldosterone-mineralocorticoid receptor-ouabain neuromodulatory pathway in the brain that increases neuronal activation in hypothalamic nuclei, such as the paraventricular nucleus (PVN) and causes progressive hypertension."	3.79	Central mineralocorticoid receptors and the role of angiotensin II and glutamate in the paraventricular nucleus of rats with angiotensin II-induced hypertension. ( Gabor, A; Leenen, FH, 2013)
"Aim of the study is to evaluate the impact of spironolactone (SPL) on indexes of metabolic syndrome (MS) and further investigate the mechanisms underlying its protective effects."	3.79	Spironolactone prevents dietary-induced metabolic syndrome by inhibiting PI3-K/Akt and p38MAPK signaling pathways. ( Liang, LY; Lin, YE; Liu, MJ; Long, HD; Zeng, ZH, 2013)
"Circulating angiotensin II (Ang II) activates a central aldosterone-mineralocorticoid receptor neuromodulatory pathway, which mediates most of the Ang II-induced hypertension."	3.79	Role of brain corticosterone and aldosterone in central angiotensin II-induced hypertension. ( Ahmad, M; Huang, BS; Leenen, FH; White, RA, 2013)
" METHODS 70 spontaneous hypertensive rats of 8-week age, 200-gram weight were separated into 7 groups, as hypertension, ramipril, telmisartan, eplerenone, ramipril + telmisartan, telmisartan + eplerenone, and ramipril+eplerenone treatment group."	3.79	[Effect of RAAS antagonist on the expression of gap junction cx43 in myocardium of spontaneously hypertensive rat]. ( Li, L; Liu, LM; Tan, LL; Zhao, HL, 2013)
"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)
"Add-on therapy with eplerenone effectively lowers BP in patients with difficult-to-treat primary hypertension."	3.79	Determinants of blood pressure reduction by eplerenone in uncontrolled hypertension. ( Arnoldus, JH; Danser, AH; de Bruijne, EL; Deinum, J; Frenkel, WJ; Jansen, PM; Kerstens, MN; van den Born, BJ; van den Meiracker, AH; Wijbenga, JA; Woittiez, AJ; Zietse, R, 2013)
" In the present study, we investigated the contribution of aldosterone to the renal p21 expression and senescence during the development of angiotensin II (AngII)-induced hypertension."	3.78	Aldosterone does not contribute to renal p21 expression during the development of angiotensin II-induced hypertension in mice. ( Deguchi, K; Hitomi, H; Kitada, K; Kobori, H; Lei, B; Masaki, T; Minamino, T; Mori, H; Nakano, D; Nishiyama, A, 2012)
"The aim of this paper is to report a case of unilateral PA with spontaneous remission and reduction of cardiac hypertrophy after long-term spironolactone (SP) therapy."	3.78	Unilateral primary aldosteronism with spontaneous remission after long-term spironolactone therapy. ( Demura, M; Karashima, S; Kometani, M; Takata, H; Takeda, Y; Yamagishi, M; Yoneda, T, 2012)
"To investigate whether exposure to spironolactone treatment affects the risk of incident breast cancer in women over 55 years of age."	3.78	Spironolactone and risk of incident breast cancer in women older than 55 years: retrospective, matched cohort study. ( Macdonald, TM; Mackenzie, IS; Morant, S; Thompson, A; Wei, L, 2012)
"Mineralocorticoid receptor (MR) antagonists, such as spironolactone (SPI) and eplerenone (EPL), are useful for the treatment of hypertension and heart failure."	3.77	SM-368229, a novel selective and potent non-steroidal mineralocorticoid receptor antagonist with strong urinary Na+ excretion activity. ( Fujita, K; Hori, S; Katayama, S; Matsui, K; Mori, M; Nariai, T, 2011)
"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)
" To test the hypothesis that aldosterone can cause hypertension in a manner that does not involve renal sodium retention, we administered eplerenone, a specific aldosterone antagonist, to oligo-anuric chronic hemodialysis patients who had HTN."	3.77	Effect of eplerenone on blood pressure and the renin-angiotensin-aldosterone system in oligo-anuric chronic hemodialysis patients - a pilot study. ( Lifschitz, M; Neykin, D; Shavit, L; Slotki, I, 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)
" Oral dosing of 3S,3aR-27d (PF-3882845) in the Dahl salt sensitive preclinical model of salt-induced hypertension and nephropathy showed blood pressure attenuation significantly greater than that with eplerenone, reduction in urinary albumin, and renal protection."	3.76	Discovery of (3S,3aR)-2-(3-chloro-4-cyanophenyl)-3-cyclopentyl-3,3a,4,5-tetrahydro-2H-benzo[g]indazole-7-carboxylic acid (PF-3882845), an orally efficacious mineralocorticoid receptor (MR) antagonist for hypertension and nephropathy. ( Arhancet, GB; Blinn, JR; Chen, X; Collins, JT; Dietz, JD; Garland, DJ; Heron, MI; Hockerman, SL; Homer, BL; Hu, X; Huang, HC; Long, SA; Mahoney, MW; McGee, KF; Meyers, MJ; Payne, MA; Reitz, DB; Rico, JR; Wendling, JM; Yang, S, 2010)
" It has been reported that eplerenone has a potential antihypertensive effect, with a profile slightly different from that of spironolactone, and has fewer adverse reactions, suggesting that it may become a first-line treatment for hypertension."	3.76	Clinical effects of eplerenone, a selective aldosterone blocker, in Japanese patients with essential hypertension. ( Fukuda, S; Sato, A, 2010)
" The addition of spironolactone to her previous medications controlled and normalized hypertension, hypokalemia, and hormonal abnormalities within 4 months."	3.76	Resistant hypertension in an aged woman presenting with clinical features simulating ectopic ACTH syndrome--response to spironolactone--. ( Harada, E; Mizuno, Y; Morikawa, Y; Nakagawa, H; Saito, Y; Semba, F; Yasue, H; Yoshimura, M, 2010)
"The aim of this study was to evaluate the use of spironolactone and doxazosin as treatment for patients with resistant hypertension."	3.75	Spironolactone and doxazosin treatment in patients with resistant hypertension. ( Baldó, E; Costa, JA; González, C; Pascual, JM; Pérez-Lahiguera, F; Rodilla, E, 2009)
"A fixed, low-dose of spironolactone, added to chronic ACE inhibitor therapy, reduced blood pressure and urinary albumin excretion in obese subjects with hypertension and preexistent target organ damage."	3.75	Low-dose spironolactone, added to long-term ACE inhibitor therapy, reduces blood pressure and urinary albumin excretion in obese patients with hypertensive target organ damage. ( Bald, E; Bomback, AS; Chwatko, G; Muskala, P; Nowicki, M, 2009)
" After 4 weeks of DOCA-salt hypertension, rats were either killed (n = 6), or treated with a non-hypotensive dose of spironolactone (n = 7) or triple therapy (hydrochlorothiazide, reserpine and hydralazine, n = 8) to normalize blood pressure or with vehicle (n = 19) for two further weeks."	3.74	Blood pressure versus direct mineralocorticoid effects on kidney inflammation and fibrosis in DOCA-salt hypertension. ( Cordasic, N; Hartner, A; Hilgers, KF; Klanke, B; Schmieder, RE; Veelken, R, 2008)
"Renal collecting duct (CD)-specific knockout of endothelin-1 (ET-1) causes hypertension and impaired Na excretion."	3.74	Role of the renin-angiotensin-aldosterone system in collecting duct-derived endothelin-1 regulation of blood pressure. ( Ge, Y; Huang, Y; Kohan, DE, 2008)
"3%) patients had primary hyperaldosteronism, and response to spironolactone treatment further confirmed this diagnosis."	3.74	Prevalence of primary hyperaldosteronism in resistant hypertension: a retrospective observational study. ( Douma, S; Doumas, M; Kartali, N; Papadopoulos, N; Papaefthimiou, P; Petidis, K; Triantafyllou, A; Vogiatzis, K; Zamboulis, C, 2008)
"Several studies have shown beneficial effects of eplerenone in hypertension and left ventricular dysfunction, but its action on cardiac and vascular changes secondary to blood pressure elevation are not clear yet."	3.74	Eplerenone offsets cardiac and aortic adverse remodeling in spontaneously hypertensive rats. ( Burla, AK; Mandarim-de-Lacerda, CA; Neves, MF; Oigman, W, 2007)
" To elucidate the potential role of local renin-angiotensin system in aldosterone-induced cardiovascular injury, we investigated the effects of selective mineralocorticoid receptor (MR) antagonist eplerenone (EPL), angiotensin (Ang) II type 1 receptor antagonist candesartan (ARB), and superoxide dismutase mimetic tempol (TEM) on the development of hypertension, vascular injury, oxidative stress, and inflammatory-related gene expression in aldosterone-treated hypertensive rats."	3.74	Angiotensin II receptor type 1-mediated vascular oxidative stress and proinflammatory gene expression in aldosterone-induced hypertension: the possible role of local renin-angiotensin system. ( Hirata, Y; Hirono, Y; Kobayashi, N; Sakurada, M; Shichiri, M; Sugiyama, T; Suzuki, N; Takai, S; Yoshimoto, T, 2007)
" Spironolactone, a mineralocorticoid receptor antagonist, decreases ischemic cerebral infarct size in male spontaneously hypertensive stroke-prone rats (SHRSP)."	3.74	Spironolactone improves structure and increases tone in the cerebral vasculature of male spontaneously hypertensive stroke-prone rats. ( Dorrance, AM; Pollock, DM; Rigsby, CS, 2007)
"We have conducted an open observational study of the use of spironolactone 25-50 mg in the management of patients with resistant hypertension."	3.74	Low-dose spironolactone in the management of resistant hypertension: a surveillance study. ( Beevers, DG; Lane, DA; Shah, S, 2007)
" With the discontinuation of the licorice-containing medicines and administration of spironolactone together with intravenous and oral potassium supplement, her serum potassium level was normalized and her clinical symptoms and hypertension improved within 2 weeks."	3.74	Severe hypokalemia, rhabdomyolysis, muscle paralysis, and respiratory impairment in a hypertensive patient taking herbal medicines containing licorice. ( Harada, E; Itoh, T; Mizuno, Y; Yasue, H, 2007)
" To elucidate its significance for myocardial fibrosis in the hypertensive heart, we used a mouse model with infusion of angiotensin II and examined results by histology, immunohistochemistry, in situ hybridization, and quantitative real-time reverse transcriptase polymerase chain reaction (RT-PCR)."	3.74	Eplerenone attenuates myocardial fibrosis in the angiotensin II-induced hypertensive mouse: involvement of tenascin-C induced by aldosterone-mediated inflammation. ( Hiroe, M; Imanaka-Yoshida, K; Inada, H; Nishioka, T; Onishi, K; Suzuki, M; Takakura, N; Yoshida, T, 2007)
"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)
"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)
"The combination of spironolactone with an ACE inhibitor for patients with heart failure may cause severe hyperkalemia."	3.73	[Successful resuscitation of a patient with hyperkalemic cardiac arrest by emergency hemodiafiltration]. ( Gütlich, D; Hochscherf, M; Hopf, HB, 2005)
"We describe a hypertensive nephrosclerosis patient presenting with severe hyperkalemia due to a combination therapy of the angiotensin receptor blocker (ARB) candesartan and spironolactone despite mildly decreased renal function."	3.73	Life-threatening hyperkalemia during a combined therapy with the angiotensin receptor blocker candesartan and spironolactone. ( Fujii, H; Inenaga, T; Kawano, Y; Nakahama, H; Nakamura, S; Yoshihara, F, 2005)
"We correlated the BP response to spironolactone 50 mg/day to baseline ARR in 69 hypertensive patients (mean [+/-SD] age 57 +/- 2 years, 65% male), consisting of 39 subjects with long-standing hypertension (4."	3.73	Does aldosterone-to-renin ratio predict the antihypertensive effect of the aldosterone antagonist spironolactone? ( Feely, J; Hall, M; Mahgoub, M; Mahmud, A, 2005)
"To compare efficacy of use of the blocker of aldosteron receptors spironolactone and diuretic indapamide in low-renin arterial hypertension (AH), their action on blood pressure, serum concentrations of sodium, potassium, creatinine, plasmic renin activity (PRA), plasmic aldosteron concentration (PAC)."	3.73	[Use of spironolactone and indapamide in the treatment of low-renin arterial hypertension]. ( Bagdonas, G; Kazanavichus, G; Naudzhunas, A; Yankauskene, L, 2006)
" Since chronic inhibition of nitric oxide (NO) synthase with N(omega)-nitro-L-arginine methyl ester (L-NAME) induces systemic hypertension associated with cardiovascular inflammation and remodeling, we examined the potential role of aldosterone in this process using eplerenone, a selective aldosterone receptor antagonist."	3.73	The antagonism of aldosterone receptor prevents the development of hypertensive heart failure induced by chronic inhibition of nitric oxide synthesis in rats. ( Asano, Y; Fujita, M; Hirata, A; Hori, M; Kitakaze, M; Minamino, T; Okada, K; Sanada, S; Shintani, Y; Takashima, S; Tomoike, H; Tsukamoto, O; Yamasaki, S; Yulin, L, 2006)
"We report the case of normoaldosterone spironolactone sensitive hypertension."	3.73	[Normoaldosterone spironolactone sensitive hypertension--a case report]. ( Herman, ZS; Krysiak, R; Okopień, B, 2005)
"We retrospectively analyzed the effectiveness of spironolactone, an aldosterone antagonist, used as add-on therapy, compared with a standard add-on treatment, in patients referred to a hypertension clinic with UH despite the use of two or more antihypertensive drugs."	3.73	Efficacy of add-on aldosterone receptor blocker in uncontrolled hypertension. ( Adler, E; Grossman, E; Markovitz, A; Nussinovitch, N; Shamis, A; Sharabi, Y, 2006)
"We report the case of normoaldosterone spironolactone sensitive hypertension."	3.73	[Normoaldosterone spironolactone sensitive hypertension]. ( Herman, ZS; Krysiak, R; Okopień, B, 2006)
"The effects of low-dose oral spironolactone (SPIRO) in a rat model of hypertensive heart failure (spontaneously hypertensive heart failure rat) were compared with its effects when combined with captopril (CAP)."	3.72	Combined effects of low-dose oral spironolactone and captopril therapy in a rat model of spontaneous hypertension and heart failure. ( Bauer, JA; Ghosh, S; Holycross, BJ; Kambara, A; Kwiatkowski, P; McCune, SA; Schanbacher, B; Wung, P, 2003)
"When performed with careful regard to confounding factors, measurement of the aldosterone : renin ratio in all hypertensive individuals, followed by fludrocortisone suppression testing to confirm or exclude primary aldosteronism and adrenal venous sampling to determine the subtype, can result in the detection of significant numbers of patients with specifically treatable or potentially curable hypertension."	3.72	High rate of detection of primary aldosteronism, including surgically treatable forms, after 'non-selective' screening of hypertensive patients. ( Archibald, C; Cowley, DC; Gordon, RD; Gunasekera, TG; Smithers, BM; Stowasser, M; Ward, G, 2003)
"The purpose of this study was to investigate the role of the renin-angiotensin-aldosterone system in hypertension development and cardiovascular structural changes in a salt-sensitive hypertensive model induced by capsaicin (CAP)."	3.72	Control of vascular changes by renin-angiotensin-aldosterone system in salt-sensitive hypertension. ( Gao, YJ; He, CC; Lee, RM; Li, N; Luo, BH; Su, CJ; Yi, JJ; Zeng, ZH, 2004)
" The lack of therapeutic response to spironolactone, with a good response to amiloride and recurrence of hypertension and metabolic alkalosis after amiloride cessation that was subsequently treated with amiloride, established the diagnosis of Liddle syndrome."	3.71	Liddle syndrome in a newborn infant. ( Assadi, FK; Kimura, RE; Patel, S; Subramanian, U, 2002)
"Aldosterone-induced hypertension is associated with renal damage that may be mediated by endothelin-1 (ET-1)."	3.71	Contribution of endothelin-1 to renal activator protein-1 activation and macrophage infiltration in aldosterone-induced hypertension. ( Chen, X; He, G; Schiffrin, EL; Tostes, RC; Touyz, RM, 2002)
" The present study investigated the effects of the aldosterone receptor antagonists spironolactone and eplerenone on endothelial function in liquorice-induced hypertension."	3.71	Aldosterone receptor antagonism normalizes vascular function in liquorice-induced hypertension. ( Lüscher, TF; Quaschning, T; Ruschitzka, F; Shaw, S, 2001)
" Inhibition of 11beta-HSD2 by liquorice-derived glycyrrhizic acid (GA) therefore results in sodium retention and hypertension."	3.71	Influence of aldosterone vs. endothelin receptor antagonism on renovascular function in liquorice-induced hypertension. ( Christ, M; Lunt, CM; Lüscher, TF; Niggli, B; Quaschning, T; Ruschitzka, F; Shaw, S; Wehling, M, 2001)
"The role of spironolactone as pemphigoid-inducing agent has recently been suggested."	3.71	[Bullous pemphigoid induced by spironolactone]. ( Cordel, N; Courville, P; Gilbert, D; Joly, P; Lauret, P; Modeste, AB, 2002)
"Spironolactone is a safe, effective therapy for patients with refractory hypertension."	3.71	The role of spironolactone in the treatment of patients with refractory hypertension. ( Carré, E; Lincoff, AM; Mertes, M; Ouzan, J; Pérault, C, 2002)
"Spironolactone and standard-dose RU 486 did not modify adrenocorticotrophin-induced hypertension despite demonstrable antimineralocorticoid and antiglucocorticoid actions."	3.70	Adrenocorticotrophin-induced hypertension: effects of mineralocorticoid and glucocorticoid receptor antagonism. ( Fraser, T; Li, M; Wen, C; Whitworth, JA, 1999)
" The antistroke effects of captopril treatment occurred without an antihypertensive effect, weren't altered by enhancing hypertension during treatment (with dexamethasone), and couldn't be duplicated by antihypertensive treatment with hydralazine."	3.70	Effect of poststroke captopril treatment on mortality associated with hemorrhagic stroke in stroke-prone rats. ( King, SR; Smeda, J; Vasdev, S, 1999)
