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1.
Medicine (Baltimore) ; 100(5): e23188, 2021 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-33592818

RESUMO

ABSTRACT: To explore the short-term effect of high-dose spironolactone (80 mg/d) on chronic congestive heart failure (CHF).The general clinical data of 211 patients with CHF from February 2016 to August 2019 were collected and analyzed. Patients were divided into Low-dose group (taking 40 mg/d spironolactone) and High-dose group (taking 80 mg/d spironolactone) according to the patient's previous dose of spironolactone. The changes of B-type brain natriuretic peptide (BNP), NT-pro BNP (N terminal pro B type natriuretic peptide), echocardiography, 6-minute walking test (6MWT), and comprehensive cardiac function assessment data were collected for analysis.Compared with before treatment, the blood potassium of the two groups increased significantly (P < .05), but the blood potassium did not exceed the normal range. Compared with before treatment, BNP, NT-pro BNP, LVEDD, LVEDV and NYHA grading were significantly decreased (P < .05), LVEF and 6-MWT were significantly increased (P < .05). Compared with the Low-dose group, the high-dose group BNP (117.49 ±â€Š50.32 vs 195.76 ±â€Š64.62, P < .05), NT-pro BNP (312.47 ±â€Š86.28 vs 578.47 ±â€Š76.73, P < .05), LVEDD (45.57 ±â€Š5.69 vs 51.96 ±â€Š5.41, P <.05), LVEDV (141.63 ±â€Š51.14 vs 189.85 ±â€Š62.49, P < .05) and NYHA grading (1.29 ±â€Š0.41 vs 1.57 ±â€Š0.49, P < .05) were significantly reduced, but, 6-MWT (386.57 ±â€Š69.72 vs 341.73 ±â€Š78.62, P < .05), LVEF (41.62 ±â€Š2.76 vs 36.02 ±â€Š2.18, P < .05) and total effective rate (92.68% vs 81.39%, P < .05) increased significantly.Compared with 40 mg spironolactone, 80 mg spironolactone can rapidly reduce BNP and NT-pro BNP concentration, enhance exercise tolerance, improve clinical signs and cardiac function classification, and has better efficacy.


Assuntos
Insuficiência Cardíaca/tratamento farmacológico , Espironolactona/uso terapêutico , Idoso , Relação Dose-Resposta a Droga , Ecocardiografia , Feminino , Testes de Função Cardíaca , Humanos , Masculino , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Potássio/sangue , Estudos Retrospectivos , Espironolactona/administração & dosagem , Teste de Caminhada
2.
Med. clín (Ed. impr.) ; 155(7): 302-308, oct. 2020. tab
Artigo em Espanhol | IBECS | ID: ibc-195877

RESUMO

El hiperaldosteronismo primario (HAP) se asocia con una mayor morbimortalidad cardiovascular y renal que la hipertensión arterial (HTA) esencial, a misma edad, sexo y grado de HTA. Por ello, es esencial instaurar un tratamiento específico para aminorar los efectos deletéreos del exceso de aldosterona. Aunque se considera que la adrenalectomía es generalmente el tratamiento de elección en los casos de HAP por enfermedad unilateral, se deben tener en cuenta varios aspectos y circunstancias que pueden hacer más adecuado el tratamiento médico. Entre ellos, en esta revisión se mencionan, la limitada experiencia y eficacia, y los riesgos del cateterismo de venas adrenales; los riesgos y baja eficacia de la adrenalectomía; la elevada seguridad y eficacia del tratamiento médico y algunas situaciones especiales como el embarazo, la edad avanzada o las formas familiares, en las que el tratamiento médico se considera especialmente indicado como primera línea. También se comentan los principales estudios que comparan el tratamiento médico y quirúrgico en el HAP


Primary aldosteronism is associated with higher cardiovascular and renal morbidity and mortality than essential hypertension in age- and sex-matched patients with the same degree of blood pressure elevation. Therefore, it is essential to establish a specific treatment to avoid the deleterious effects of aldosterone excess. Although adrenalectomy is generally considered the treatment of choice in cases of primary aldosteronism due to unilateral disease, several aspects and circumstances should be taken into account that may make medical treatment more appropriate. Among them, in this review we mention the limited experience and efficacy, and the potential risks of adrenal vein sampling; the risks and low efficacy of adrenalectomy; the high safety and efficacy of medical treatment and some special situations such as primary aldosteronism during pregnancy, in patients of advanced age or hereditary forms of primary aldosteronism, in which medical treatment is considered especially indicated as the first line therapy. The main studies comparing medical and surgical treatment in primary aldosteronism are also discussed


Assuntos
Humanos , Idoso , Idoso de 80 Anos ou mais , Hiperaldosteronismo/terapia , Adrenalectomia/métodos , Gerenciamento Clínico , Cateterismo/métodos , Eplerenona/administração & dosagem , Espironolactona/administração & dosagem , Sensibilidade e Especificidade , Glucocorticoides/administração & dosagem
3.
Am J Cardiol ; 129: 36-41, 2020 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-32565090