" Five of these patients with aldosterone producing adenoma were operated on and four patients with idiopathic hyperaldosteronism were treated with spironolactone."	3.70	Insulin action in primary hyperaldosteronism before and after surgical or pharmacological treatment. ( Haas, T; Hilgertová, J; Prázný, M; Sindelka, G; Skrha, J; Widimský, J, 2000)
"A case of primary aldosteronism is presented in which the CT scan was initially misleading, adrenocortical scintigraphy was rendered inaccurate by pharmacological interference of spironolactone, and selective adrenal venous sampling of aldosterone was technically difficult."	3.69	Interference by spironolactone on adrenocortical scintigraphy and other pitfalls in the location of adrenal abnormalities in primary aldosteronism. ( Freitas, JE; Grekin, R; Gross, MD; Shapiro, B, 1994)
"A retrospective analysis was performed regarding age and sex of the patients, duration of hypertension, family history of hypertension, preoperative blood pressure, plasma aldosterone concentration (PAC), plasma renin activity (PRA) and efficacy of spironolactone on blood pressure between both groups."	3.69	Prognostic factors of primary aldosteronism. ( Chang, CH; Chang, CL; Chang, YY; Ho, HC; Lin, HS; Ou, YC; Wu, HC; Yang, CR, 1996)
"This study was designed to define the dose-response relationships for cortisol-induced hypertension in humans and to test the hypothesis that cortisol-induced hypertension is a consequence of classical mineralocorticoid actions using the mineralocorticoid antagonist spironolactone."	3.69	Dose-response relationships and mineralocorticoid activity in cortisol-induced hypertension in humans. ( Kelly, JJ; Whitworth, JA; Williamson, PM, 1996)
" Finally, potassium-sparing diuretics, especially spironolactone, play an important role in controlling high blood pressure in patients with primary aldosteronism."	3.69	[The clinical spectrum of potassium-sparing diuretics]. ( Greminger, P; Suter, PM, 1997)
"A case of primary aldosteronism treated with spironolactone therapy has been followed up for 24 years."	3.68	Twenty-four year spironolactone therapy in an aged patient with aldosterone-producing adenoma. ( Hashimoto, T; Ito, Y; Koshida, H; Miyamori, I; Morimoto, S; Morise, T; Takeda, R; Yamazaki, T, 1992)
" We have found that the infusion of both glycyrrhizic acid, an active principle of licorice, and carbenoxolone, a synthetic analogue, into a lateral ventricle of the brain [intracerebroventricular (icv)] of a rat, at a dose less than that which has an effect when infused subcutaneously, produces hypertension."	3.68	Central hypertensinogenic effects of glycyrrhizic acid and carbenoxolone. ( Gomez-Sanchez, CE; Gomez-Sanchez, EP, 1992)
"The effects of the mineralocorticoid antagonist mespirenone on the development and maintenance of aldosterone-induced hypertension in Sprague-Dawley rats has been studied."	3.68	Effect of a new mineralocorticoid antagonist mespirenone on aldosterone-induced hypertension. ( Agarwal, M; Kalimi, M; Opoku, J; Qureshi, D, 1991)
"Hypertension was induced in male rats by administration of a glucocorticoid agonist, RU 26988."	3.67	[Effect of an antiglucocorticoid steroid on the arterial hypertension induced by glucocorticoids in the rat]. ( Eloy, L; Ganeval, D; Grünfeld, JP; Moura, AM; Ramos-Frendo, B; Worcel, M, 1984)
"Intrarenal sodium handling was studied in 8 patients with essential hypertension before spironolactone treatment (200 mg/day), on the 4th day of treatment, and after 3 months of treatment."	3.67	Intrarenal sodium handling during chronic spironolactone treatment. ( Boer, P; Dorhout Mees, EJ; Koomans, HA; Roos, JC, 1984)
" Hypertension, hypokalaemia, hyperaldosteronism and renin suppression were corrected by unilateral adrenalectomy in 3/5 patients and by spironolactone treatment in 2/5."	3.67	Primary aldosteronism is comprised of primary adrenal hyperplasia and adenoma. ( Arteaga, EE; Biglieri, EG; Kater, CE, 1984)
"This study investigated the anti-mineralocorticoid potency and haemodynamic effects of a series of mineralocorticoid antagonists of the spirolactone type (RU 28318, spironolactone, K-prorenoate, K-canrenoate and canrenone), for their ability to prevent the development of ACTH-induced hypertension in conscious sheep."	3.67	Studies on spirolactone steroid antagonists in ACTH-induced hypertension in sheep. ( Coghlan, JP; Reid, AF; Scoggins, BA; Spence, CD; Whitworth, JA, 1989)
"The syndrome of apparent mineralocorticoid excess combines the features of unexplained but spironolactone-correctable mineralocorticoid excess in association with a decreased rate of oxidation of cortisol to cortisone."	3.67	A new form of the syndrome of apparent mineralocorticoid excess. ( Chan, CK; Edassery, J; Mantero, F; Rao, KN; Ulick, S, 1989)
"The use of spironolactone in the treatment of hypertension has been limited by the occurrence of sexual side effects, mainly menstrual disturbances in women and gynaecomastia in men."	3.67	Antialdosterones: incidence and prevention of sexual side effects. ( Corvol, P; de Gasparo, M; Jeunemaître, X; Ménard, J; Preiswerk, G; Whitebread, SE, 1989)
" Lasilactone, a new combination diuretic (furosemide 20 mg and spironolactone 50 mg) was evaluated in 30 patients with mild-to-moderate essential hypertension."	3.67	Efficacy and safety of lasilactone, a new combination diuretic, in essential hypertension. ( Birbari, AE; Daouk, MM; Mukaddam-Daher, S, 1987)
"The prognosis of hypertension was evaluated pre-operatively in 40 patients with primary aldosteronism owing to adenoma by examining the severity of hypertension, family history of hypertension, age of the patients, duration of hypertension, plasma renin activity, plasma aldosterone concentration, and efficacy of spironolactone (100 mg per day for 10 days) on blood pressure."	3.67	Pre-operative evaluation of the prognosis of hypertension in primary aldosteronism owing to adenoma. ( Murai, M; Saito, I; Saruta, T; Suzuki, H; Takita, T; Tazaki, H, 1987)
"The long-term efficacy and tolerance of spironolactone in essential hypertension was evaluated among 20,812 patients referred to the Broussais and St."	3.67	Efficacy and tolerance of spironolactone in essential hypertension. ( Charru, A; Chatellier, G; Corvol, P; DeVries, C; Jeunemaitre, X; Kreft-Jais, C; Menard, J; Plouin, PF, 1987)
" In six patients with Bartter's syndrome, four with pseudo-Bartter's syndrome, and twenty with essential hypertension (EH) chronically treated with chlorthalidone, serum potassium (serum K+) and extracellular fluid volume (ECFV) were decreased, while plasma volume (PV) and blood volume (BV) were normal (see Table 1 for means, standard deviations, and levels of significance)."	3.67	Blood to interstitial fluid volume ratio in chronic hypokalaemic states. ( Boer, P; Dorhout Mees, EJ; Geyskes, GG; Hené, RJ; Koomans, HA; Roos, JC; Van Shaik, BA, 1985)
" Blood pressure was normal during treatment with spironolactone and during pregnancy, when the action of aldosterone and other similar steroids was presumably blocked by an increased production of progesterone; this suggests that the hypertension is dependent upon sodium-retaining steroids such as aldosterone."	3.66	Overproduction of sodium-retaining steroids by the zona glomerulosa is adrenocorticotropin-dependent and mediates hypertension in dexamethasone-suppressible aldosteronism. ( Bartter, FC; Gill, JR, 1981)
"Spironolactone, an aldosterone antagonist, was given in a daily dose of 100 mg to 15 patients with primary hypertension for one year."	3.66	The effect of spironolactone on lipid, glucose and uric acid levels in blood during long-term administration to hypertensives. ( Falch, DK; Schreiner, A, 1983)
"To evaluate the role of the renin-angiotensin system and sodium depletion in the hypotensive response to 1-sarcosine-8-alanine-angiotensin II (saralasin), 15 male patients with essential hypertension were studied on a diet containing 120 mEq of sodium and 100 mEq of potassium per day."	3.66	Angiotensin II, plasma renin and sodium depletion as determinants of blood pressure response to saralasin in essential hypertension. ( Barrett, JD; Eggena, P; Golub, MS; Sambhi, MP; Thananopavarn, C, 1980)
"Spironolactone alone in full dosage failed to correct hypertension in a patient with Conn's syndrome and renal impairment, although the previously increased total exchangeable sodium fell to normal and the previously suppressed plasma angiotensin II did not rise above the normal range."	3.66	Combined captopril and spironolactone treatment in Conn's syndrome with renal impairment and refractory hypertension. ( Atkinson, AB; Brown, JJ; Davies, DL; Lever, AF; Robertson, JI, 1981)
"A 38-year-old woman with hypercalcemia, severe hypertension, and high renin levels was treated with the angiotensin-converting enzyme inhibitor captopril."	3.66	Hypertension in a patient with hypercalcemia: captopril and verapamil. ( Brunner, HR; Burckhardt, P; Gavras, H; Waeber, B, 1982)
"Intrarenal handling of uric acid was studied in 12 patients with essential hypertension under spironolactone treatment (200 mg/day)."	3.66	Changes in intrarenal uric acid handling during chronic spironolactone treatment in patients with essential hypertension. ( Boer, P; Dorhout Mees, EJ; Peuker, KH; Roos, JC, 1982)
"In view of recent evidence that spironolactone may inhibit synthesis of corticosteroids by a direct effect on the adrenal cortex, adrenocortical function was studied in eight patients with essential hypertension who had been treated with spironolactone from 3 months to 14 years."	3.66	Long term spironolactone and the adrenal cortex in essential hypertension. ( Gorchein, A; Horth, CE; James, VH; Lewis, PS; May, CN, 1980)
"Marked improvement in the severe hypertension (250/150 mmHg) and hirsutism of a patient suffering from polycystic ovary syndrome was quickly achieved by the use of spironolactone 200 mg per day."	3.66	Successful treatment of polycystic ovary syndrome with spironolactone or bromocriptine. ( Blum, I; Chovers, I; Kaufman, H; Marilus, R; Rusecki, Y, 1981)
" Plasma samples from non-digitalized patients of the following categories were assayed: uncomplicated essential hypertension treated with spironolactone, uremia, and acute myocardial infarction (AMI)."	3.66	Precision of digoxin radioimmunoassays and matrix effects: four kits compared. ( Bergdähl, B; Molin, L, 1981)
"In patients with hypertension resistant to three or four drugs including a thiazide diuretic substitution of frusemide for the thiazide, or the addition of spironolactone, produced significant reductions in blood pressure and body weight."	3.66	Diuretic treatment of resistant hypertension. ( Freestone, S; Ramsay, LE; Silas, JH, 1980)
") before and during treatment with spironolactone (Sp, 75--100 mg/day) for at least 8 months was studied in 11 patients with essential hypertension."	3.66	Reduced response of plasma aldosterone to acute ACTH stimulation during long-term treatment with spironolactone in essential hypertension. ( Kim, KS; Miyamori, I; Miyamoto, M; Morimoto, S; Takeda, R; Uchida, K, 1979)
"Thirty-two USAF aircrewmen with mild or moderate, uncomplicated essential hypertension were treated with Aldactazide (spironolactone and hydrochlorothiazide)."	3.66	Treatment of hypertension in aviators: a clinical trial with Aldactazide. ( Hull, DH; McAfoose, DA; Triebwasser, JH; Wolthuis, RA, 1978)
"To determine the effect of aldosterone antagonist on renal prostaglandin E synthesis, the rate of urinary excretion of immunoreactive prostaglandin E was measured radioimmunologically before and during the oral administration of an aldosterone antagonist, spironolactone, in 5 patients with essential hypertension, 3 with primary aldosteronism and 2 with postoperative primary aldosteronism."	3.66	Effect of spironolactone on urinary excretion of immunoreactive prostaglandin E in essential hypertension and primary aldosteronism. ( Abe, K; Chiba, S; Irokawa, N; Otsuka, Y; Sakurai, Y; Sato, M; Seino, M; Yasujima, M; Yoshinaga, K, 1978)
"The antihypertensive effect of spironolactone was studied in 20 patients with essential hypertension and normal stimulated peripheral renin activity (PRA)."	3.66	Antihypertensive responses to spironolactone in normal renin hypertension. ( Ogilvie, RI; Piafsky, KM; Ruedy, J, 1978)
"In order to evaluate the relationship between aldosterone status and the blood pressure-lowering effect of spironolactone, 38 patients with essential hypertension were treated with spironolactone (400 mg/day) during one week in hospital on a rigidly sodium-restricted diet."	3.66	Role of aldosterone in the antihypertensive effect of spironolactone in essential hypertension. ( Benraad, H; Benraad, T; Drayer, J; Hoefnagels, W; Kloppenborg, P, 1978)
"Minoxidil-induced sequential changes in plasma renin activity, urinary aldosterone and norepinephrine excretion were assessed in 11 patients with severe hypertension receiving propranolol or oxprenolol, chlorthalidone and spironolactone."	3.66	[Long-term minoxidil therapy: renin, aldosterone, noradrenaline and the need for beta blockers]. ( Brunner, HR; Ferguson, RK; Gavras, H; Jaeger, P; Jéquier, E; Turini, GA, 1978)
"The hypotensive effect of spironolactone and its relation to the changer in volaemia and renin activity induced by the drug were studied in 12 hospitalised patients with essential hypertension."	3.65	[Relations between hypotensive effect and modifications of volemia and plasma renin activity in patients with essential hypertension treated using spironolactone]. ( Corgnati, A; Palù, CD; Pessina, AC, 1977)
"Urinary kallikrein excretion was measured before and after administration of spironolactone in 12 patients with essential hypertension (including 7 patients with low renin and 5 patients with normal renin) and 6 patients with primary aldosteronism."	3.65	Effect of spironolactone on urinary kallikrein excretion in patients with essential hypertension and in primary aldosteronism. ( Abe, K; Chiba, S; Irokawa, N; Otsuka, Y; Sakurai, Y; Seino, M; Yasujima, M; Yoshinaga, K, 1977)
" Five patients with primary aldosteronism due to adenoma were followed during spironolactone treatment, for 35-55 days after the drug had been stopped, and finally, after surgery."	3.65	Volume-pressure relationships during development of mineralocorticoid hypertension in man. ( Derkx, FH; Man in 't Veld, AJ; Schalekamp, DH; Verhoeven, RP; Wenting, GH, 1977)
" Six of these patients were treated with spironolactone and developed gynecomastia."	3.65	Pathophysiology of spironolactone-induced gynecomastia. ( Kisch, ES; Newmark, SR; Rose, LI; Underwood, RH; Williams, GH, 1977)
"The effect of spironolactone on BP, cardiac output, plasma renin activity and urinary excretion of electrolytes has been studied in 12 hypertensive patients."	3.65	The effects of four months' treatment with spironolactone on systemic blood pressure, cardiac output and plasma renin activity in hypertensive patients. ( Bevegård, S; Castenfors, J; Danielson, M, 1977)
"The antihypertensive effect and the tolerance of the association of spironolactone and chlorthalidone were evaluated clinically and by numerous laboratory examinations in a group of 18 patients affected with non-complicated essential hypertension."	3.65	[Spironolactone combined with chlorthalidone in the treatment of essential arterial hypertension]. ( Favilli, R; Gragnoli, G; Nami, R; Puccetti, F; Tanganelli, I, 1975)
"The anti-hypertensive effect of spironolactone and thiabutazide was tested on 47 unselected patients with primary hypertension."	3.65	[Spironolactone and thiabutazide in the treatment of essential hypertension (author's transl)]. ( Braun, B; Klaus, D; Klump, F; Lemke, R; Zehner, J; Zöfel, P, 1975)
"The effect of prolonged preoperative treatment with spironolactone has been studied in a series of 67 patients with hypertension, aldosterone excess, and low plasma renin."	3.65	Comparison of surgery and prolonged spironolactone therapy in patients with hypertension, aldosterone excess, and low plasma renin. ( Brown, JJ; Davies, DL; Ferriss, JB; Fraser, R; Haywood, E; Lever, AF; Robertson, JI, 1972)
" of spironolactone (SL) in 48 patients with essential hypertension."	3.65	Treatment of hypertension with hydrochlorothiazide and spironolactone. ( Ogilvie, RI; Ruedy, J, 1969)
"Primary aldosteronism (PA) is the most common form of secondary hypertension."	3.01	Primary aldosteronism in pregnancy. ( Forestiero, V; Monticone, S; Mulatero, P; Sconfienza, E, 2023)
"For patients with treatment-resistant hypertension, guidelines recommend the addition of spironolactone to the baseline antihypertensive regimen."	3.01	Hypertension in chronic kidney disease-treatment standard 2023. ( Agarwal, R; Georgianos, PI, 2023)
"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)
"We considered that RSD could reduce the recurrence of AF in patients with CKD by modulating sympathetic hyperactivity."	2.87	Pulmonary vein isolation combined with spironolactone or renal sympathetic denervation in patients with chronic kidney disease, uncontrolled hypertension, paroxysmal atrial fibrillation, and a pacemaker. ( Chen, S; Hoye, NA; Kiuchi, MG; Pürerfellner, H, 2018)
"Spironolactone or HCTZ was randomly prescribed for 4 weeks."	2.87	Spironolactone is superior to hydrochlorothiazide for blood pressure control and arterial stiffness improvement: A prospective study. ( Dai, S; Liao, H; Liu, L; Liu, Y; Xiao, C, 2018)
"There is a lack of research on the effect of low dose of angiotensin receptor blockers combined with spironolactone, and the effect of high dose of angiotensin receptor blockers alone on the urinary albumin excretion rate (UAER) in elderly patients with early type 2 diabetic nephropathy (DN)."	2.87	Effects of Different Doses of Irbesartan Combined With Spironolactone on Urinary Albumin Excretion Rate in Elderly Patients With Early Type 2 Diabetic Nephropathy. ( Chen, X; Chen, Y; Li, Y; Liu, P; Wang, Y; Zhang, F, 2018)
"Spironolactone was more effective than SRD in reducing daytime systolic (P = 0."	2.84	Renal Denervation vs. Spironolactone in Resistant Hypertension: Effects on Circadian Patterns and Blood Pressure Variability. ( Armario, P; Barrera, Á; de la Sierra, A; Oliveras, A; Pareja, J; Pascual, J; Sans, L; Vázquez, S; Yun, S, 2017)
"Aldosterone excretion was determined by 24 h urine (24h-UAldo) collected at randomization and after 6 months of follow-up."	2.84	Effects of continuous positive airway pressure treatment on aldosterone excretion in patients with obstructive sleep apnoea and resistant hypertension: a randomized controlled trial. ( Cavalcanti, AH; Cortez, AF; de Souza, F; Margallo, V; Muxfeldt, ES; Salles, GF, 2017)
"INTRODUCTION Obstructive sleep apnea (OSA) is considered to be one of the major causes of resistant arterial hypertension (RAH)."	2.82	Effect of eplerenone on the severity of obstructive sleep apnea and arterial stiffness in patients with resistant arterial hypertension. ( Cofta, S; Krasińska, B; Krasiński, Z; Miazga, A; Pawlaczyk-Gabriel, K; Szczepaniak-Chicheł, L; Trafas, T; Tykarski, A, 2016)
"The treatment with eplerenone significantly increased serum potassium levels, whereas the treatment with indapamide significantly decreased them."	2.80	Effects of a selective aldosterone blocker and thiazide-type diuretic on blood pressure and organ damage in hypertensive patients. ( Hayashi, S; Ishizuka, A; Iwashima, Y; Kawano, Y; Kishida, M; Nakamura, S; Ohta, Y; Yoshihara, F, 2015)
"Resistant hypertension is inadequately controlled blood pressure (BP) despite treatment with at least three BP-lowering drugs."	2.80	Prevention And Treatment of Hypertension With Algorithm-based therapy (PATHWAY) number 2: protocol for a randomised crossover trial to determine optimal treatment for drug-resistant hypertension. ( Brown, MJ; Caulfield, M; Cruickshank, JK; Ford, I; MacDonald, TM; McInnes, G; Morant, S; Salsbury, J; Sever, P; Webb, DJ; Williams, B, 2015)
"Observational studies in primary hyperaldosteronism suggest a positive relationship between aldosterone and parathyroid hormone (PTH); however, interventions to better characterize the physiological relationship between the renin-angiotensin-aldosterone system (RAAS) and PTH are needed."	2.79	Human interventions to characterize novel relationships between the renin-angiotensin-aldosterone system and parathyroid hormone. ( Adler, GK; Brown, JM; Garg, R; Garza, AE; Luther, JM; Pojoga, LH; Ruan, DT; Vaidya, A; Williams, GH; Williams, JS, 2014)
"Eplerenone is a selective mineralocorticoid receptor antagonist; however, little is known about its effects on insulin action."	2.79	Effect of eplerenone on insulin action in essential hypertension: a randomised, controlled, crossover study. ( Atkinson, AB; Bell, PM; Ennis, C; Hunter, SJ; McMurray, EM; Wallace, IR, 2014)
"Amiloride (5 mg/d) was added to previous triple antihypertensive treatment (including a diuretic and an inhibitor of the renin-angiotensin-aldosterone system) and increased to 10 mg if BP control was not achieved at 4 weeks."	2.79	Amiloride lowers blood pressure and attenuates urine plasminogen activation in patients with treatment-resistant hypertension. ( Buhl, KB; Gram, J; Hansen, MR; Henriksen, JE; Jacobsen, IA; Jensen, BL; Oxlund, CS; Schousboe, K; Tarnow, L, 2014)
"Aldosterone breakthrough was observed in 22 of the subjects (55%)."	2.78	Effect of aldosterone breakthrough on albuminuria during treatment with a direct renin inhibitor and combined effect with a mineralocorticoid receptor antagonist. ( Fukuda, S; Sato, A, 2013)
"Hypertension is associated with endothelial dysfunction and activated Rho-associated kinases (ROCKs)."	2.77	Mineralocorticoid receptor blocker eplerenone improves endothelial function and inhibits Rho-associated kinase activity in patients with hypertension. ( Chayama, K; Fujii, Y; Fujimura, N; Hata, T; Hidaka, T; Higashi, Y; Idei, N; Iwamoto, Y; Kato, H; Kihara, Y; Liao, JK; Maruhashi, T; Mikami, S; Noma, K; Soga, J, 2012)
"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)
"Amiloride 40 mg was as effective as the other diuretics."	2.73	The spironolactone, amiloride, losartan, and thiazide (SALT) double-blind crossover trial in patients with low-renin hypertension and elevated aldosterone-renin ratio. ( Ashby, MJ; Brown, MJ; Hood, SJ; Taylor, KP, 2007)
"In atenolol-treated patients, the arterial wall became stiffer, whereas in the eplerenone-treated patients, it became less stiff and similar to that of a normotensive control group."	2.73	Selective mineralocorticoid receptor blocker eplerenone reduces resistance artery stiffness in hypertensive patients. ( Amiri, F; Savoia, C; Schiffrin, EL; Touyz, RM, 2008)
"The Taiwan Society of Aldosteronism (TSA) Task Force acknowledged the novel issues of PA and reached a group consensus on PA in Taiwan by collecting the best available evidence and conducting one group meeting, several conference calls, and multiple e-mail communications."	2.72	Taiwan mini-frontier of primary aldosteronism: Updating treatment and comorbidities detection. ( Chan, CK; Chang, YY; Chen, ZW; Huang, WC; Lin, YH; Tsai, YC; Wu, CY; Wu, KH; Wu, VC; Yen, IW, 2021)
"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)
"Aldosterone antagonism has BP-independent effects on arterial stiffness."	2.71	Aldosterone-to-renin ratio, arterial stiffness, and the response to aldosterone antagonism in essential hypertension. ( Feely, J; Mahmud, A, 2005)
"Primary hyperaldosteronism was confirmed if plasma renin activity was <1."	2.70	Hyperaldosteronism among black and white subjects with resistant hypertension. ( Calhoun, DA; Nishizaka, MK; Thakkar, RB; Weissmann, P; Zaman, MA, 2002)
"Spironolactone was a highly effective antihypertensive agent in hypertensive patients who had a raised aldosterone/renin ratio."	2.69	Raised aldosterone to renin ratio predicts antihypertensive efficacy of spironolactone: a prospective cohort follow-up study. ( Jung, RT; Lim, PO; MacDonald, TM, 1999)
" On long term evaluation in an open design (Phase II), wherein Phase I participants continued Terminalia Arjuna in fixed dosage (500 mg 8-hourly) in addition to flexible diuretic, vasodilator and digitalis dosage for 20-28 months (mean 24 months) on outpatient basis, patients showed continued improvement in symptoms, signs, effort tolerance and NYHA Class, with improvement in quality of life."	2.68	Salutary effect of Terminalia Arjuna in patients with severe refractory heart failure. ( Bharani, A; Bhargava, KD; Ganguly, A, 1995)
"Hypertension was associated with a significant increase in stroke volume and a non-significant increase in cardiac index."	2.68	[Conn's syndrome. Study of systemic cardiovascular hemodynamics after medical treatment with spironolactone and after surgical treatment]. ( Amah, G; Ben Maiz, H; Blacher, J; Girerd, X; Kheder, A; Safar, M, 1997)
" However, variability of plasma potassium within the dose interval was not increased markedly, and 12 hourly dosing is probably satisfactory for both potassium chloride and spironolactone at the doses studied."	2.67	Adequacy of twice daily dosing with potassium chloride and spironolactone in thiazide treated hypertensive patients. ( Brawn, LA; Ramsay, LE; Toner, JM; Yeo, WW, 1991)
"6%), and a low rate of adverse effects."	2.67	Aldactazine/captopril combination, safe and effective in mild to moderate systemic hypertension: report on a multicenter study of 967 patients. ( Capron, MH; Pelletier, B; Schohn, DC; Spiesser, R; Wehrlen, M, 1990)
"Aspirin has been shown to acutely block the natriuretic effect of spironolactone in the mineralocorticoid-treated normal rat, dog, and man."	2.64	Failure of aspirin to antagonize the antihypertensive effect of spironolactone in low-renin hypertension. ( Hollifield, JW, 1976)
"Oxprenolol was the best tolerated drug, with only 5% of patients withdrawing due to side-effects compared to 13% on spironolacone and 29% on methyldopa."	2.64	Renin unresponsiveness and the effects of oxprenolol, methyldopa and spironolactone in pateints with essential hypertension. ( Beilin, LJ; Ledingham, JG; Thomas, GW; Yeates, KM, 1976)
"Treatment with propranolol resulted in marked suppression of the plasma renin activity (1."	2.64	Intrapatient comparison of treatment with chlorthalidone, spironolactone and propranolol in normoreninemic essential hypertension. ( Benraad, TJ; Drayer, JI; Festen, J; Kloppenborg, PW; van't Laar, A, 1975)
" Triamterene seemed ineffective in the dosage used (50 mg twice daily)."	2.64	Potassium-sparing agents during diuretic therapy in hypertension. ( Brien, TG; Canning, BS; Donohoe, JF; Healy, JJ; McKenna, TJ; Muldowney, FP, 1971)
"Resistant hypertension is defined as a lack of ambulatory blood pressure response to optimized medical treatment after exclusion of secondary hypertension in patients who are fully adherent to antihypertensive therapy."	2.58	Diagnosis and management of resistant hypertension: state of the art. ( Huang, QF; Staessen, JA; Wei, FF; Zhang, ZY, 2018)
"Spironolactone has the best evidence as add-on pharmacologic therapy in patients with RH, but data are limited."	2.55	A Systematic Review of Add-on Pharmacologic Therapy in the Treatment of Resistant Hypertension. ( Barry, AR; Tataru, AP, 2017)
"Aldosterone also promotes collagen synthesis, which leads to increased arterial stiffness and elevation of blood pressure."	2.53	Resistant Hypertension and the Pivotal Role for Mineralocorticoid Receptor Antagonists: A Clinical Update 2016. ( Duprez, DA; Epstein, M, 2016)
" Randomised controlled trials investigating the effect of additional spironolactone on office blood pressure (BP), ambulatory BP or adverse events in RH patients were included for analysis."	2.53	Efficacy and Safety of Spironolactone in Patients with Resistant Hypertension: A Meta-analysis of Randomised Controlled Trials. ( Huang, J; Wang, C; Xiong, B, 2016)
"Hypertension is the leading cause of early mortality in the world, and reduction of blood pressure can help to reduce that burden."	2.53	Update in Hypertension Therapy. ( Mankin, LA, 2016)
"Primary aldosteronism with a prevalence of 8 % of hypertension and 20 % of pharmacologically resistant hypertension is the most common secondary cause of hypertension."	2.53	Diagnosing and Managing Primary Aldosteronism in Hypertensive Patients: a Case-Based Approach. ( Carey, RM, 2016)
"Resistant hypertension is a common clinical situation."	2.53	Should All Patients with Resistant Hypertension Receive Spironolactone? ( Holaj, R; Petrák, O; Rosa, J; Štrauch, B; Widimský, J; Zelinka, T, 2016)
" The range of adverse effects experienced with spironolactone has led to its modification and the consequent synthesis of eplerenone."	2.52	Efficacy and safety of mineralocorticoid receptors in mild to moderate arterial hypertension. ( Gaudio, C; Greco, C; Patti, G; Pelliccia, F; Rosano, G; Volterrani, M, 2015)
"Hypertension is one of the most common cardiovascular diseases during pregnancy."	2.52	[Hypertension in the course of primary aldosteronism during pregnancy]. ( Chudek, J; Maruniak-Chudek, I; Olszanecka-Glinianowicz, M; Sikora, J; Wyskida, K; Wyskida, M, 2015)
"Primary aldosteronism, caused by autonomous secretion of aldosterone by the adrenals, is estimated to account for at least 5% of hypertension cases."	2.52	Pharmacological treatment of aldosterone excess. ( Deinum, J; Lenders, JW; Riksen, NP, 2015)
" Clinical experience with Spironolactone is well established, as is its adverse effects profile."	2.50	Converging indications of aldosterone antagonists (spironolactone and eplerenone): a narrative review of safety profiles. ( Danjuma, MI; Makaronidis, J; Mukherjee, I; Osula, S, 2014)
"Apparent treatment-resistant hypertension (aTRH), defined as uncontrolled blood pressure using 3 or more antihypertensive medications or controlled using 4 or more antihypertensive medications, affects approximately 30% of uncontrolled and 12% of controlled blood pressure (BP) patients."	2.50	Role of aldosterone blockade in resistant hypertension. ( Egan, BM; Li, J, 2014)
" The dose-response relationship for natriuresis with spironolactone has not been explored completely as to its combination therapy responses."	2.50	Aldosterone and volume management in hypertensive heart disease. ( Sica, DA, 2014)
"The identification of primary aldosteronism as a common cause of resistant hypertension is a significant advance in our ability to care for patients with hypertension."	2.49	Endocrine and hypertensive disorders of potassium regulation: primary aldosteronism. ( Weiner, ID, 2013)
"Patients are diagnosed as having resistant hypertension when they have blood pressure readings that remain above goal despite the concomitant use of 3 optimally dosed antihypertensive agents from different classes, with 1 of the agents being a diuretic."	2.48	Evaluation and pharmacologic approach to patients with resistant hypertension. ( Adams, M; Bellone, JM; Rutecki, GW; Wright, BM, 2012)
"A close association exists between hyperaldosteronism, RHTN, and obstructive sleep apnea (OSA) based upon recent studies which indicate that OSA is worsened by aldosterone-mediated fluid retention."	2.48	Resistant hypertension and aldosterone: an update. ( Ahmed, MI; Calhoun, DA; Clark, D, 2012)
"Primary hyperaldosteronism (PHA) is characterized by an increased Aldosterone synthesis which is independent of the Renin-Angiotensin-Aldosterone-System (RAAS)."	2.48	[Primay hyperaldosteronism--diagnostic and treatment]. ( Beuschlein, F; Potthoff, SA; Vonend, O, 2012)
"Hypertension is a major risk factor for cardiovascular disease, but control of hypertension remains inadequate, often because of poor patient adherence to prescribed medical regimens that are viewed as poorly tolerated and expensive."	2.47	Older blood pressure medications-do they still have a place? ( Black, HR; Slim, HB; Thompson, PD, 2011)
"Primary hyperaldosteronism will be the most common etiology."	2.47	[Primary hyperaldosteronism]. ( Chambaz, IC; Pechère-Bertschi, A, 2011)
"Aldosterone was in the past considered only as a prohypertensinogenic agent."	2.46	Aldosterone in uremia - beyond blood pressure. ( Koleganova, N; Ritz, E, 2010)
"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)
"The primary hyperaldosteronism (PHA) is the most prevalent form (8-10%) of secondary causes of hypertension among hypertensive subjects."	2.45	[Conn's syndrome]. ( Born-Frontsberg, E; Quinkler, M, 2009)
"Eplerenone has been reported to have anti-hypertensive and protective effects on cardiovascular and renal injury in salt-sensitive hypertensive animal models, such as the Dahl salt-sensitive (DS) hypertensive rat and leptin receptor-deficient spontaneously hypertensive rat (SHR/cp)."	2.45	Effects of eplerenone, a selective mineralocorticoid receptor antagonist, on clinical and experimental salt-sensitive hypertension. ( Takeda, Y, 2009)
"Primary hyperaldosteronism is characterised by hypertension, hypokalemia, suppressed plasma renin activity, and increased aldosterone excretion."	2.45	Rhabdomyolysis due to primary hyperaldosteronism. ( Corrales, PP; López, AH; Martínez, JJ; Meneses, AL; Oliveira, CL; Rodríguez, SA; Romero, FB, 2009)
"Features of visceral obesity and obstructive sleep apnea that may stimulate aldosterone secretion are described here."	2.44	Obesity, sleep apnea, aldosterone, and hypertension. ( Goodfriend, TL, 2008)
"Aldosterone is an important mediator in the pathogenesis of heart failure, and increased plasma aldosterone levels are associated with a poor prognosis."	2.44	Drug insight: aldosterone-receptor antagonists in heart failure--the journey continues. ( Francis, GS; Kalidindi, SR; Tang, WH, 2007)
"Both agents effectively treat hypertension and heart failure but comparisons are complicated by the deficiency of head-to-head trials and differences between patient populations."	2.44	A comparison of the aldosterone-blocking agents eplerenone and spironolactone. ( Krum, H; Struthers, A; Williams, GH, 2008)
"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)
"Primary aldosteronism is a much more common cause of secondary hypertension than once suspected, accounting for approximately 10% of cases."	2.43	The pharmacological treatment of primary aldosteronism. ( Bouloux, PM; Janmohamed, S, 2006)
"Resistant hypertension is defined as blood pressure that remains above target levels despite treatment with three different antihypertensive agents."	2.43	Aldosterone antagonists: effective add-on therapy for the treatment of resistant hypertension. ( Calhoun, DA; Gaddam, KK; Pratt-Ubunama, MN, 2006)