RESUMO

Electrolyte abnormalities are a known trigger for ventricular arrhythmia, and patients with heart disease on diuretic therapy may be at higher risk for electrolyte depletion. Our aim was to determine the prevalence of electrolyte depletion in patients presenting to the hospital with sustained ventricular tachycardia or ventricular fibrillation (VT/VF) versus heart failure, and identify risk factors for electrolyte depletion. Consecutive admissions to a tertiary care hospital for VT/VF were identified between July 2016 and October 2018 using the electronic medical record and compared with an equal number of consecutive admissions for heart failure (CHF). The study included 280 patients (140 patients in each group; mean age 63, 60% male, 59% African American). Average EF in the VT/VF and CHF groups was 30% and 33%, respectively. Hypokalemia (K < 3.5 mmol/L) and severe hypokalemia (K < 3.0 mmol/L) were present in 35.7% and 13.6%, respectively, of patients with VT/VF, compared to 12.9% and 2.7% of patients with CHF (p < 0.001 and p = 0.001, respectively, between groups). Hypomagnesemia was found in 7.8% and 5.8% of VT/VF and CHF patients, respectively (p = 0.46). Gastrointestinal illness and recent increases in diuretic dose were strongly associated with severe hypokalemia in VT/VF patients (odds ratio: 11.1 and 21.9, respectively; p < 0.001). In conclusion, hypokalemia is extremely common in patients presenting with VT/VF, much more so than in patients with CHF alone. Preceding gastrointestinal illness and increase in diuretic dose were strongly associated with severe hypokalemia in the VT/VF population, revealing a potential opportunity for early intervention and arrhythmia risk reduction.


Assuntos
Diuréticos/administração & dosagem , Insuficiência Cardíaca/epidemiologia , Hipopotassemia/epidemiologia , Magnésio/sangue , Taquicardia Ventricular/epidemiologia , Fibrilação Ventricular/epidemiologia , Idoso , Cardiomiopatias/epidemiologia , Estudos de Casos e Controles , Diarreia/epidemiologia , Feminino , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/tratamento farmacológico , Humanos , Hipopotassemia/sangue , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/epidemiologia , Náusea/epidemiologia , Insuficiência Renal Crônica/epidemiologia , Índice de Gravidade de Doença , Inibidores de Simportadores de Cloreto de Sódio/administração & dosagem , Inibidores de Simportadores de Cloreto de Sódio e Potássio/administração & dosagem , Espironolactona/administração & dosagem , Volume Sistólico , Taquicardia Ventricular/sangue , Fibrilação Ventricular/sangue , Vômito/epidemiologia , Desequilíbrio Hidroeletrolítico/sangue , Desequilíbrio Hidroeletrolítico/epidemiologia
4.
Horm Metab Res ; 52(2): 89-94, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32053841

RESUMO

Women with PCOS are linked to insulin resistance, inflammation, and vitamin D (VD) deficiency. The study endeavors to comprehend the differential impact of insulin sensitizers vs. anti-androgen on serum leptin levels among women with PCOS rendered vitamin D replete with high VD oral supplement. This was open-labeled randomized study that screened 180 eligible women presenting to Endocrine clinic with oligomenorrhea or features of hyperandrogenism. Ninety-nine women who furnished written informed consent and fulfilled the Rotterdam 2003 criteria for diagnosis of PCOS were randomized into 3 drug treatment arms to receive either spironolactone (50 mg/d; n=30), metformin (1000 mg/d; n=30) or pioglitazone (30 mg/d; n=30). These women were also administered oral VD (4000 IU/day) in addition to the allocated drug for a period of 6 months. Detailed history, clinical examination, and laboratory evaluation was carried out at baseline and 6 months after intervention. Number of menstrual cycles/year increased while as Ferriman-Gallwey score, blood glucose, HOMA-IR, and plasma insulin levels significantly decreased in all the three arms with better outcomes in spironolactone and pioglitazone arms (p<0.05). Similarly, serum leptin levels superiorly improved in spironolactone and pioglitazone group. Pioglitazone group showed better efficacy in lowering serum total testosterone (p<0.05). Co-supplementation of high dosage VD with spironolactone or pioglitazone are more effective in reducing plasma leptin levels than metformin, and thus might prove to be better therapeutic strategies for women with PCOS.


Assuntos
Insulina/sangue , Leptina/sangue , Síndrome do Ovário Policístico/tratamento farmacológico , Vitamina D/sangue , Adulto , Glicemia/metabolismo , Feminino , Humanos , Resistência à Insulina , Metformina/administração & dosagem , Pioglitazona/administração & dosagem , Síndrome do Ovário Policístico/sangue , Espironolactona/administração & dosagem , Testosterona/sangue , Vitamina D/administração & dosagem , Adulto Jovem
5.
J Clin Endocrinol Metab ; 105(3)2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-31730174

RESUMO

CONTEXT: Polycystic ovary syndrome (PCOS) is a prevalent disorder in adolescent girls, purportedly driven by hepato-visceral fat excess, and often followed by subfertility and type 2 diabetes. OBJECTIVE: We studied the baseline microRNA (miRNA) profile of girls with PCOS, and the effects of a randomized treatment with an oral contraceptive (OC) or with spironolactone-pioglitazone-metformin (SPIOMET, aiming at loss of hepato-visceral fat excess) for 1 year. DESIGN & PATIENTS: The miRNA profile was assessed by RNA sequencing in girls with PCOS who had participated in a randomized, open-label, single-center, pilot study (n = 31; age 15.7 years, body mass index (BMI) 23.1 kg/m2). Healthy age- and BMI-matched girls (n = 13) served as controls. Differentially expressed miRNAs were validated by RT-qPCR in the entire study population. Post-treatment ovulation rates were assessed by salivary progesterone in PCOS girls. SETTING: Endocrinology Department, University Hospital. RESULTS: Girls with PCOS, compared with controls, had markedly reduced concentrations of circulating miR-451a, miR-652-3p, miR-106b-5p, and miR-206; pathway enrichment analysis showed that these miRNAs target genes involved in energy homeostasis and cell cycle control. In the present study, miR-451a could diagnose PCOS with 100% sensitivity and 100% specificity. SPIOMET (but not OC) was accompanied by on-treatment normalization of the miRNA profile in girls with PCOS; miR-451a concentrations after 1 year on OC or SPIOMET treatment associated closely (r = 0.66; P < .0001) with post-treatment ovulation rates. CONCLUSION: SPIOMET treatment for 1 year normalizes the miRNA profile of girls with PCOS. Circulating miR-451a may become a biomarker to guide the diagnosis and treatment of PCOS in adolescence.