"The prevalence of primary hyperaldosteronism is 5-10% of all hypertensive patients, and clearly above the estimated prevalence in the past."	2.43	[Modern pharmacological aspects of hyperaldosteronism therapy]. ( Quinkler, M; Reincke, M, 2006)
"Eplerenone has the advantage, compared with spironolactone, to be better tolerated in terms of "hormonal" adverse effects."	2.43	[The revived interest in aldosterone antagonists]. ( Waeber, B, 2006)
"Aldosterone has direct effects on the vasculature and has been associated with vascular smooth muscle cell hypertrophy, endothelial dysfunction, cardiac fibrosis, proteinuria, and renal vascular injury."	2.42	Aldosterone: a risk factor for vascular disease. ( Fritsch Neves, M; Schiffrin, EL, 2003)
"Hyperaldosteronism in its various forms is a recognized secondary cause of hypertension, yet the frequency of these disorders and the appropriate evaluation of suspected patients remain controversial."	2.42	Aldo is back: recent advances and unresolved controversies in hyperaldosteronism. ( Auchus, RJ, 2003)
"Primary aldosteronism (PA) has been regarded for a long time as being a rare cause of arterial hypertension, but its prevalence has recently been reassessed as about 10%."	2.42	[Investigation of hyperaldosteronism in the hypertensive patient. Why? When? How?]. ( Amar, J; Chamontin, B; Herpin, D; Sosner, P, 2003)
"Eplerenone is a selective aldosterone receptor blocker that displays little interaction with androgen and progesterone receptors."	2.42	Eplerenone: a selective aldosterone blocker. ( Stier, CT, 2003)
"Aldosterone is an important and independent target for therapeutic intervention in hypertension and hypertension-related diseases."	2.42	Aldosterone receptor antagonists for hypertension: what do they offer? ( Krum, H; Liew, D, 2003)
"Hypertension is a significant risk factor for vascular complications of diabetes, and the target blood pressure in patients with diabetes or chronic renal disease and hypertension should be lower than that in patients with hypertension alone."	2.42	New developments in the management of hypertension. ( Gay, C; Gunning, K; Magill, MK; Saffel-Shrier, S, 2003)
"Heart failure is also a major cause of hospital admissions; its amelioration and, as far as possible, prevention is therefore important in terms not only of morbidity and premature mortality for the individual patient, but also containment of healthcare costs."	2.42	The role of mineralocorticoid receptor antagonists in the treatment of cardiac failure. ( Funder, JW, 2003)
"Eplerenone is a newer aldosterone antagonist that is much more selective, with minimal affinity for progesterone and androgenic receptors; therefore, there are very few reports of adverse sexual effects."	2.42	Eplerenone in hypertension. ( Burgess, E, 2004)
"Aldosterone plays an important role in the pathogenesis of cardiovascular and renal disease that is independent of angiotensin II."	2.42	Pleiotropic actions of aldosterone and the effects of eplerenone, a selective mineralocorticoid receptor antagonist. ( Takeda, Y, 2004)
"Eplerenone is a selective aldosterone blocker."	2.41	Eplerenone--a novel selective aldosterone blocker. ( Carter, BL; Zillich, AJ, 2002)
" Although we have previously demonstrated aldosterone escape during long term administration of AT1 antagonist, pathological significance of aldosterone remains unknown."	2.41	[Significance of combining spironolactone during long-term administration of ARB]. ( Naruse, M; Sato, A; Takagi, S; Takano, K; Tanabe, A; Tsuchiya, K, 2002)
"Aldosterone has been identified as a critically important neurohormone with direct detrimental effects on the myocardium."	2.41	Angiotensin receptor blockers and aldosterone antagonists in chronic heart failure. ( Miller, AB; Srivastava, P, 2001)
" Pharmacokinetic studies reveal that eplerenone has good bioavailability with low protein binding, good plasma exposure, and is highly metabolized to inactive metabolites and excreted principally in the bile."	2.41	Eplerenone: a selective aldosterone receptor antagonist (SARA). ( Cook, CS; Delyani, JA; Levin, S; Rocha, R; Roniker, B; Sing, YL; Tobert, DS; Whelihan, B; Workman, DL, 2001)
"Spironolactone has been found to increase life expectancy and to reduce hospitalisation frequency when added to the conventional therapeutic regimen of patients with advanced congestive heart failure and systolic dysfunction."	2.41	Diuretics in the treatment of patients who present congestive heart failure and hypertension. ( Reyes, AJ, 2002)
"Spironolactone has a lesser effect on lipids than do thiazides."	2.37	Effects of diuretic drugs on the lipid profile. ( Ames, R, 1988)
" Suitable techniques for the investigation of secondary aldosteronism of unknown cause and for primary and secondary hypoaldosteronism are described, as well as the adjustment of dosage for replacement therapy where mineralocorticoid secretion is deficient."	2.37	Disorders of mineralocorticoid activity. ( Drury, PL, 1985)
"Although true treatment resistant hypertension is relatively rare (about 7."	1.91	Results of the trycort: Cohort study of add-on antihypertensives for treatment of resistant hypertension. ( Anđelković, B; Cvjetan, R; Gocić Petrović, R; Janković, SM; Kostić, T; Petrović, M; Radovanović, S; Ratković, N; Rihor, B; Spiroski, D; Stanković, A; Stojković, S; Zdravković, M, 2023)
"Primary aldosteronism is the underlying cause of hypertension in primary care settings in approximately 6% of cases, and it is even more common in patients with resistant hypertension."	1.91	Primary Aldosteronism. ( Quencer, KB; Rugge, JB; Senashova, O, 2023)
"Newly presenting hypertension is much the same-hold off on first-order antihypertensive(s) and prescribe spironolactone 25 mg/day for 4 weeks."	1.91	Who and How Should We Screen for Primary Aldosteronism? ( Funder, JW, 2023)
"Spironolactone was initiated."	1.72	Apparent mineralocorticoid excess: A diagnosis beyond classical causes of severe hypertension in a child. ( Baltu, D; Çelik Ertaş, NB; Duzova, A; Gönç, N; Gulhan, B; Ozcan, HN; Özdemir, G; Ünsal, Y; Utine, E, 2022)
"Refractory hypertension (RfHT) and obstructive sleep apnea (OSA) share common pathophysiological mechanisms and probably are intrinsically associated, but their prevalence, clinical profile, and polysomnography (PSG) pattern remain misunderstood."	1.72	Prevalence and associated factors of obstructive sleep apnea in refractory hypertension. ( Cavalcanti, AH; Chedier, B; de Souza, F; Muxfeldt, ES; Roderjan, CN, 2022)
"Aldosterone was given for the last 4 months."	1.72	Effect of Metabolic Adaptation by Voluntary Running Wheel Activity and Aldosterone Inhibition on Renal Function in Female Spontaneously Hypertensive Rats. ( Atmanspacher, F; Grgic, I; Schlüter, KD; Schreckenberg, R; Wolf, A, 2022)
"Increased fibrosis was accompanied by myofibroblast and macrophage infiltration in the heart and the kidney."	1.62	The effect of spironolactone on cardiac and renal fibrosis following myocardial infarction in established hypertension in the transgenic Cyp1a1Ren2 rat. ( Leader, CJ; Walker, RJ; Wilkins, GT, 2021)
"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)
"We can treat hypertension more effectively by getting the blood pressure measurement right, understanding the link between albuminuria and hypertension, enabling the use of spironolactone to treat resistant hypertension through the use of drugs that bind potassium in the gut, and addressing the structural determinants of health."	1.51	Caring for individuals with hypertension in CKD, especially those with low education. ( Agarwal, R, 2019)
"Hypertension was reported in 70-92% of patients, irrespective of disease cohort or population."	1.51	Patient characteristics and initiation of mineralocorticoid receptor antagonists in patients with chronic kidney disease in routine clinical practice in the US: a retrospective cohort study. ( Blankenburg, M; Eisenring, S; Fett, AK; Gay, A; Haas, G, 2019)
"Spironolactone is an effective antihypertensive drug, especially for patients with resistant hypertension, and is considered by the World Health Organization as an essential medication."	1.48	Pannexin 1 Channels as an Unexpected New Target of the Anti-Hypertensive Drug Spironolactone. ( Barrett, E; Bayliss, DA; Butcher, JT; Chiu, YH; DeLalio, LJ; Desai, BN; Good, ME; Isakson, BE; Jaffe, IZ; Leitinger, N; Lohman, AW; Lorenz, UM; Medina, CB; Mendu, SK; Poon, IKH; Ravichandran, KS, 2018)
"Primary aldosteronism is associated with high cardiovascular morbidity and mortality due to activation of cardiac mineralocorticoid receptors."	1.48	Systolic heart failure in a patient with primary aldosteronism. ( Alvarez, C; Mohan, V, 2018)
"Venous thrombosis was induced by vena cava ligation."	1.48	Beneficial effect of combined spironolactone and quinapril treatment on thrombosis and hemostasis in 2K1C hypertensive rats. ( Aleksiejczuk, M; Chabielska, E; Gromotowicz-Poplawska, A; Marcinczyk, N; Mikita, J; Stankiewicz, A; Szemraj, J, 2018)
"Spironolactone treatment resulted in decreased blood pressure and rise in serum potassium levels."	1.46	Apparent mineralocorticoid excess and the long term treatment of genetic hypertension. ( Khattab, A; New, MI; Razzaghy-Azar, M; Yau, M, 2017)
"Eplerenone treatment of patients with PA reduces blood pressure, increases serum potassium level, and improves vascular status."	1.43	Eplerenone improves carotid intima-media thickness (IMT) in patients with primary aldosteronism. ( Anzai, K; Kawate, H; Matsuda, Y; Matsuzaki, C; Nomura, M; Ohnaka, K; Sakamoto, R; Shibue, K; Takayanagi, R, 2016)
"Aggressive treatment of hypertension resulted in complete resolution of the clinical and radiologic features of the syndrome."	1.43	Does this patient have hypertensive encephalopathy? ( Argyropoulou, MI; Christopoulou, F; Elisaf, M; Kosta, P; Rizos, EC, 2016)
"Hypertension is attributed to sodium retention in the distal nephron, but 11βHSD2 is also expressed in the brain."	1.43	Conditional Deletion of Hsd11b2 in the Brain Causes Salt Appetite and Hypertension. ( Al-Dujaili, EA; Bailey, MA; Christensen, TH; Evans, LC; Holmes, MC; Ivy, JR; Kenyon, CJ; McNairn, JA; Menzies, RI; Mullins, JJ; Seckl, JR; Wyrwoll, C, 2016)
"Hypertension is often associated with metabolic syndrome (MetS), and serves as a risk factor of MetS and its complications."	1.43	Eplerenone restores 24-h blood pressure circadian rhythm and reduces advanced glycation end-products in rhesus macaques with spontaneous hypertensive metabolic syndrome. ( Ding, Y; Hou, N; Hu, X; Li, C; Liu, Y; Ma, D; Mao, J; Peng, Y; Shang, H; Sun, X; Wang, C; Wang, J; Xiao, RP; Xiao, Y; Zeng, F; Zhang, J; Zhang, X; Zhang, Y; Zheng, W, 2016)
"Treatment of primary aldosteronism (PA) aims at preventing or correcting hypertension, hypokalemia and target organ damage."	1.43	SFE/SFHTA/AFCE consensus on primary aldosteronism, part 6: Adrenal surgery. ( Amar, L; Chaffanjon, P; Kraimps, JL; Ménégaux, F; Steichen, O; Zinzindohoue, F, 2016)
"Echocardiography showed 73% dilated cardiomyopathy; 83% showed moderate to severe LV systolic dysfunction (mean EF 36."	1.43	Clinical and echocardiographic characteristics and outcomes in congestive heart failure at the Hospital of The State University of Haiti. ( Malebranche, R; Morisset, PH; Raphael, NA; Tabou Moyo, C; Wilentz, JR, 2016)
"Primary aldosteronism (PA), the most common form of secondary hypertension, causes relevant morbidity."	1.43	The Clinical Value of Salivary Aldosterone in Diagnosis and Follow-Up of Primary Aldosteronism. ( Asbach, E; Bidlingmaier, M; Fourkiotis, V; Gerum, S; Lichtenauer, UD; Manolopoulou, J; Quinkler, M; Reincke, M, 2016)
"This agent could be useful for the treatment of hypertension, cardiovascular and renal disorders."	1.42	Pharmacological profile of CS-3150, a novel, highly potent and selective non-steroidal mineralocorticoid receptor antagonist. ( Aoki, K; Arai, K; Homma, T; Ishikawa, H; Mizuno, M; Morikawa, Y; Sada, T; Tsuruoka, H; Ubukata, N, 2015)
"In experimental hyperaldosteronism, the increase in Gal-3 expression was associated with cardiac inflammation and fibrosis, alterations that were prevented by Gal-3 blockade independently of blood pressure levels."	1.42	Galectin-3 blockade inhibits cardiac inflammation and fibrosis in experimental hyperaldosteronism and hypertension. ( Cachofeiro, V; Calvier, L; Fernández-Celis, A; Jaisser, F; Jurado-López, R; López-Andrés, N; Martínez-Martínez, E; Rossignol, P; Rossoni, LV; Rousseau, E; Zannad, F, 2015)
" 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)
"Spironolactone treatment prevented Th17 cell activation and increased numbers of forkhead box P3-positive cells relative to DOCA-salt rats."	1.40	Spironolactone decreases DOCA-salt-induced organ damage by blocking the activation of T helper 17 and the downregulation of regulatory T lymphocytes. ( Alzamora, R; Amador, CA; Barrientos, V; Carrasco, L; Figueroa, F; González, M; Herrada, AA; Kalergis, AM; Michea, L; Peña, J; Valdés, S, 2014)
"Canrenone is a derivative of spironolactone with lower antiandrogen activity."	1.40	Aldosterone receptor blockers spironolactone and canrenone: two multivalent drugs. ( Armanini, D; Bordin, L; Clari, G; Donà, G; Sabbadin, C, 2014)
"Spironolactone treatment caused a very small reduction in the damage caused by permanent focal cerebral ischemia."	1.40	Temporary mineralocorticoid receptor antagonism during the development of hypertension improves cerebral artery dilation. ( Dorrance, AM; McClain, JL, 2014)
"Corticosterone or vehicle was injected twice daily in rats from 8 to 12 weeks of age."	1.39	Glucocorticoid-induced hypertension and cardiac injury: effects of mineralocorticoid and glucocorticoid receptor antagonism. ( Hattori, T; Iwase, E; Miyachi, M; Murase, T; Murohara, T; Nagata, K; Ohtake, M; Takahashi, K; Tsuboi, K, 2013)
"The spironolactone treatment group demonstrated significant increases in heart rate and cardiac output and a decrease in cardiac index compared to SHR controls."	1.39	Echocardiographic effects of eplerenone and aldosterone in hypertensive rats. ( Dostal, DE; Jewell, C; Song, J; Watson, LE, 2013)
"In patients with congestive heart failure (CHF), use of loop diuretic therapy may result in acute kidney insufficiency (AKI)."	1.39	Predisposing factors for acute kidney injury in Hispanic patients treated with diuretics for decompensated heart failure. ( Cangiano, JL; López, JE; Marmorato, R; Pagán, P; Ramírez, T; Ricci, F; Soto-Salgado, M; Vega, J, 2013)
"Spironolactone treatment (25mg/day) was added and was well tolerated, with no change in renal function and kaliemia within normal (4."	1.39	Resistant hypertension. ( Armario, P; de la Sierra, A; Oliveras, A, 2013)
"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)
"Hypertension is a major risk factor for the development and progression of chronic kidney disease (CKD)."	1.38	Long-term effects of aldosterone blockade in resistant hypertension associated with chronic kidney disease. ( Acelajado, MC; Calhoun, DA; Cartmill, FR; Cofield, SS; Dell'Italia, LJ; Dudenbostel, T; Oparil, S; Pisoni, R, 2012)
"Aldosterone (Aldo) is an important active hormone in the renin-angiotensin-aldosterone system and plays a vital role in the development of hypertension, heart failure and other cardiovascular diseases."	1.38	Endogenous aldosterone is involved in vascular calcification in rat. ( Cai, Y; Jia, LX; Qi, YF; Tang, CS; Wang, X; Wu, SY; Xiao, CS; Yu, YR, 2012)
"Spironolactone treatment significantly increased aldosterone levels in males and females independent of the sodium content of the diet."	1.38	Sex-specific effects of spironolactone on blood pressure in gonadectomized male and female Wistar rats. ( Bartel, C; Götz, F; Hofmann, PJ; Kienitz, T; Michaelis, M; Quinkler, M, 2012)
"Hyperaldosteronism combined with hypertension favored the macrophage infiltration (CD68(+) cells) in heart, and enhanced the mRNA level of monocyte chemoattractant protein 1, osteopontin, and galectin 3."	1.38	Aldosterone inhibits antifibrotic factors in mouse hypertensive heart. ( Azibani, F; Benard, L; Carrier, L; Chatziantoniou, C; Delcayre, C; Fazal, L; Launay, JM; Merval, R; Polidano, E; Samuel, JL; Schlossarek, S; Tournoux, F, 2012)
"Hypertension was evident by the second day of treatment, being preceded by reduced renal sodium excretion due to activation of the thiazide-sensitive sodium-chloride co-transporter."	1.38	Activation of thiazide-sensitive co-transport by angiotensin II in the cyp1a1-Ren2 hypertensive rat. ( Ashek, A; Bailey, MA; Bellamy, CO; Flatman, PW; Harmar, AJ; Kenyon, CJ; Menzies, RI; Mullins, JJ; Mullins, LJ, 2012)
"Treatment with eplerenone markedly decreased the gene expression and reduced the albuminuria and renal morphological changes."	1.37	Effects of mineralocorticoid receptor blockade on glucocorticoid-induced renal injury in adrenalectomized rats. ( Fujisawa, Y; Hitomi, H; Ihara, G; Kiyomoto, H; Kobori, H; Kohno, M; Nagai, Y; Nakano, D; Nishiyama, A; Ohashi, N; Rafiq, K, 2011)
"Hypertension is well known to increase atrial fibrillation (AF) and the development of AF is associated with atrial chamber remodeling."	1.37	Role of mineralocorticoid receptor on atrial structural remodeling and inducibility of atrial fibrillation in hypertensive rats. ( Aizawa, Y; Chinushi, M; Ding, L; Hanawa, H; Hoyano, M; Ito, M; Kimura, S; Kodama, M; Obata, H; Tomita, M, 2011)
"Kidney impairment is noted in primary aldosteronism (PA), and probably initiated by glomerular hyperfiltration."	1.37	Kidney impairment in primary aldosteronism. ( Chang, HW; Cheng, BW; Chiang, CK; Chiu, JS; Chu, TS; Chueh, SC; Ho, YL; Hu, FC; Huang, KH; Kuo, CC; Lin, CY; Lin, JW; Lin, LY; Lin, SL; Lin, YH; Liu, KL; Tsai, CT; Wang, SM; Wu, KD; Wu, VC; Yang, SY; Yen, RF, 2011)
"Eplerenone treatment significantly reduced mean 24-h systolic/diastolic BP levels (143/80 mmHg to 132/74 mmHg, both p < 0."	1.37	Efficacy of eplerenone added to renin-angiotensin blockade in elderly hypertensive patients: the Jichi-Eplerenone Treatment (JET) study. ( Hoshide, S; Kanemaru, Y; Kario, K; Nagata, M; Sasaki, K; Shimada, K; Tamaki, N; Yano, Y, 2011)
"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)
"Resistant hypertension has evolved as an important global health care problem."	1.37	What is the role of aldosterone excess in resistant hypertension and how should it be investigated and treated? ( Sica, DA, 2011)
"Spironolactone treatment did not alter SBP."	1.36	The glucocorticoid receptor is required for experimental adrenocorticotrophic hormone-induced hypertension in mice. ( Cole, TJ; McKenzie, KU; Schyvens, CG; Vickers, JJ; Whitworth, JA; Zhang, Y, 2010)
" The cause of hyperkalemia was considered to be several doses of spiranolactone, an aldosterone antagonist, in addition to the long-term intake of ramipril, an ACE inhibitor."	1.36	Syncope caused by hyperkalemia during use of a combined therapy with the angiotensin-converting enzyme inhibitor and spironolactone. ( Erden, I; Ozhan, H; Yalcin, S, 2010)
"Aldosterone promotes renal fibrosis via the mineralocorticoid receptor (MR), thus contributing to hypertension-induced nephropathy."	1.35	Hypertension-induced renal fibrosis and spironolactone response vary by rat strain and mineralocorticoid receptor gene expression. ( Camp, JR; Cavallari, LH; Fashingbauer, LA; Geenen, DL; King, ST, 2008)
"Treatment with eplerenone in Dahl salt-sensitive rats was associated with significant improvements in kidney to body weight ratio, urinary protein excretion and renal injury scores and decreased renal (pro)renin receptor protein expression and angiotensinogen and AT1R mRNA levels and kidney Ang II content."	1.35	Effect of mineralocorticoid receptor blockade on the renal renin-angiotensin system in Dahl salt-sensitive hypertensive rats. ( Demura, M; Karashima, S; Takeda, Y; Usukura, M; Yamagishi, M; Yoneda, T; Zhu, A, 2009)
"Primary aldosteronism (PA) is the most common secondary cause of hypertension that has recently been implicated in alterations of the immune system and progression of cardiovascular disease."	1.35	Primary aldosteronism can alter peripheral levels of transforming growth factor beta and tumor necrosis factor alpha. ( Carvajal, CA; Castillo, CR; Contreras, FJ; Fardella, CE; Herrada, AA; Kalergis, AM; Mosso, LM; Stehr, CB, 2009)
"Spironolactone treatment decreased collagen content in the media of thoracic aortas from prehypertensive SHR, whereas losartan decreased collagen content in the media of aortas from hypertensive SHR."	1.35	Changes in the composition of the thoracic aortic wall in spontaneously hypertensive rats treated with losartan or spironolactone. ( Che, ZQ; Gao, PJ; Han, WQ; Liu, JJ; Wu, LY; Wu, YJ; Zhang, J; Zhou, HY; Zhu, DL, 2009)
"The hypertension was not different and virtually superimposable in WT vs."	1.35	The role of aldosterone in mediating the dependence of angiotensin hypertension on IL-6. ( Brands, MW; Cannon, JG; Schreihofer, DA; Sturgis, LC, 2009)
"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)
"Resistant hypertension is defined as blood pressure (BP) that remains uncontrolled in spite of the use of >/=3 antihypertensive medications."	1.35	Mechanisms and treatment of resistant hypertension. ( Gaddam, KK; Oparil, S; Pimenta, E, 2008)
"Primary hyperaldosteronism is a rare (<1%) and underdiagnosed cause of secondary hypertension."	1.34	Is primary hyperaldosteronism a risk factor for aortic dissection? ( Ahmed, SH; Husain, NM; Khawaja, SN; Massey, CV; Pettyjohn, FS, 2007)
"Treatment of primary aldosteronism decreased blood pressure (BP) and restored normal potassium concentrations."	1.34	Renal cysts and hypokalemia in primary aldosteronism: results of long-term follow-up after treatment. ( Baroselli, S; Bazzocchi, M; Catena, C; Chiuch, A; Colussi, GL; Lapenna, R; Nadalini, E; Novello, M; Sechi, LA, 2007)
"Primary aldosteronism (PA) is the most common secondary cause of hypertension and recently has been implicated as a cause of impaired glucose tolerance."	1.34	A possible association between primary aldosteronism and a lower beta-cell function. ( Artigas, RA; Carvajal, CA; Castillo, CR; Fardella, CE; Maiz, A; Mosso, LM; Ortiz, EH, 2007)
"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)
"Spironolactone is an effective therapy for BAH and it is an adequate option for APA treatment when an adrenalectomy is not viable."	1.33	[Primary aldosteronism: analysis of a series of 54 patients]. ( Aliaga, L; Fernández-Torres, C; Jaén, F; Jiménez-Alonso, J; Mediavilla-García, JD; Sabio, JM, 2005)
"Hyperkalemia is a complications of the use of angiotensin converting enzyme inhibitors, angiotensin receptor antagonists and aldosterone antagonists."	1.33	[Severe hyperkalemia associated to the use of losartan and spironolactone: case report]. ( Kauffmann, R; Orozco, R; Venegas, JC, 2005)
"Sixty-four patients with primary aldosteronism were included in the study."	1.33	Diurnal blood pressure pattern in patients with primary aldosteronism. ( Elenkova, A; Kalinov, K; Nachev, E; Orbetzova, M; Schigarminova, R; Stoynev, A; Yaneva, M; Zacharieva, S, 2006)
"Of these, 585 (76."	1.33	Use and side-effect profile of spironolactone in a private cardiologist's practice. ( Karambelas, MR; Katholi, RE; Williams, EM, 2006)
"Patients with primary aldosteronism were compared with 100 patients with essential hypertension, matched for severity and duration of hypertension."	1.33	Long-term renal outcomes in patients with primary aldosteronism. ( Baroselli, S; Catena, C; Colussi, GL; Lapenna, R; Nadalini, E; Novello, M; Sechi, LA, 2006)
"The incidence of primary aldosteronism in patients with difficult to treat hypertension is higher than previously stated in texts."	1.32	[Treatment refractory hypertension with atrophic kidney: attending to one and not neglecting the other]. ( Guertler, M; Suter, PM; Vetter, W, 2003)
"Primary hyperaldosteronism (PH) is frequently considered to be a secondary form of diabetes mellitus (DM)."	1.32	Does the treatment of primary hyperaldosteronism influence glucose tolerance? ( Sindelka, G; Skrha, J; Strauch, B; Widimský, J, 2003)
"Thus aldosterone and salt treatment in uninephrectomized rats led to severe hypertension and the development of a vascular inflammatory phenotype in the heart, which may represent one mechanism by which aldosterone contributes to myocardial disease."	1.31	Aldosterone induces a vascular inflammatory phenotype in the rat heart. ( Blomme, EA; Delyani, JA; Frierdich, GE; Kekec, BK; McMahon, EG; Nachowiak, DA; Rocha, R; Rudolph, AE, 2002)
"Spironolactone prevented cardiac hypertrophy in adrenalectomized SHRSP."	1.31	Cardiac aldosterone production in genetically hypertensive rats. ( Demura, M; Mabuchi, H; Miyamori, I; Takeda, Y; Yoneda, T, 2000)
"Liddle's syndrome is a rare form of autosomal-dominant salt-sensitive hypertension."	1.31	A family with liddle's syndrome caused by a mutation in the beta subunit of the epithelial sodium channel. ( Kitamura, K; Kyuma, M; Sasaki, S; Shimamoto, K; Takeuchi, H; Takizawa, H; Tomita, K; Torii, T; Ura, N, 2001)
"Primary aldosteronism is a common cause of non-renal secondary hypertension."	1.31	Normokalemic hyperaldosteronism in patients with resistant hypertension. ( Benchetrit, S; Bernheim, J; Podjarny, E, 2002)
"Only when the Cushing syndrome has been confirmed clinically and biochemically, should an imaging procedure be performed."	1.31	[Secondary forms of hypertension. 5. Hypertension caused by Cushing syndrome and Conn's disease]. ( Füessl, HS, 2002)
"DOCA-salt hypertension was induced in 8-wk-old male Wistar rats by uninephrectomy and administration of DOCA (25 mg every fourth day, subcutaneously) and 1% NaCl in the drinking water for 4 wk."	1.30	Reversal of cardiac fibrosis in deoxycorticosterone acetate-salt hypertensive rats by inhibition of the renin-angiotensin system. ( Brown, L; Duce, B; Miric, G; Sernia, C, 1999)
"Glucocorticoid-remediable aldosteronism (GRA) is a rarely recognised cause of arterial hypertension."	1.30	Abolished nocturnal blood pressure fall in a boy with glucocorticoid-remediable aldosteronism. ( Bernhardt, R; Hampf, M; Seeman, T; Widimský, J, 1999)
"Spironolactone treatment (50 mg/kg per day) for 7 days in deficient rats restored blood pressure and heart rate to normal levels and significantly reduced sodium levels in erythrocytes and cerebrospinal fluid."	1.29	Hypertension induced by a nonpressor dose of angiotensin II in kininogen-deficient rats. ( Katori, M; Kuribayashi, Y; Majima, M; Mizogami, S; Oh-ishi, S, 1994)
"Spironolactone treatment (100 mg/daily) completely reversed the syndrome of mineralocorticoid excess."	1.29	Unilateral adrenal hypersecretion of both aldosterone and cortisol in two first cousins with a syndrome of mineralocorticoid excess but without signs of hypercortisolism. ( Balsano, F; Bonavita, MS; Carlomagno, A; Coassin, S; De Siati, L; Falaschi, P; Ferri, C; Gualdi, G, 1994)
"Spironolactone, however, was able to prevent myocardial fibrosis in RHT and aldosterone models of acquired arterial hypertension irrespective of the development of LVH and the presence of hypertension."	1.29	Antifibrotic effects of spironolactone in preventing myocardial fibrosis in systemic arterial hypertension. ( Brilla, CG; Matsubara, LS; Weber, KT, 1993)
" Chronic administration of spironolactone prevented the development of hypertension but failed to prevent other adaptive physiological changes characteristically occurring during exposure to cold and seen in the cold-treated control rats."	1.28	Effect of chronic treatment with clonidine and spironolactone on cold-induced elevation of blood pressure. ( Baron, A; Fregly, MJ; Riesselmann, A, 1991)
"Hyperlipidemia is prevalent in hypertension, but the cause of this association is unknown."	1.28	Hyperlipidemia in hypertension: causes and prevention. ( Ames, RP, 1991)
" Long-term administration of spironolactone, beta blockers, or a beta-blocker/dihydralazine combination to hypertensive patients sufficiently reduced systolic and diastolic blood pressure to about the same extent; however, only spironolactone had any effect on piezoelectric indexes of arterial elasticity."	1.28	Peripheral action of spironolactone: improvement in arterial elasticity. ( Ansquer, JC; Lagrue, G; Meyer-Heine, A, 1990)
"Aldosterone treatment resulted in an increase in blood pressure to 165 +/- 5 mmHg over the control value of 105 +/- 2 mmHg within 3 wk of experimental period."	1.28	Effects of antimineralocorticoid RU 26752 on steroid-induced hypertension in rats. ( Agarwal, M; Corley, K; Kalimi, M; Opoku, J, 1990)
"Spironolactone treatment normalized the arterial pressure in patients with primary aldosteronism at all Na intakes."	1.27	Effect of spironolactone on fluid volumes and adrenal steroids in primary aldosteronism. ( Hirano, Y; Ichikawa, S; Kogure, M; Matsuo, H; Murata, K; Sakamaki, T; Tajima, Y; Yagi, S, 1984)
"As spironolactone can cause gastric irritation, the present findings support the recommendation that spironolactone always be prescribed for once-daily intake together with breakfast."	1.27	Influence of food intake on antihypertensive drugs: spironolactone. ( Liedholm, H; Lindholm, L; Melander, A; Thulin, T; Wåhlin-Boll, E, 1983)
"Treatment of hypertension is best accomplished in stepwise fashion, beginning with nondrug therapy followed by a knowledgeable selection of antihypertensive drugs."	1.27	Current management of hypertension. ( Moore, MA, 1985)
"Treatment with spironolactone alone for 2 months corrected hypertension, hypokalemic alkalosis, and all laboratory and radiologic evidence of rickets and hyperparathyroidism, resulting in acceleration of growth rate."	1.27	Spironolactone-reversible rickets associated with 11 beta-hydroxysteroid dehydrogenase deficiency syndrome. ( Arnhold, IJ; Batista, MC; Bloise, W; Kater, CE; Mendonça, BB; Nicolau, W; Rocha, A, 1986)
"Biological primary aldosteronism was found post-operatively in 2 of these 3 patients and also in one whose hypertension was improved."	1.27	[Results of the surgical treatment of Conn's adenomas]. ( Chatellier, G; Corvol, P; Duclos, JM; Ménard, J; Pagny, JY; Plouin, PF, 1987)
"Spironolactone was prescribed at a mean dose of 98 mg, hydrochlorothiazide at 36 mg and cyclothiazide at 2 mg, during a mean follow-up of 20 months."	1.27	Long-term metabolic effects of spironolactone and thiazides combined with potassium-sparing agents for treatment of essential hypertension. ( Charru, A; Chatellier, G; Corvol, P; Degoulet, P; Jeunemaitre, X; Julien, J; Ménard, J; Plouin, PF, 1988)
"Additional evidence suggests that sudden death may occasionally result from this VEA."	1.27	Potassium loss, ventricular irritability, and the risk of sudden death in hypertensive patients. ( Holland, OB, 1986)
" Initial dosage of two tablets could be reduced to one tablet daily following normalization (less than 90 mm Hg) of diastolic blood pressure in one third of patients."	1.27	[Treatment of medium-severe essential hypertension with beta-Aldopur under practice conditions]. ( Guberner, G; Hitzenberger, G; Nitsch-Fitz, R; Rheindorf, H; Tutsch, G; Ziegler, KT, 1985)
"Thus, the present case of pseudoaldosteronism was attributed to Jintan, and raises a caution to excessive Jintan ingestion."	1.26	A case of pseudoaldosteronism due to addiction of Jintan, a mouth refresher popular among Japanese. ( Arakawa, K; Kamei, H, 1982)
"True refractory hypertension is relatively rare, but the causes of pseudoresistance are many."	1.26	Management of the patient with resistant hypertension. ( Tarazi, RC, 1981)
"Spironolactone was indicated preoperatively for all surgical candidates, for non-operated APA patients, and for all IHA patients."	1.26	Primary aldosteronism -- screening, diagnosis and therapy. ( Gregorová, I; Horký, K; Hradec, E; Silinková-Málková, E; Vancura, J, 1981)
"Amiloride was disproportionately potent in lowering serum bicarbonate, and the data do not suggest that these drugs elevate plasma potassium simply by correcting metabolic alkalosis."	1.26	Amiloride, spironolactone, and potassium chloride in thiazide-treated hypertensive patients. ( Fraser, R; Hettiarachchi, J; Morton, JJ; Ramsay, LE, 1980)
"Hyperparathyroidism and hyperaldosteronism coexisted in association with medullary sponge kidneys in a 27-year-old woman with severe hypertension."	1.26	Hyperaldosteronism, hyperparathyroidism, medullary sponge kidneys, and hypertension. ( Hellman, DE; Kartchner, M; Komar, N; Mayes, D; Pitt, M, 1980)
"Renal disease and hypertension is a continuing challenge to the nephrologist."	1.26	The kidney and antihypertensive therapy. ( Bailey, RR, 1976)
" The data shows that this dosage of spironolactone gave minor adjustments of the systemic and renal circulation in spite of the consistent changes in BW, PV, PRA and PA."	1.26	Haemodynamic effects of treatment and withdrawal of spironolactone in essential hypertension. ( Falch, DK; Johansson, R; Norman, N; Odegaard, AE, 1979)
"Triamterene was administered in a dose of 100 mg/day for 8 days to 7 patients with essential hypertension."	1.26	Effect of triamterene on urinary excretion of immunoreactive prostaglandin E in essential hypertension. ( Abe, K; Chiba, S; Irokawa, N; Ito, T; Otsuka, Y; Saito, K; Sakurai, Y; Sato, M; Yasujima, M; Yoshinaga, K, 1979)
"Treatment with spironolactone did not significantly alter the natriuretic response of the spontaneously hypertensive rats (43 +/- 8 mueq/h) to another salt load, but increased the natriuretic response of the normotensive rats (55 +/- 7 mueq/h) to that of the hypertensive rats."	1.26	Aldosterone in the exaggerated natriuresis of spontaneously hypertensive rats. ( Bauer, JH; Willis, LR, 1978)
"Twenty patients suffering from primary hyperaldosteronism were studied."	1.26	[The renin-angiotensin-aldosterone system in hypertensive patients. II. Diagnosis of primary hyperaldosteronism]. ( Benguigui, L; Corvol, P; Houde, M; Menard, J; Milliez, P; Tonnelier, M, 1977)
"In spironolactone-treated rats blood pressure and total aortic renin concentrations were comparable with those in the control rats."	1.26	Effects of aldosterone and spironolactone on arterial renin in rats. ( Rosenthal, J, 1976)
"Adequate treatment of hypertension requires that the physician understand the pharmacologic actions of antihypertensive agents."	1.25	Current therapy of hypertension. A pharmacologic approach. ( Goldberg, LI, 1975)
"Indapamide has a prolonged saluretic action which in combination with the direct vascular effects may well account for its antihypertensive activity."	1.25	Antihypertensive action of indapamide. Comparative studies in several experimental models. ( Kyncl, J; Oheim, K; Seki, T; Solles, A, 1975)