Assuntos
Anticoncepcionais Orais/administração & dosagem , Hipoglicemiantes/administração & dosagem , MicroRNAs/sangue , Síndrome do Ovário Policístico/sangue , Síndrome do Ovário Policístico/tratamento farmacológico , Adolescente , Biomarcadores/sangue , Quimioterapia Combinada , Feminino , Humanos , Metformina/administração & dosagem , MicroRNAs/efeitos dos fármacos , Projetos Piloto , Pioglitazona/administração & dosagem , Espironolactona/administração & dosagem , Resultado do Tratamento
6.
Mol Pharm ; 17(1): 59-69, 2020 01 06.
Artigo em Inglês | MEDLINE | ID: mdl-31751144

RESUMO

Sustained-release formulations for ocular delivery are of increasing interest given their potential to significantly improve treatment efficacy and patient adherence. The objectives of this study were (i) to develop a sustained-release formulation of spironolactone (SPL) using a biodegradable and injectable polymer, hexyl-substituted poly-lactic acid (hexPLA) and (ii) to investigate the ocular biodistribution and tolerability of SPL and its metabolites in rats in vivo over 1 month following a single intravitreal injection (IVT inj). The concentrations of SPL and its two principal active metabolites, 7α-thiomethylspironolactone and canrenone (CAN), in the different ocular compartments were determined at different time points (3, 7, and 31 days after IVT inj) using a validated ultra-high-performance liquid chromatography-mass spectrometry method. Systemic exposure following a single IVT inj of 5% SPL-hexPLA formulation was evaluated by quantifying SPL and its metabolites in the plasma. Ocular tolerability of the formulation was evaluated using in vivo retinal imaging and histology. In vitro release studies revealed a sustained release of SPL from 5% SPL-hexPLA for up to 65 days. In vivo studies showed that SPL and its metabolites were detected in all ocular tissues at 3 and 7 days post-IVT inj. At 31 days post-IVT inj, SPL and CAN were mainly detected in the retina. These results also highlighted the clearance pathway of SPL and its metabolite involving the anterior and posterior routes in the first week (days 3 and 7), then mainly the posterior segment in the last week (day 31). This study showed that a single IVT inj of 5% SPL-hexPLA in rats enabled sustained delivery of therapeutic amounts of SPL for up to 1 month to the retina without systemic exposure. This formulation may be of interest for the local treatment of diseases involving overactivation of the mineralocorticoid receptor in the chorioretina such as chronic central serous chorioretinopathy.


Assuntos
Poliésteres/química , Retina/metabolismo , Espironolactona/administração & dosagem , Espironolactona/farmacocinética , Animais , Canrenona/química , Cromatografia Líquida , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacocinética , Fundo de Olho , Injeções Intravítreas , Espectrometria de Massas , Ratos , Ratos Wistar , Retina/citologia , Retina/efeitos dos fármacos , Espironolactona/análogos & derivados , Espironolactona/química , Espironolactona/toxicidade , Fatores de Tempo , Distribuição Tecidual , Tomografia de Coerência Óptica
7.
J Clin Pharm Ther ; 45(1): 152-159, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31520539

RESUMO

WHAT IS KNOWN AND OBJECTIVE: Hashimoto's thyroiditis, also referred to as autoimmune thyroiditis, is characterized by sexual dimorphism, suggesting an important role of sex hormones in its development. No interventional study has investigated whether drugs exerting antiandrogen properties affect thyroid antibody titres and thyroid function tests in subjects with autoimmune thyroiditis. METHODS: This study included 35 levothyroxine-naïve men with euthyroid Hashimoto's thyroiditis. At the physician's discretion, 18 men were then treated with spironolactone (50-200 mg daily), while the remaining patients (n = 17) received other diuretics. Serum levels of thyrotropin, free thyroid hormones, testosterone and 25-hydroxyvitamin D, as well as titres of thyroid peroxidase and thyroglobulin, were measured at the beginning of the study and 6 months later. Based on hormone levels, constant structure parameters of thyroid homeostasis were calculated. RESULTS AND DISCUSSION: At baseline, there was no difference between the treatment arms in terms of thyroid antibody titres, hormone levels and the calculated parameters of thyroid homeostasis. Thirty-two patients completed the study. Spironolactone increased thyroid antibody titres, decreased testosterone and 25-hydroxyvitamin D levels and reduced SPINA-GT. The drug produced a neutral effect on serum levels of thyrotropin, free thyroid hormones, Jostel's thyrotropin index and SPINA-GD. The effect of spironolactone on antibody titres correlated with treatment-induced changes in SPINA-GT, testosterone and 25-hydroxyvitamin D. No significant changes in antibody titres, hormone levels and the calculated parameters of thyroid homeostasis were observed in spironolactone-naïve men. WHAT IS NEW AND CONCLUSION: The obtained results indicate that spironolactone may exert an unfavourable effect on progression of autoimmune thyroiditis in men.


Assuntos
Diuréticos/administração & dosagem , Doença de Hashimoto/tratamento farmacológico , Espironolactona/farmacologia , Idoso , Progressão da Doença , Diuréticos/efeitos adversos , Diuréticos/farmacologia , Relação Dose-Resposta a Droga , Doença de Hashimoto/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Espironolactona/administração & dosagem , Espironolactona/efeitos adversos , Testosterona/sangue , Tireoglobulina/sangue , Testes de Função Tireóidea , Hormônios Tireóideos/sangue , Tireotropina/sangue , Vitamina D/análogos & derivados , Vitamina D/sangue
8.
J Gastroenterol Hepatol ; 35(7): 1229-1237, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31881554

RESUMO

BACKGROUND AND AIM: The prognosis of cirrhotic patients with hepatic edema is poor. Although several short-term predictors of tolvaptan (novel diuretic agent) treatment for such patients have been reported, the factors related to long-term survival are still unclear. METHODS: Among 459 patients with hepatic edema enrolled in a retrospective, multicenter collaborative study, we analyzed 407 patients who received tolvaptan. RESULTS: Patients consisted of 266 men and 141 women, with the median age of 68 years (range, 28-93 years). The frequency of short-term responders to tolvaptan was 59.7% (243/407). In the Cox regression analysis, short-term response to tolvaptan, low average dosages of furosemide and spironolactone during tolvaptan treatment, Child-Pugh classification A and B, and absence of hepatocellular carcinoma were independent factors contributed to 1-year survival. The 1-year and long-term cumulative survival rates in short-term responders were significantly higher than those in non-responders (P = 0.011 and 0.010, respectively). Using a receiver operating characteristic curve analysis, the optimal cut-off values of average daily dosages of furosemide and spironolactone for predicting 1-year survival were 19 and 23 mg/day, respectively. The long-term cumulative survival rates in patients who received a mean dosage of spironolactone < 23 mg/day during tolvaptan treatment were significantly higher than those receiving a mean dosage of ≥ 23 mg/day (P = 0.001). CONCLUSIONS: The present study suggests that the short-term response to tolvaptan and low dosages of conventional diuretics during tolvaptan treatment might improve the 1-year and long-term survival rates in cirrhotic patients with hepatic edema.


Assuntos
Edema/tratamento farmacológico , Cirrose Hepática/tratamento farmacológico , Hepatopatias/tratamento farmacológico , Tolvaptan/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Diuréticos/administração & dosagem , Quimioterapia Combinada , Edema/etiologia , Edema/mortalidade , Feminino , Furosemida/administração & dosagem , Humanos , Cirrose Hepática/complicações , Cirrose Hepática/mortalidade , Hepatopatias/etiologia , Hepatopatias/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , Curva ROC , Estudos Retrospectivos , Espironolactona/administração & dosagem , Taxa de Sobrevida , Fatores de Tempo
9.
Am J Clin Dermatol ; 21(1): 13-20, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31494859

RESUMO

BACKGROUND: To date, there have been no studies that have specifically investigated which medications can and cannot be safely used to treat acne vulgaris in patients who have lupus erythematosus (LE). These patients require a highly individualized treatment approach, as the use of certain acne medications may exacerbate LE symptomology, such as photosensitivity and hypercoagulability. OBJECTIVE: In this systematic review, we examine safety outcomes associated with commonly prescribed oral acne medications, specifically in the context of LE. METHODS: A literature search, conducted on PubMed/MEDLINE, revealed 146 studies, of which 13 met the criteria. We assigned a level of evidence to each study and sought to determine evidence-based recommendations for each class of drug; each recommendation was then assigned a corresponding grade. RESULTS: There were very few high-quality studies available on this topic. Although we determined recommendations based on the existing literature, the grading was occasionally unfavorable due to the low-quality nature of the evidence supporting the recommendation. However, our recommendation against the use of combined oral contraceptive pills and in favor of spironolactone for the treatment of acne, in the setting of LE, received a satisfactory grading (grade A). CONCLUSION: While no definitive recommendations for the treatment of acne in LE can be made based on the existing quality and quantity of studies available, this article aims to provide a comprehensive overview and analysis of oral acne medication safety in patients with LE, while emphasizing the immense need for higher quality studies and distinct acne treatment guidelines for this vulnerable patient population.


Assuntos
Acne Vulgar/tratamento farmacológico , Lúpus Eritematoso Sistêmico/complicações , Anticoncepcionais Orais Combinados/administração & dosagem , Anticoncepcionais Orais Combinados/efeitos adversos , Fármacos Dermatológicos/administração & dosagem , Fármacos Dermatológicos/efeitos adversos , Humanos , Espironolactona/administração & dosagem , Espironolactona/efeitos adversos
10.
Pediatr Obes ; 15(2): e12586, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31663293

RESUMO

PCOS is already a prevalent endocrinopathy in adolescent girls, and its prevalence is rising further since, in essence, it is the result of a mismatch between an energy-sparing (epi)genetic background and a (relatively) obesogenic environment. This mismatch results in an excess of fat storage in ectopic depots, notably in the liver and viscera (= hepato-visceral, or central fat). There is still no FDA-approved treatment for adolescent PCOS. The prime aim should be a preferential loss of central fat, through lifestyle measures. Failure to sustain these measures is frequent, and the standard approach is to add an estroprogestagen contraceptive, even for girls who do not need contraception. Treatment with SPIOMET, a low-dose combination of spironolactone (to antagonize androgen and mineralocorticoid effects, and to activate BAT thereby raising energy expenditure), pioglitazone (to raise circulating HMW adiponectin concentrations) and metformin, is an alternative approach that holds the potential to revert the PCOS phenotype.