Research

Studies (1,181)

Authors

Clinical Trials (41)

Trial Overview

Trial Outcomes

Change in AOBP SBP From Baseline to Week 12 or Last Available AOBP SBP Prior to Addition of Any New BP Medications or Increase From Any Baseline BP Medications

Timeframe	Studies, this research(%)	All Research%
pre-1990	480 (40.64)	18.7374
1990's	61 (5.17)	18.2507
2000's	279 (23.62)	29.6817
2010's	306 (25.91)	24.3611
2020's	55 (4.66)	2.80

Authors	Studies
Meyers, MJ	1
Arhancet, GB	1
Hockerman, SL	1
Chen, X	3
Long, SA	1
Mahoney, MW	1
Rico, JR	1
Garland, DJ	1
Blinn, JR	1
Collins, JT	1
Yang, S	1
Huang, HC	1
McGee, KF	1
Wendling, JM	1
Dietz, JD	1
Payne, MA	1
Homer, BL	1
Heron, MI	1
Reitz, DB	1
Hu, X	3
Piotrowski, DW	1
Hasui, T	1
Ohyabu, N	1
Ohra, T	1
Fuji, K	1
Sugimoto, T	1
Fujimoto, J	1
Asano, K	1
Oosawa, M	1
Shiotani, S	1
Nishigaki, N	1
Kusumoto, K	1
Matsui, H	5
Mizukami, A	1
Habuka, N	1
Sogabe, S	1
Endo, S	1
Ono, M	1
Siedem, CS	1
Tang, TP	1
Gauthier, C	1
De Meese, LA	1
Boyd, SA	1
Fukumoto, S	1
An, J	1
Niu, F	1
Sim, JJ	1
Moore, MN	1
Schultz, MG	1
Hare, JL	2
Marwick, TH	3
Sharman, JE	3
Orlova, YA	1
Begrambekova, YL	1
Plisuk, AG	1
Thangaraj, SS	1
Oxlund, CS	4
Fonseca, MPD	1
Svenningsen, P	2
Stubbe, J	1
Palarasah, Y	1
Ketelhuth, DFJ	1
Jacobsen, IA	6
Jensen, BL	3
Leader, CJ	3
Wilkins, GT	2
Walker, RJ	3
Agarwal, R	10
Gulhan, B	1
Ünsal, Y	1
Baltu, D	1
Çelik Ertaş, NB	1
Özdemir, G	1
Utine, E	1
Ozcan, HN	1
Duzova, A	1
Gönç, N	1
Rossignol, P	9
Budden, J	1
Mayo, MR	5
Arthur, S	4
Williams, B	9
White, WB	8
Bao, M	1
Song, Y	1
Wu, S	1
Li, J	2
Nikrýnová Nguyen, TMP	1
Štrauch, B	6
Petrák, O	5
Krátká, Z	3
Holaj, R	5
Kurcová, I	1
Marešová, V	1
Pilková, A	1
Hartinger, J	1
Waldauf, P	4
Zelinka, T	5
Widimský, J	9
Forestiero, V	1
Sconfienza, E	1
Mulatero, P	3
Monticone, S	1
Koch, V	1
Gruenewald, LD	1
Gruber-Rouh, T	1
Martin, S	1
Eichler, K	1
Booz, C	1
Yel, I	1
Vogl, TJ	1
Buchner, K	1
Hagenmueller, M	1
März, W	3
Frey, N	1
Hardt, SE	1
Riffel, JH	1
Georgianos, PI	5
Chedier, B	2
Roderjan, CN	2
Cavalcanti, AH	3
de Souza, F	3
Muxfeldt, ES	3
Cao, N	1
Lan, C	1
Chen, C	2
Xu, Z	1
Luo, H	1
Zheng, S	1
Gong, X	1
Ren, H	1
Li, Z	1
Qu, S	1
Yu, C	3
Yang, J	1
Jose, PA	2
Chen, Y	2
Wu, G	1
Hu, C	1
Yu, J	1
Zeng, C	1
Dragomiretskaya, NA	1
Tarzimanova, AI	1
Kucherova, JS	1
Podzolkov, VI	1
Atmanspacher, F	1
Schreckenberg, R	2
Wolf, A	1
Grgic, I	1
Schlüter, KD	2
González-Correa, C	1
Moleón, J	1
Miñano, S	1
Robles-Vera, I	1
Toral, M	1
Martín-Morales, N	1
O'Valle, F	1
Sánchez, M	1
Gómez-Guzmán, M	1
Jiménez, R	1
Romero, M	1
Duarte, J	1
Zidek, W	3
Mandal, C	1
Dutta, PK	1
Yuan, Y	1
Heizhati, M	2
Liu, Y	3
Li, N	4
Sutovska, H	1
Molcan, L	1
Majzunova, M	1
Sykora, M	1
Kopkan, L	1
Zeman, M	1
Janković, SM	1
Stojković, S	1
Petrović, M	1
Kostić, T	1
Zdravković, M	1
Radovanović, S	1
Cvjetan, R	1
Ratković, N	1
Rihor, B	1
Spiroski, D	1
Stanković, A	1
Anđelković, B	1
Gocić Petrović, R	1
Buncha, V	1
Cherezova, A	1
Alexander, S	1
Baranovskaya, I	1
Coleman, KA	1
Cherian-Shaw, M	1
Brands, MW	2
Sullivan, JC	1
O'Connor, PM	1
Mamenko, M	1
Vaios, V	1
Karligkiotis, A	1
Georgianou, E	1
Liakopoulos, V	2
Püşüroğlu, H	1
Özal, E	1
Çizgici, AY	1
Avcı, Y	1
Demir, AR	1
Bıyık, İ	1
Quencer, KB	1
Rugge, JB	1
Senashova, O	1
Funder, JW	15
Park, W	1
Whitfield, P	1
Corley, B	1
Harper, S	1
Feltham, J	1
Carroll, R	1
Moharram, M	1
Coffey, S	1
Sammut, IA	2
Wilkins, GW	1
Romero, A	2
Garza, D	2
Warren, S	3
Ma, J	2
Kucuk, N	1
Yavas Abalı, Z	1
Abalı, S	1
Canpolat, N	1
Yesil, G	1
Turan, S	1
Bereket, A	1
Guran, T	1
Ganesan, C	1
Pao, AC	1
Mikačić, I	1
Amar, J	2
Angoulvant, T	1
Boivin, JM	1
Amar, L	4
Lantelme, P	1
Blacher, J	3
Plu-Bureau, G	1
Vehier, CM	1
Kuzmin, OB	1
Buchneva, NN	1
Zhezha, VV	1
Serdyuk, SV	1
Sueta, D	1
Yamamoto, E	2
Tsujita, K	1
Kutsche, HS	1
Weber, M	1
Hirschhäuser, C	1
Rohrbach, S	1
Li, L	2
Niemann, B	1
Schulz, R	1
Gorshunova, NK	1
Savich, VV	1
Doumas, M	3
Imprialos, KP	1
Kallistratos, MS	1
Manolis, AJ	1
Cadegiani, FA	2
Yamakoshi, S	1
Ito, O	1
Rong, R	1
Ohsaki, Y	1
Nakamura, T	2
Hirose, T	1
Takahashi, K	3
Mori, T	2
Totsune, K	1
Kohzuki, M	1
Kelly, DJ	1
Kfoury, B	1
Cohen, JB	1
Ackourey, G	1
Shuey, M	1
Perkins, B	1
Nian, H	1
Luther, JM	2
Brown, N	1
Wan, N	1
Rahman, A	1
Nishiyama, A	7
Rodríguez-Sánchez, E	1
Navarro-García, JA	1
Aceves-Ripoll, J	1
González-Lafuente, L	1
Baldan-Martin, M	3
de la Cuesta, F	2
Alvarez-Llamas, G	3
Barderas, MG	3
Segura, J	3
Ruilope, LM	8
Ruiz-Hurtado, G	4
Goren, A	1
Wambier, CG	1
O'Sullivan, ED	1
MacIntyre, IM	1
Zhu, XY	1
Li, D	1
Lin, Q	1
Zhou, K	1
Cortez, AF	2
Carlos, FOC	1
Dos Santos, BDM	1
Tsujimoto, T	1
Kajio, H	1
Lin, M	2
Wang, L	2
Luo, Q	1
Li, Y	2
Yili, J	1
Hong, J	1
Yao, X	1
Zhu, Q	1
Kondratiuk, V	1
Stakhova, A	1
Hai, O	1
Karmazina, O	1
Karmazin, Y	1
Heizati, M	1
Nurula, M	1
Yang, Z	1
Wang, Z	3
Abudoyreyimu, R	1
Wu, Z	2
Tamargo, J	1
Chan, CK	2
Chang, YY	2
Tsai, YC	1
Chen, ZW	1
Wu, CY	1
Huang, WC	1
Yen, IW	1
Wu, KH	1
Wu, VC	2
Lin, YH	2
Conrad, A	1
Tataru, AP	1
Barry, AR	1
Liu, L	2
Xu, B	1
Ju, Y	1
Turgeon, R	1
Garrison, S	1
Allan, GM	1
Siddiqui, M	1
Judd, EK	1
Oparil, S	11
Calhoun, DA	16
Stanton, T	1
Reid, CM	1
Keech, A	1
Roberts-Thomson, P	1
Stewart, S	1
Greenough, R	1
Stowasser, M	4
Abhayaratna, WP	1
Kawasaki, M	1
Yamada, T	2
Okuyama, Y	1
Morita, T	1
Furukawa, Y	1
Tamaki, S	1
Iwasaki, Y	1
Kikuchi, A	1
Sakata, Y	1
Fukunami, M	1
Sawai, T	1
Dohi, K	1
Fujimoto, N	1
Okubo, S	1
Isaka, N	1
Ichikawa, T	1
Makino, K	1
Okamoto, S	1
Koyabu, S	1
Kitamura, T	1
Ogura, T	1
Tamaru, S	1
Nishikawa, M	1
Nakamura, M	1
Ito, M	2
Martin-Lorenzo, M	2
Martinez, PJ	2
Prado, JC	1
Vivanco, F	2
Yugar-Toledo, JC	2
Modolo, R	2
de Faria, AP	2
Moreno, H	4
Yan, Y	1
Wang, C	3
Lu, Y	1
Gong, H	1
Ma, X	1
Li, H	1
Wang, B	1
Zhang, X	2
Claggett, BL	1
Liu, J	1
Vardeny, O	1
Pitt, B	6
Zannad, F	9
Solomon, S	1
Good, ME	1
Chiu, YH	1
Poon, IKH	1
Medina, CB	1
Butcher, JT	1
Mendu, SK	1
DeLalio, LJ	1
Lohman, AW	1
Leitinger, N	1
Barrett, E	1
Lorenz, UM	1
Desai, BN	1
Jaffe, IZ	1
Bayliss, DA	1
Isakson, BE	1
Ravichandran, KS	1
Kiuchi, MG	1
Chen, S	1
Hoye, NA	1
Pürerfellner, H	1
DeCarlo, KE	1
Agrawal, N	1
Morganti, A	1
Mancia, G	2
Oliveras, A	4
Armario, P	4
Sans, L	2
Clarà, A	2
Vázquez, S	3
Molina, L	1
Pareja, J	2
de la Sierra, A	4
Pascual, J	3
Brandani, L	1
Duprez, D	2
Toleuova, A	1
Krieger, EM	2
Drager, LF	2
Giorgi, DMA	1
Pereira, AC	2
Barreto-Filho, JAS	1
Nogueira, AR	1
Mill, JG	4
Lotufo, PA	1
Amodeo, C	1
Batista, MC	2
Bodanese, LC	1
Carvalho, ACC	1
Castro, I	1
Chaves, H	1
Costa, EAS	1
Feitosa, GS	1
Franco, RJS	1
Fuchs, FD	1
Guimarães, AC	1
Jardim, PC	1
Machado, CA	1
Magalhães, ME	1
Mion, D	1
Nascimento, RM	1
Nobre, F	1
Nóbrega, AC	1
Ribeiro, ALP	1
Rodrigues-Sobrinho, CR	1
Sanjuliani, AF	1
Teixeira, MDCB	1
Krieger, JE	2
Sandesara, PB	1
O'Neal, WT	1
Kelli, HM	1
Topel, M	1
Samman-Tahhan, A	1
Sperling, LS	1
Bursztyn, M	1
Touyz, RM	5
Laffer, CL	1
Carey, RM	6
Dominiczak, AF	1
MacDonald, TM	10
Morant, SV	2
Webb, DJ	3
Sever, P	3
McInnes, GT	4
Ford, I	5
Cruickshank, JK	5
Caulfield, MJ	2
Padmanabhan, S	2
Mackenzie, IS	2
Salsbury, J	3
Brown, MJ	6