Assuntos
Síndrome do Ovário Policístico/tratamento farmacológico , Adolescente , Feminino , Humanos , Metformina/administração & dosagem , Pioglitazona/administração & dosagem , Espironolactona/administração & dosagem
12.
Lancet ; 394(10208): 1540-1550, 2019 10 26.
Artigo em Inglês | MEDLINE | ID: mdl-31533906

RESUMO

BACKGROUND: Spironolactone is effective at reducing blood pressure in patients with uncontrolled resistant hypertension. However, the use of spironolactone in patients with chronic kidney disease can be restricted by hyperkalaemia. We evaluated use of the potassium binder patiromer to allow more persistent use of spironolactone in patients with chronic kidney disease and resistant hypertension. METHODS: In this phase 2 multicentre, randomised, double-blind, placebo-controlled study, we enrolled participants aged 18 years and older with chronic kidney disease (estimated glomerular filtration rate 25 to ≤45 mL/min per 1·73 m2) and uncontrolled resistant hypertension from 62 outpatient centres in ten countries (Bulgaria, Croatia, Georgia, Hungary, Ukraine, France, Germany, South Africa, the UK, and the USA). Patients meeting all eligibility criteria at the final screening visit were stratified by local serum potassium measurement (4·3 to <4·7 mmol/L vs 4·7 to 5·1 mmol/L) and history of diabetes. Participants were randomly assigned (1:1) with an interactive web response system to receive either placebo or patiromer (8·4 g once daily), in addition to open-label spironolactone (starting at 25 mg once daily) and their baseline blood pressure medications. Participants, the study team that administered treatments and measured blood pressure, and the investigators were masked to assigned treatment groups. Dose titrations were permitted after 1 week (patiromer) and 3 weeks (spironolactone). The primary endpoint was the between-group difference at week 12 in the proportion of patients on spironolactone. Efficacy endpoints and safety were assessed in all randomised patients (intention to treat). The study was registered with Clinicaltrials.gov, NCT03071263. FINDINGS: Between Feb 13, 2017, and Aug 20, 2018, we screened 574 patients. 295 (51%) of 574 patients met all inclusion criteria and were randomly assigned to spironolactone in addition to double-blind treatment with either placebo (n=148) or patiromer (n=147). At week 12, 98 (66%) of 148 patients in the placebo group and 126 (86%) of 147 patients in the patiromer group remained on spironolactone (between-group difference 19·5%, 95% CI 10·0-29·0; p<0·0001). Adverse events were mostly mild or moderate in severity and occurred in 79 (53%) of 148 patients in the placebo group and 82 (56%) of 147 patients in the patiromer group. INTERPRETATION: In patients with resistant hypertension and chronic kidney disease, patiromer enabled more patients to continue treatment with spironolactone with less hyperkalaemia. Persistent spironolactone enablement in this population of patients has clinical relevance for the treatment of resistant hypertension. FUNDING: Relypsa, a Vifor Pharma Group Company.


Assuntos
Diuréticos/administração & dosagem , Hipertensão/tratamento farmacológico , Polímeros/administração & dosagem , Espironolactona/administração & dosagem , Adulto , Idoso , Diuréticos/efeitos adversos , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Humanos , Hiperpotassemia/prevenção & controle , Hipertensão/complicações , Masculino , Pessoa de Meia-Idade , Potássio/sangue , Insuficiência Renal Crônica/complicações , Espironolactona/efeitos adversos , Resultado do Tratamento
13.
J Am Heart Assoc ; 8(19): e013501, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31549577

RESUMO

Background Duchenne muscular dystrophy incurs nearly universal dilated cardiomyopathy by the third decade of life, preceded by myocardial damage and impaired left ventricular strain by cardiac magnetic resonance. It has been shown that (1) mineralocorticoid receptor antagonist therapy with spironolactone attenuated damage while maintaining function when given early in a mouse model and (2) low-dose eplerenone stabilized left ventricular strain in boys with Duchenne muscular dystrophy and evident myocardial damage but preserved ejection fraction. We hypothesized that moderate-dose spironolactone versus eplerenone would provide similar cardioprotection in this first head-to-head randomized trial of available mineralocorticoid receptor antagonists, the AIDMD (Aldosterone Inhibition in Duchenne Muscular Dystrophy) trial. Methods and Results This was a multicenter, double-blind, randomized, noninferiority trial. Subjects were randomized to eplerenone, 50 mg, or spironolactone, 50 mg, orally once daily for 12 months. The primary outcome was change in left ventricular systolic strain at 12 months. Among 52 enrolled male subjects, aged 14 (interquartile range, 12-18) years, spironolactone was noninferior to eplerenone (∆strain, 0.4 [interquartile range, -0.4 to 0.6] versus 0.2 [interquartile range, -0.2 to 0.7]; P=0.542). Renal and pulmonary function remained stable in both groups, and no subjects experienced serious hyperkalemia. Infrequent adverse events included gynecomastia in one subject in the spironolactone arm and facial rash in one subject in the eplerenone arm. Conclusions In boys with Duchenne muscular dystrophy and preserved left ventricular ejection fraction, spironolactone added to background therapy is noninferior to eplerenone in preserving contractile function. These findings support early mineralocorticoid receptor antagonist therapy as effective and safe in a genetic disease with high cardiomyopathy risk. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT02354352.


Assuntos
Cardiomiopatias/tratamento farmacológico , Eplerenona/administração & dosagem , Antagonistas de Receptores de Mineralocorticoides/administração & dosagem , Distrofia Muscular de Duchenne/complicações , Espironolactona/administração & dosagem , Função Ventricular Esquerda/efeitos dos fármacos , Adolescente , Cardiomiopatias/diagnóstico por imagem , Cardiomiopatias/etiologia , Cardiomiopatias/fisiopatologia , Criança , Método Duplo-Cego , Eplerenona/efeitos adversos , Humanos , Imagem Cinética por Ressonância Magnética , Masculino , Antagonistas de Receptores de Mineralocorticoides/efeitos adversos , Distrofia Muscular de Duchenne/diagnóstico , Contração Miocárdica/efeitos dos fármacos , Espironolactona/efeitos adversos , Volume Sistólico/efeitos dos fármacos , Fatores de Tempo , Resultado do Tratamento , Estados Unidos , Adulto Jovem
14.
J. bras. nefrol ; 41(3): 345-355, July-Sept. 2019. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1040247

RESUMO

ABSTRACT Introduction: There is evidence that aldosterone plays a role in the pathogenesis of vascular calcification. The aim of this study was to evaluate the effect of spironolactone, a mineralocorticoid receptor antagonist, on the progression of coronary calcification (CC) in peritoneal dialysis patients and to identify the factors involved in this progression. Methods: Thirty-three patients with a coronary calcium score (CCS) ≥ 30, detected through multi-detector computed tomography (MDCT) and expressed in Agatston units, were randomly assigned to a group receiving 25mg spironolactone per day for 12 months (spironolactone group) and a control group not receiving this drug. The primary outcome was a percentage change in CCS from baseline to end of the study (relative progression), when a further MDCT was conducted. Patients who had progression of CC were compared with those who did not progress. Results: Sixteen patients, seven in the spironolactone group and nine in the control group, concluded the study. The relative progression of the CCS was similar in both groups, 17.2% and 27.5% in the spironolactone and control groups respectively. Fifty-seven percent of the treated patients and 67% of those in the control group presented progression in the CC scores (p = 0.697). Progressor patients differed from non-progressors because they presented higher levels of calcium and low-density lipoprotein cholesterol and lower levels of albumin. Conclusion: In peritoneal dialysis patients, spironolactone did not attenuate the progression of CC. However, large-scale studies are needed to confirm this observation. Disorders of mineral metabolism and dyslipidemia are involved in the progression of CC.


RESUMO Introdução: Existem evidências de que a aldosterona exerça um papel na patogênese da calcificação vascular. O objetivo deste estudo foi avaliar o efeito da espironolactona, um antagonista do receptor mineralocorticoide, na progressão da calcificação coronariana (CC) de pacientes em diálise peritoneal, e identificar os fatores envolvidos nessa progressão. Métodos: Trinta e três pacientes com escore de cálcio coronariano (ECC) ≥ 30, detectado por tomografia computadorizada com múltiplos detectores (TCMD) e expresso em unidades de Agatston, foram randomizados para um grupo que recebeu 25 mg de espironolactona por dia durante 12 meses (grupo espironolactona) e um grupo controle que não recebeu este medicamento. O desfecho primário foi a mudança percentual do ECC do início para o final do estudo (progressão relativa), quando uma nova TCMD foi realizada. Os pacientes que tiveram progressão de CC foram comparados com aqueles que não progrediram. Resultados: Dezesseis pacientes, sete no grupo espironolactona e nove no grupo controle, concluíram o estudo. A progressão relativa do ECC foi semelhante nos dois grupos, 17,2% e 27,5% nos grupos espironolactona e controle, respectivamente. Cinquenta e sete por cento dos pacientes tratados e 67% daqueles no grupo controle apresentaram progressão nos escores de CC (p = 0,697). Os pacientes progressores diferiram dos não progressores porque apresentaram níveis séricos mais elevados de cálcio e LDL-colesterol e menores níveis de albumina. Conclusão: Em pacientes em diálise peritoneal, a espironolactona não atenuou a progressão da CC. No entanto, estudos em grande escala são necessários para confirmar essa observação. Distúrbios do metabolismo mineral e dislipidemia estão envolvidos na progressão da CC.


Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Espironolactona/uso terapêutico , Diálise Peritoneal , Progressão da Doença , Antagonistas de Receptores de Mineralocorticoides/uso terapêutico , Calcificação Vascular/tratamento farmacológico , Calcificação Vascular/sangue , Espironolactona/administração & dosagem , Tomógrafos Computadorizados , Projetos Piloto , Cálcio/sangue , Estudos Prospectivos , Seguimentos , Resultado do Tratamento , Antagonistas de Receptores de Mineralocorticoides/administração & dosagem , Insuficiência Renal Crônica/terapia , Perda de Seguimento , Calcificação Vascular/patologia , Calcificação Vascular/diagnóstico por imagem , Albumina Sérica Humana/análise , LDL-Colesterol/sangue
15.
J Bras Nefrol ; 41(3): 345-355, 2019 Aug 15.
Artigo em Inglês, Português | MEDLINE | ID: mdl-31419271