Trial	Phase	Enrollment	Study Type	Start Date	Status
A Randomized, Double-Blind, Placebo Controlled, Parallel Group Study of Patiromer for the Enablement of Spironolactone Use for Blood Pressure Control in Patients With Resistant Hypertension and Chronic Kidney Disease[NCT03071263]	Phase 2	295 participants (Actual)	Interventional	2017-01-23	Completed
Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist (TOPCAT)[NCT00094302]	Phase 3	3,445 participants (Actual)	Interventional	2006-08-31	Completed
Sympathetic Renal Denervation Versus Increment of Pharmacological Treatment in Resistant Arterial Hypertension[NCT02039492]		38 participants (Actual)	Interventional	2012-09-30	Completed
Multicenter Study of Patients With Hypertension Resistant to Patient Identification and Standardization of Therapeutic[NCT01643434]	Phase 4	2,000 participants (Anticipated)	Interventional	2012-08-31	Recruiting
Optimum Treatment for Drug-Resistant Hypertension[NCT02369081]	Phase 4	348 participants (Actual)	Interventional	2009-05-31	Active, not recruiting
Southern Danish Hypertension and Diabetes Study (SDHDS) With Amiloride[NCT02122731]	Phase 4	80 participants (Actual)	Interventional	2010-11-30	Completed
Mineralocorticoid Receptor and Obesity Induced Cardiovascular Complications[NCT01406015]		38 participants (Actual)	Interventional	2009-02-28	Completed
Aldosterone and Glucose Homeostasis[NCT00732160]		34 participants (Actual)	Interventional	2008-09-30	Completed
Caveolin-1 and Vascular Dysfunction[NCT01426529]	Phase 1	120 participants (Anticipated)	Interventional	2010-10-01	Active, not recruiting
Salt Sensitive Hypertension and Striatin[NCT03683069]	Phase 4	400 participants (Actual)	Interventional	2019-01-15	Active, not recruiting
South Danish Hypertension and Diabetes Study[NCT01062763]	Phase 3	119 participants (Actual)	Interventional	2010-03-31	Completed
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
Effect of Mineralcorticoid Recept Antagonist on Cardiovascular Disease in Patients With Hypertension and Hyperaldosteronemia：A Multicenter Randomized Controlled Study[NCT05688579]	Phase 4	8,000 participants (Anticipated)	Interventional	2023-04-16	Enrolling by invitation
Addition of Spironolactone in Patients With Resistant Arterial Hypertension[NCT00524615]	Phase 4	160 participants (Anticipated)	Interventional	2007-09-30	Recruiting
HYpertension Therapy With Valsartan Versus EpleRenone for Obese Patients: A Randomized Clinical Trial[NCT03476616]	Phase 4	330 participants (Anticipated)	Interventional	2018-09-01	Not yet recruiting
Prevalence and Treatment of Resistant Hypertension in Diabetic Patients in Yaounde[NCT02426099]	Phase 4	17 participants (Actual)	Interventional	2011-10-31	Completed
68Ga-Pentixafor PET/CT for the Subtyping Diagnosis of Primary Aldosteronism: A Prospective Diagnostic Accuracy Study[NCT05131061]		100 participants (Actual)	Observational	2021-11-11	Completed
Efficacy of Continuous Positive Airway Pressure (CPAP) on Blood Pressure Control of Resistant Hypertension Patients With Obstructive Sleep Apnea Syndrome (OSAS).[NCT01508754]	Phase 4	125 participants (Actual)	Interventional	2012-01-31	Completed
Effects of Mineralocorticoid and AT-1 Receptor Antagonism on the Aldosterone-Renin Ratio (ARR) In Primary Aldosteronism Patients (EMIRA Study): Rationale and Design[NCT04185857]		50 participants (Actual)	Observational	2018-01-01	Completed
Prospective Cross-sectional Study on Prevalence of Primary Aldosteronism in Resistant Hypertension and Association With Cardiometabolic Complications[NCT04213963]		100 participants (Anticipated)	Observational	2011-09-01	Recruiting
The Intra-Procedural Cortisol Assay During Adrenal Vein Sampling: Rationale andDesign of A Randomized Study (I-PADUA)[NCT03449797]		200 participants (Anticipated)	Interventional	2018-04-01	Not yet recruiting
Effects of Eplerenone on Left Ventricular Hypertrophy in Patients With Resistant Hypertension and Obstructive Sleep Apnoea[NCT03186742]	Phase 4	125 participants (Actual)	Interventional	2014-07-01	Completed
Randomized Controlled Trial of Spironolactone Versus Standard of Care Blood Pressure Treatment on the Severity of Obstructive Sleep Apnea in Patients With Resistant Hypertension[NCT01897727]		41 participants (Actual)	Interventional	2009-01-31	Completed
Resistant Hypertension On Treatment - Sequential Nephron Blockade Compared to Dual Blockade of the Renin-angiotensin-aldosterone System Plus Bisoprolol in the Treatment of Resistant Arterial Hypertension: A Randomized Trial (ResHypOT)[NCT02832973]	Phase 4	72 participants (Actual)	Interventional	2015-09-30	Completed
The Effect of Spironolactone and Vitamin E Versus Vitamin E on Serum Adipocytokines Levels in Patients With Biopsy-proven Nonalcoholic Fatty Liver Disease-A Phase II Study[NCT01147523]	Phase 2	30 participants (Actual)	Interventional	2010-01-31	Completed
Neural Mechanisms of Thiazide-induced Insulin Resistance[NCT00353652]	Phase 4	166 participants (Actual)	Interventional	2005-01-31	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
Eplerenone for Central Serous Chorioretinopathy: A Pilot Study[NCT01822561]	Phase 2	17 participants (Actual)	Interventional	2013-05-31	Completed
The Prevalence and the Prognosis of Resistant Hypertension Ascertained With Systemic Investigation and Optimal Treatment With Antihypertensive Drugs[NCT01703780]		9,638 participants (Actual)	Observational	2012-07-31	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
Increasing Stay-on-therapy in Hypertensive Patients Treated With First-line Diuretics: An Active Pharmacosurveillance and Pharmacogenetic Study.[NCT00408512]	Phase 4	2,500 participants (Anticipated)	Interventional	2006-12-31	Completed
Randomized Trial of Spironolactone Versus Amiloride as an Add on Agent in Resistant Hypertension[NCT00709137]		0 participants (Actual)	Interventional	2008-10-31	Withdrawn (stopped due to lack of enrollment)
Aldosterone-Renin Ratio to Diagnose Primary Aldosteronism in a Population of Patients With Therapy-Resistant Hypertension: Test Characteristics, Diagnostic Value and Predictive Value for Antihypertensive Treatment. The Dutch ARRAT Study.[NCT00407784]		500 participants	Observational	2007-01-31	Recruiting
Characteristics Predicting Clinically Relevant Reduction of Hypertension Following Adrenalectomy for Primary Aldosteronism: a Multicenter Analysis[NCT04761354]		514 participants (Actual)	Observational	2016-03-26	Completed
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)
Increased Activity of the Epithelial Sodium Channel (ENaC) in Diabetic Nephropathy[NCT01918488]		80 participants (Anticipated)	Interventional	2013-10-31	Enrolling by invitation
Randomized Double-Blind Placebo-Controlled Study of Pyrazinoylguanidine Hydrochloride (Amiloride) in Subjects With Coronary Artery Disease[NCT01228214]	Phase 2/Phase 3	100 participants (Actual)	Interventional	2011-03-31	Active, not recruiting
A Double-Blind, Parallel Design Study to Compare the Effectiveness of Eplerenone Versus Atenolol in Reversing the Remodeling of Resistance Arteries in Subjects With Mild to Moderate Primary Hypertension[NCT00147563]	Phase 4	34 participants	Interventional	2003-10-31	Completed
A Double-Blind, Randomized, Parallel Design Study of Aliskiren Versus Hydrochlorothiazide in Mild-to Moderate Hypertensive Type II Diabetes Mellitus Patients on Remodeling of Resistance Arteries[NCT01480791]	Phase 2	0 participants (Actual)	Interventional	2012-01-31	Withdrawn (stopped due to Because of results of Altitude trial, this trial was cancelled.)
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

AOBP: Automated Office Blood Pressure SBP: Systolic Blood Pressure BP: Blood Pressure (NCT03071263)
Timeframe: From baseline to Week 12

Change in AOBP SBP From Baseline to Week 12 Regardless of Increase in Antihypertensives

Intervention	mmHg (Mean)
Group 1 - Patiromer	-11.3
Group 2 - Placebo	-11.0

AOBP SBP: Automated Office Systolic Blood Pressure (NCT03071263)
Timeframe: From baseline to Week 12

Number of Participants Remaining on Spironolactone at Week 12

Intervention	mmHg (Mean)
Group 1 - Patiromer	-11.3
Group 2 - Placebo	-11.2

The proportion of subjects remaining on spironolactone at Week 12 will be compared between treatment groups (spironolactone/patiromer versus spironolactone/placebo). Subjects who discontinued from the study early or discontinued study spironolactone prior to Week 12, for any reason, were considered as not having remained on spironolactone until Week 12. (NCT03071263)
Timeframe: At week 12

Central Serum Potassium Change From Baseline to Week 12 by Baseline Serum Potassium Category

Intervention	Participants (Count of Participants)
Group 1 - Patiromer	126
Group 2 - Placebo	98

"The two baseline potassium subgroups, 4.3-<4.7 mEq/L versus 4.7-5.1 mEq/L, are based on central laboratory data.~If a participant's serum potassium result at baseline was not in one of the two subgroups reported below, the participant's potassium stratum at randomization was used. Therefore, participants with BCSP <4.3 mEq/L or >5.1 mEq/L at baseline (Day 0) have been classified according to their serum potassium values at the Screening period." (NCT03071263)
Timeframe: From baseline to Week 12

Number of Participants by Spironolactone Dose Prescribed at Each Visit

Intervention	mEq/L (Mean)
	Baseline Central Serum Potassium 4.3-<4.7 mEq/L	Baseline Central Serum Potassium 4.7-<5.1 mEq/L	Overall
Group 1 - Patiromer	0.16	-0.09	0.02
Group 2 - Placebo	0.40	0.03	0.20

"QD: Once daily~QOD: Once every other day" (NCT03071263)
Timeframe: From baseline to Week 10

Number of Participants Requiring Additional New Antihypertensive Medications or Increases to Baseline Antihypertensive Medications

Intervention	Participants (Count of Participants)
	50 mg QD : Baseline	50 mg QD : Week 1	50 mg QD : Week 2	50 mg QD : Week 3	50 mg QD : Week 4	50 mg QD : Week 6	50 mg QD : Week 8	50 mg QD : Week 10	25 mg QD : Baseline	25 mg QD : Week 1	25 mg QD : Week 2	25 mg QD : Week 3	25 mg QD : Week 4	25 mg QD : Week 6	25 mg QD : Week 8	25 mg QD : Week 10	25 mg QOD : Baseline	25 mg QOD : Week 1	25 mg QOD : Week 2	25 mg QOD : Week 3	25 mg QOD : Week 4	25 mg QOD : Week 6	25 mg QOD : Week 8	25 mg QOD : Week 10
Group 1 - Patiromer	0	0	0	86	105	106	106	106	147	145	140	49	27	25	26	19	0	1	3	3	3	2	1	2
Group 2 - Placebo	0	0	0	76	94	96	85	80	148	144	142	57	34	28	24	20	0	2	1	2	3	2	4	4

"Row Titles:~AM: Antihypertensive Medication(s)~New AM: Participants who required additional new antihypertensive medication(s)~Increases to baseline AM: Participants who required increases to baseline antihypertensive medication(s)~Addition new (or increase) AM: Participants who required addition of new antihypertensive medication(s) and/or increases to baseline antihypertensive medications~At any time during the study: During study~While on study medication: On medication" (NCT03071263)
Timeframe: From baseline to Week 12/Early Termination visit