RESUMO

INTRODUCTION: There is evidence that aldosterone plays a role in the pathogenesis of vascular calcification. The aim of this study was to evaluate the effect of spironolactone, a mineralocorticoid receptor antagonist, on the progression of coronary calcification (CC) in peritoneal dialysis patients and to identify the factors involved in this progression. METHODS: Thirty-three patients with a coronary calcium score (CCS) ≥ 30, detected through multi-detector computed tomography (MDCT) and expressed in Agatston units, were randomly assigned to a group receiving 25mg spironolactone per day for 12 months (spironolactone group) and a control group not receiving this drug. The primary outcome was a percentage change in CCS from baseline to end of the study (relative progression), when a further MDCT was conducted. Patients who had progression of CC were compared with those who did not progress. RESULTS: Sixteen patients, seven in the spironolactone group and nine in the control group, concluded the study. The relative progression of the CCS was similar in both groups, 17.2% and 27.5% in the spironolactone and control groups respectively. Fifty-seven percent of the treated patients and 67% of those in the control group presented progression in the CC scores (p = 0.697). Progressor patients differed from non-progressors because they presented higher levels of calcium and low-density lipoprotein cholesterol and lower levels of albumin. CONCLUSION: In peritoneal dialysis patients, spironolactone did not attenuate the progression of CC. However, large-scale studies are needed to confirm this observation. Disorders of mineral metabolism and dyslipidemia are involved in the progression of CC.


Assuntos
Progressão da Doença , Antagonistas de Receptores de Mineralocorticoides/uso terapêutico , Diálise Peritoneal , Espironolactona/uso terapêutico , Calcificação Vascular/sangue , Calcificação Vascular/tratamento farmacológico , Idoso , Cálcio/sangue , LDL-Colesterol/sangue , Feminino , Seguimentos , Humanos , Perda de Seguimento , Masculino , Pessoa de Meia-Idade , Antagonistas de Receptores de Mineralocorticoides/administração & dosagem , Projetos Piloto , Estudos Prospectivos , Insuficiência Renal Crônica/terapia , Albumina Sérica Humana/análise , Espironolactona/administração & dosagem , Tomógrafos Computadorizados , Resultado do Tratamento , Calcificação Vascular/diagnóstico por imagem , Calcificação Vascular/patologia
16.
Am J Case Rep ; 20: 1006-1010, 2019 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-31296836

RESUMO

BACKGROUND In the setting of acute decompensated heart failure (ADHF), tolvaptan, a selective V2 receptor antagonist, did not alter plasma renin activity or angiotensin II level, but significantly increased plasma aldosterone by the activation of V1ₐ receptor, suggesting that a high-dose mineralocorticoid receptor antagonist (MRA) combined with a V2 receptor antagonist might be of interest, especially in ADHF patients. However, in the setting of ADHF, the short-term and long-term efficacy of a high-dose MRA combined with tolvaptan remains unclear. CASE REPORT An 86-year-old woman with a history of chronic HF with a preserved ejection fraction due to obstructive hypertrophic cardiomyopathy and severe aortic stenosis was transferred to our hospital complaining of persistent dyspnea (New York Heart Association class IV). She did not respond to standard therapy with tolvaptan (15.0 mg/day). However, the present case demonstrated that adding high-dose spironolactone (100 mg/day) to low-dose tolvaptan (15.0 mg/day) is safe and well tolerated, resulting in an increase in urine output and improvement of the symptoms or signs of ADHF in a patient who was refractory to loop diuretics and tolvaptan. CONCLUSIONS The short- and long-term efficacy of high-dose spironolactone combined with low-dose tolvaptan may be associated with an attenuation of the aldosterone level, which is increased through V1ₐ activation by vasopressin during tolvaptan administration.


Assuntos
Estenose da Valva Aórtica/tratamento farmacológico , Cardiomiopatia Hipertrófica/tratamento farmacológico , Insuficiência Cardíaca/tratamento farmacológico , Espironolactona/administração & dosagem , Tolvaptan/administração & dosagem , Doença Aguda , Idoso de 80 Anos ou mais , Antagonistas dos Receptores de Hormônios Antidiuréticos/administração & dosagem , Estenose da Valva Aórtica/complicações , Cardiomiopatia Hipertrófica/complicações , Quimioterapia Combinada , Dispneia , Feminino , Insuficiência Cardíaca/etiologia , Humanos , Antagonistas de Receptores de Mineralocorticoides/administração & dosagem
17.
J Sex Med ; 16(9): 1481-1483, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31351850

RESUMO

BACKGROUND: Although spironolactone is an effective treatment for androgen-mediated cutaneous disorders, the potential sexual side-effects are poorly documented in current literature. AIM: The purpose of this study was to provide clinical evidence that spironolactone may be a cause of hormonally associated vestibulodynia and female sexual arousal disorder. METHODS: A database search of a vulvar disorders clinic revealed 7 cases in which spironolactone may have caused or contributed to dyspareunia and decreased arousal. In all cases, the patients stopped taking spironolactone and used a compounded estradiol 0.01%/testosterone 0.1% gel to the vestibule twice daily. 2 cases are discussed to further illustrate these previously unreported side effects. OUTCOMES: Improvement in sexual function was determined after treatment. RESULTS: Examination of women taking spironolactone who presented with the complaints of introital dyspareunia revealed vulvar vestibular atrophy and tenderness, especially at the glandular ostia. After stopping spironolactone and applying a topical estrogen/testosterone gel to the vestibule, all women had significant improvement in their vulvar atrophy, resolution of their dyspareunia, and improved sexual arousal. CLINICAL IMPLICATIONS: Use of spironolactone may be a cause of hormonally associated vestibulodynia and female sexual arousal disorder. STRENGTHS AND LIMITATIONS: The influence of spironolactone on vulvar health and sexual function is poorly documented in the medical literature. The strength of this paper is that it examines the potential deleterious side effects of this medication on female sexual function. However, the most significant limitation of this case series is that it was not a prospective, controlled study. CONCLUSIONS: Although treatment of androgen-mediated cutaneous disorders is warranted, medical providers should be aware of the potential sexual side effects of this anti-androgenic medication. Mitchell L, Govind V, Barela K, et al. Spironolactone May be a Cause of Hormonally Associated Vestibulodynia and Female Sexual Arousal Disorder. J Sex Med 2019;16:1481-1483.


Assuntos
Antagonistas de Receptores de Mineralocorticoides/efeitos adversos , Disfunções Sexuais Fisiológicas/induzido quimicamente , Dermatopatias/tratamento farmacológico , Espironolactona/efeitos adversos , Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Antagonistas de Receptores de Mineralocorticoides/administração & dosagem , Comportamento Sexual , Disfunções Sexuais Fisiológicas/fisiopatologia , Espironolactona/administração & dosagem , Resultado do Tratamento
19.
Can J Cardiol ; 35(9): 1097-1105, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31230825

RESUMO

BACKGROUND: Acute heart failure (HF) patients with renal insufficiency and risk factors for diuretic resistance may be most likely to derive incremental improvement in congestion with the addition of spironolactone. METHODS: The Aldosterone Targeted Neurohormonal Combined with Natriuresis Therapy in Heart Failure (ATHENA-HF) trial randomized 360 acute HF patients with reduced or preserved ejection fraction to spironolactone 100 mg daily or usual care for 96 hours. The current analysis assessed the effects of study therapy within tertiles of baseline estimated glomerular filtration rate (eGFR) and subgroups at heightened risk for diuretic resistance. RESULTS: Across eGFR tertiles, there was no incremental benefit of high-dose spironolactone on any efficacy endpoint, including changes in log N-terminal pro-B-type natriuretic peptide and signs and symptoms of congestion (all P for interaction ≥ 0.06). High-dose spironolactone had no significant effect on N-terminal pro-B-type natriuretic peptide reduction regardless of blood pressure, diabetes mellitus status, and loop diuretic dose (all P for interaction ≥ 0.38). In-hospital changes in serum potassium and creatinine were similar between treatment groups for all GFR tertiles (all P for interaction ≥ 0.18). Rates of inpatient worsening HF, 30-day worsening HF, and 60-day all-cause mortality were numerically higher among patients with lower baseline eGFR, but relative effects of study treatment did not differ with renal function (all P for interaction ≥ 0.27). CONCLUSIONS: High-dose spironolactone did not improve congestion over usual care among patients with acute HF, irrespective of renal function and risk factors for diuretic resistance. In-hospital initiation or continuation of spironolactone was safe during the inpatient stay, even when administered at high doses to patients with moderate renal dysfunction.


Assuntos
Resistência a Medicamentos , Taxa de Filtração Glomerular/fisiologia , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Renal/complicações , Espironolactona/administração & dosagem , Creatinina/sangue , Relação Dose-Resposta a Droga , Seguimentos , Taxa de Filtração Glomerular/efeitos dos fármacos , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/fisiopatologia , Humanos , Antagonistas de Receptores de Mineralocorticoides/administração & dosagem , Estudos Prospectivos , Insuficiência Renal/sangue , Insuficiência Renal/fisiopatologia , Fatores de Risco , Volume Sistólico/fisiologia , Resultado do Tratamento
20.
J Investig Med High Impact Case Rep ; 7: 2324709619850215, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31113263

RESUMO

BACKGROUND: Pathological causes of acne and hirsutism include polycystic ovarian syndrome (PCOS), congenital adrenal hyperplasia, and adrenal or ovarian tumors. PCOS is largely a clinical diagnosis and often simple laboratory testing can rule out more severe pathology. In more severe cases, determination of the correct diagnosis can require hormone suppression testing. In this article, we present a full sequence of hormone suppression testing and workup necessary to arrive at the ultimate diagnosis. CASE PRESENTATION: A 12-year-old normal weight (body mass index = 29th percentile), premenarchal female with Tanner III breast, Tanner V pubic hair presented with a 2.5-year history of severe hirsutism (Ferriman-Gallwey Score of 22), clitoromegaly, and deep voice. Successive hormone suppression and testing (ACTH stimulation testing, ovarian and adrenal imaging, dexamethasone-suppressed ACTH stimulation testing, and oral contraceptive therapy) was necessary to rule out congenital adrenal hyperplasia or a tumor and confirm PCOS. Metabolic testing, completed only after diagnosing PCOS, demonstrated insulin resistance. CONCLUSIONS: This patient had an extreme presentation of a common disorder. Her premenarchal status, elevated androgens, and virilization raised concern for non-PCOS pathology requiring sequential pharmacological hormone suppression testing and imaging for accurate diagnosis and appropriate treatment. The testing presented here is not novel, but we present the full sequence of testing and clinical results. This full sequence is rarely necessary for accurate diagnosis given clinical presentation and initial evaluation and, therefore, to our knowledge, has not been published. All providers caring for patients with PCOS should be familiar with this testing and its interpretation for severe cases that warrant extra attention.


Assuntos
Hiperandrogenismo/diagnóstico , Síndrome do Ovário Policístico/diagnóstico , Síndrome do Ovário Policístico/tratamento farmacológico , Criança , Anticoncepcionais Orais/administração & dosagem , Estrogênios/administração & dosagem , Feminino , Hirsutismo/etiologia , Humanos , Hiperandrogenismo/complicações , Hiperandrogenismo/fisiopatologia , Resistência à Insulina , Distúrbios Menstruais , Síndrome do Ovário Policístico/complicações , Espironolactona/administração & dosagem , Virilismo/etiologia
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