Participants Having Spironolactone Titrations Over Time

Intervention	participants (Number)
	New AM : At any time during the study	New AM : On medication	Increases to baseline AM: During study	Increases to baseline AM: On medication	Addition new (or increases) AM: During study	Addition new (or increases) AM : On medication
Group 1 - Patiromer	0	0	0	0	0	0
Group 2 - Placebo	3	1	2	1	4	2

"The titration was performed according to the following criteria: Spironolactone was increased in cases of hypertension, decreased or stopped in cases of hypotension and maintained if the blood pressure results were adequate~The symbols > and ≤ included in the row titles are used to indicate the time interval [>Week1 and ≤Week2 meaning from day 8 until day 14 (included)]." (NCT03071263)
Timeframe: From baseline to Week 12

Participants With Central Serum Potassium <5.5 mEq/L Over Time

Intervention	Participants (Count of Participants)
	Up : ≤Week 1	Up : >Week 1 and ≤Week 2	Up : >Week 2 and ≤Week 3	Up : >Week 3 and ≤Week 4	Up : >Week 4 and ≤Week 6	Up : >Week 6 and ≤Week 8	Up : >Week 8 and ≤Week 10	Up : >Week 10 and ≤Week 12	Down : ≤Week 1	Down : >Week 1 and ≤Week 2	Down : >Week 2 and ≤Week 3	Down : >Week 3 and ≤Week 4	Down : >Week 4 and ≤Week 6	Down : >Week 6 and ≤Week 8	Down : >Week 8 and ≤Week 10	Down : >Week 10 and ≤Week 12
Group 1 - Patiromer	0	0	88	27	10	6	6	1	1	2	2	6	8	5	4	3
Group 2 - Placebo	0	0	77	21	11	6	7	0	2	0	2	5	7	8	7	1

"Baseline Central Serum Potassium: BCSP.~The symbols > and ≤ included in the row titles are used to indicate the time interval [>Week1 and ≤Week2 meaning from day 8 until day 14 (included)].~If a participant's serum potassium result at baseline was not in one of the two subgroups reported below, the participant's potassium stratum at randomization was used. Therefore, participants with BCSP <4.3 mEq/L or >5.1 mEq/L at baseline (Day 0) have been classified according to their serum potassium values at the Screening period." (NCT03071263)
Timeframe: From baseline to Week 12

Shifts in Selected Laboratory Tests From Baseline to End of Treatment

Intervention	Participants (Count of Participants)
	BCSP 4.3-<4.7mEq/L: ≤Week1	BCSP 4.3-<4.7mEq/L: >Week1 and ≤Week2	BCSP 4.3-<4.7mEq/L: >Week 2 and ≤Week 3	BCSP 4.3-<4.7mEq/L: >Week 3 and ≤Week 4	BCSP 4.3-<4.7mEq/L: >Week 4 and ≤Week 6	BCSP 4.3-<4.7mEq/L: >Week 6 and ≤Week 8	BCSP 4.3-<4.7mEq/L: >Week 8 and ≤Week 10	BCSP 4.3-<4.7mEq/L: > Week 10 and ≤ Week 12	BCSP 4.7-<5.1 mEq/L: ≤Week 1	BCSP 4.7-<5.1mEq/L: >Week 1 and ≤Week 2	BCSP 4.7-<5.1mEq/L: >Week 2 and ≤Week 3	BCSP 4.7-<5.1mEq/L: >Week 3 and ≤Week 4	BCSP 4.7-<5.1 mEq/L: >Week 4 and ≤Week 6	BCSP 4.7-<5.1mEq/L: >Week 6 and ≤Week 8	BCSP 4.7-<5.1mEq/L: >Week 8 and ≤Week 10	BCSP 4.7-<5.1mEq/L: >Week 10 and ≤Week 12	Overall : ≤Week 1	Overall : > Week 1 and ≤Week 2	Overall : >Week 2 and ≤Week 3	Overall : >Week 3 and ≤Week 4	Overall : >Week 4 and ≤Week 6	Overall : >Week 6 and ≤Week 8	Overall : >Week 8 and ≤Week 10	Overall : >Week 10 and ≤Week 12
Group 1 - Patiromer	60	57	59	61	61	61	58	61	75	74	74	74	79	74	72	80	135	131	133	135	140	135	130	141
Group 2 - Placebo	62	57	63	60	61	58	58	61	66	65	65	61	64	66	66	65	128	122	128	121	125	124	124	126

"The end of treatment value is defined as the last non-missing value on or prior to the last spironolactone dose date (from End of Treatment - Case report form) + 3 days~LLN=Lower limit of the normal range. ULN=Upper limit of the normal range. EoT=End of Treatment" (NCT03071263)
Timeframe: From Baseline to End of Treatment, up to 12 weeks.

Spironolactone Dose Level at End of 12 Weeks of Study Treatment

Intervention	participants (Number)
	Magnesium - Baseline Value	Magnesium - Baseline Value	Magnesium - Baseline Value ULN	Magnesium - Baseline Value Normal : EoT Value	Magnesium- Baseline Value Normal: EoT Value Normal	Magnesium - Baseline Value Normal : EoT Value >ULN	Magnesium - Baseline Value >ULN : EoT Value	Magnesium - Baseline Value >ULN : EoT Value Normal	Magnesium - Baseline Value >ULN : EoT Value >ULN	Phosphate - Baseline Value	Phosphate - Baseline Value	Phosphate - Baseline Value ULN	Phosphate - Baseline Value Normal : EoT Value	Phosphate- Baseline Value Normal: EoT Value Normal	Phosphate - Baseline Value Normal : EoT Value >ULN	Phosphate - Baseline Value >ULN : EoT Value	Phosphate - Baseline Value >ULN : EoT Value Normal	Phosphate - Baseline Value >ULN : EoT Value >ULN	Calcium - Baseline Value	Calcium - Baseline Value	Calcium - Baseline Value ULN	Calcium - Baseline Value Normal : EoT Value	Calcium - Baseline Value Normal : EoT Value Normal	Calcium - Baseline Value Normal : EoT Value >ULN	Calcium - Baseline Value >ULN : EoT Value	Calcium - Baseline Value >ULN : EoT Value Normal	Calcium - Baseline Value >ULN : EoT Value >ULN
Group 1 - Patiromer	9	3	0	12	103	6	0	10	3	0	1	0	0	136	2	0	5	2	2	5	0	4	133	0	0	2	0
Group 2 - Placebo	4	8	0	7	109	10	0	6	3	1	3	0	1	125	8	0	4	5	4	1	0	6	133	0	0	1	2

"Row title:~Participants not completing 12W of study treatment: Participants who had not completed 12 weeks of study treatment." (NCT03071263)
Timeframe: 12 Weeks of Study Treatment

Aborted Cardiac Arrest

Intervention	Participants (Count of Participants)
	50 mg QD	25 mg QD	25 mg QOD	Participants not completing 12W of study treatment
Group 1 - Patiromer	102	22	2	21
Group 2 - Placebo	76	19	3	50

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.

Change From Baseline in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR)

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

Insulin resistance was measured using the 75 G glucose tolerance test. Participants ingested 75 grams of glucose in 300-400 mL of water over 5 minutes. Blood samples were taken before ingesting glucose and then every 30 minutes for 120 minutes. HOMA-IR was calculated using the Insulin and glucose levels obtained. A negative change (decrease in insulin resistance) indicates improvement. (NCT01406015)
Timeframe: Baseline and Week 6 (Prior to ingesting glucose and every 30 minutes for 120 minutes)

Change From Baseline in Insulin Sensitivity Index (ISI)

Intervention	IR index (Mean)
	Baseline	Change from Baseline at Week 6
Placebo	3.4	0.1
Spironolactone	2.7	0.1

Insulin sensitivity was measured using the 75 gram (G) glucose tolerance test. Participants ingested 75 grams of glucose in 300-400 milliliters (mL) of water over 5 minutes. Blood samples were taken before ingesting glucose and then every 30 minutes for 120 minutes. Insulin sensitivity index was calculated by Matsuda and Defronzo's formula using the values obtained. A positive change from Baseline (increase in insulin sensitivity) indicates improvement. (NCT01406015)
Timeframe: Baseline and Week 6 (Prior to ingesting glucose and every 30 minutes for 120 minutes)

Change From Baseline in Para-aminohippurate (PAH) Clearance

Intervention	IS index (Mean)
	Baseline	Change from Baseline at Week 6
Placebo	4.6	-1.1
Spironolactone	3.7	-0.1

Renal plasma blood flow was determined by clearance of para-aminohippurate (PAH). A loading dose of PAH (8 mg/kg) was given intravenously followed by a 1 hour constant infusion of PAH at a rate of 12 mg/minute (min). Plasma samples were obtained at Baseline and at 50 and 60 minutes. PAH clearance was calculated from the plasma levels and infusion rates and reported in millimeters (mL)/minute (min). A positive change from Baseline indicates improvement. (NCT01406015)
Timeframe: Baseline and Week 6 (Prior to PAH infusion and at 50 and 60 minutes post PAH infusion)

Change From Baseline in Post-ischemic Dilatation

Intervention	mL/min (Mean)
	Baseline	Change from Baseline at Week 6
Placebo	521	-5.2
Spironolactone	488	-2.3

Ultrasonography of the brachial artery was performed to evaluate endothelial function by flow mediated dilatation (FMD) studies. A blood pressure cuff was placed on the participant's upper arm and was compressed for 5 minutes. After release of compression, brachial artery diameter and blood flow velocity were measured. FMD was expressed as the percentage change in brachial artery diameter. A positive change from Baseline indicates improvement. (NCT01406015)
Timeframe: Baseline and Week 6

Insulin Secretion

Intervention	percent dilalation (Mean)
	Baseline	Change from Baseline at Week 6
Placebo	10.2	-2.0
Spironolactone	9.6	-1.2

Acute Insulin response during Hyperglycemic clamp (delta insulin uU/mL, t=0-10) (NCT00732160)
Timeframe: 3 hours

Insulin Sensitivity

Intervention	uU/mL (Mean)
Vehicle, HS	48.9
Vehicle, LS	37.6
Aldosterone, HS	51.8
Aldosterone, LS	34.4

Insulin sensitivity index (ISI) was calculated by dividing the average glucose infusion rate (mg glucose infusion/kg body weight/min) by the average insulin concentration (uU/mL) from 90 to 120 minutes. This was multiplied by 100 (thus, x100 in units description), per reporting convention in literature. (NCT00732160)
Timeframe: 3 hours

Adverse Effects

Change of Diastolic Blood Pressure

Intervention	mg/kg/min per uU/mL*100 (Mean)
Vehicle, HS	25.2
Vehicle, LS	24.8
Aldosterone, HS	23.4
Aldosterone, LS	24.7

Intervention	participants (Number)
Addition of Spironolactone	4
Placebo	0

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

Change of of Systolic Blood Pressure

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

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

Severity of Obstructive Sleep Apnea

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

3 month change in apnea-hypopnea index assessed by diagnostic, full-night polysomnography. AHI values are typically categorized as 5-15/hr = mild; 15-30/hr = moderate; and > 30/h = severe. (NCT01897727)
Timeframe: baseline and 3 months

24-hour Ambulatory Systolic Blood Pressure

HOMA-IR

Intervention	events/hour (Mean)
Spironolactone	-18.3
Standard of Care BP Treatment	7.0

Intervention	mmHg (Mean)
Study#1: Chlorthalidone (CTD), Titrated Dose	127.4
Study #1: Spironolactone (SP), Titrated Dose	128.6
Study# 2 Chlorthalidone (CTD), Fixed Dose	123.5
Study# 2 CTD Fixed Dose 25 mg/d Plus SP Fixed Dose	121.6
Study# 2 CTD Fixed Dose 25 mg/d Plus IR Fixed Dose	119.8

assessment of insulin resistance calculated by multiplying fasting plasma insulin (mU/l) with fasting plasma glucose (mmol/l) divided by 22.5. (NCT00353652)
Timeframe: 3 months

Insulin

Sympathetic Baroreflex Sensitivity

slope relating percent change in SNA (% change in total activity from baseline) to diastolic BP. (NCT00353652)
Timeframe: 3 months

Sympathetic Nerve Activity

Change in Best Corrected Visual Acuity

Visual acuity will be measured with standard eye charts, with manifest refraction at the initiation and conclusion of treatment. Although an important measure, this was not chosen as the primary outcome measure, as some patients with central serous chorioretinopathy may have a normal visual acuity when properly refracted (refraction can change with elevation of the macula by sub-retinal fluid) (NCT01822561)
Timeframe: Baseline and 1 month after treatment

Change in Macular Thickness

Automated software to calculate the thickness of the macula is standard on commercial OCT devices. Macular thickness before and after treatment will be assessed and compared. (NCT01822561)
Timeframe: Baseline and 1 month after treatment

Change in Serum Potassium

Eplerenone can cause elevation of serum potassium. After initial screening, serum potassium was evaluated at 1 and 4 weeks after baseline. (NCT01822561)
Timeframe: Baseline and 1 month after treatment

Change in Subfoveal Choroidal Thickness, Study Eye

Choroidal thickness can be measured using optical coherence tomography, and is known to be affected in patients with central serous chorioretinopathy. Thickness of the choroid under the fovea will be manually calculated in both the study eye. (NCT01822561)
Timeframe: Baseline and 1 month after treatment

Complete Resolution of Subretinal Fluid

Optical coherence tomography is an imaging technique capable of extremely high resolution (~5-7 microns) imaging of the macula, and is able to detect the presence and amount of subretinal fluid present, the key anatomic abnormality in Central Serous Chorioretinopathy (NCT01822561)
Timeframe: Baseline and 1 month after treatment

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

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)

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)

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)

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

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

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')

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).

Intervention	mU/liter (Median)
Study#1: Chlorthalidone (CTD), Titrated Dose	8.24
Study #1: Spironolactone (SP), Titrated Dose	7.6
Study# 2 CTD Fixed Dose 25 mg/d	7.6
Study# 2 CTD Fixed Dose 25 mg/d Plus SP Fixed Dose	4.87
Study# 2 CTD Fixed Dose 25 mg/d Plus IR Fixed Dose	6.8

Intervention	% change from baseline per mmHg (Mean)
Study#1: Chlorthalidone (CTD), Titrated Dose	-9.1
Drug: Study #1: Spironolactone (SP), Titrated Dose	-15.2
Study# 2 Chlorthalidone (CTD), Fixed Dose	-12.9
Study# 2 CTD Fixed Dose 25 mg/d Plus SP Fixed Dose	-11.3
Study# 2 CTD Fixed Dose 25 mg/d Plus IR Fixed Dose	-12.0

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

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

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

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

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

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

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

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

spironolactone and Hypertension

Research Excerpts

Research

Studies (1,181)

Authors

Clinical Trials (41)

Trial Overview

Trial Outcomes

Change in AOBP SBP From Baseline to Week 12 or Last Available AOBP SBP Prior to Addition of Any New BP Medications or Increase From Any Baseline BP Medications

Change in AOBP SBP From Baseline to Week 12 Regardless of Increase in Antihypertensives

Number of Participants Remaining on Spironolactone at Week 12

Central Serum Potassium Change From Baseline to Week 12 by Baseline Serum Potassium Category

Number of Participants by Spironolactone Dose Prescribed at Each Visit

Number of Participants Requiring Additional New Antihypertensive Medications or Increases to Baseline Antihypertensive Medications

Participants Having Spironolactone Titrations Over Time

Participants With Central Serum Potassium <5.5 mEq/L Over Time

Shifts in Selected Laboratory Tests From Baseline to End of Treatment

Spironolactone Dose Level at End of 12 Weeks of Study Treatment

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

Change From Baseline in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR)

Change From Baseline in Insulin Sensitivity Index (ISI)

Change From Baseline in Para-aminohippurate (PAH) Clearance

Change From Baseline in Post-ischemic Dilatation

Insulin Secretion

Insulin Sensitivity

Adverse Effects

Change of Diastolic Blood Pressure

Change of of Systolic Blood Pressure

Severity of Obstructive Sleep Apnea

24-hour Ambulatory Systolic Blood Pressure

HOMA-IR

Insulin

Sympathetic Baroreflex Sensitivity

Sympathetic Nerve Activity

Change in Best Corrected Visual Acuity

Change in Macular Thickness

Change in Serum Potassium

Change in Subfoveal Choroidal Thickness, Study Eye

Complete Resolution of Subretinal Fluid

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