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1.
Nephrol Dial Transplant ; 34(Suppl 3): iii45-iii50, 2019 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-31800078

RESUMO

Hyperkalemia represents a common and potentially life-threating electrolyte abnormality, a complication frequently observed in patients with heart failure, kidney disease, diabetes or in those receiving drug therapies influencing the renin-angiotensin-aldosterone system. Elevated serum potassium levels are often the result of impaired urinary potassium elimination, inadequate or reduced cellular potassium uptake, severe heart failure, use of medications influencing potassium levels in the circulation, or, more commonly, a combination of these factors. Strategies for the treatment of nonemergent hyperkalemia include the use of cation-exchange resins, polymers or other novel mechanisms of potassium trapping, including sodium polystyrene sulfonate, patiromer and sodium zirconium cyclosilicate. These agents differ in their pharmacology and mechanism of action, clinical efficacy, including onset and extent of potassium-lowering effect, dosage and administration, and potential safety and adverse effect profiles. In this review, an evaluation of these characteristics, including clinical evidence and safety concerns, in the management of nonemergent hyperkalemia will be explored.


Assuntos
Hiperpotassemia/tratamento farmacológico , Antagonistas de Receptores de Mineralocorticoides/administração & dosagem , Poliestirenos/administração & dosagem , Potássio/sangue , Silicatos/administração & dosagem , Quelantes/administração & dosagem , Relação Dose-Resposta a Droga , Humanos , Hiperpotassemia/sangue , Sistema Renina-Angiotensina/efeitos dos fármacos , Sistema Renina-Angiotensina/fisiologia , Resultado do Tratamento
2.
Ophthalmic Surg Lasers Imaging Retina ; 50(11): 726-733, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31755972

RESUMO

BACKGROUND AND OBJECTIVE: To evaluate the efficacy and safety of oral eplerenone in the treatment of acute and chronic central serous chorioretinopathy (CSCR). PATIENTS AND METHODS: Treatment-naïve patients with acute (< 3 months) and chronic (≥ 3 months) CSCR were enrolled in this prospective, nonrandomized, interventional, comparative case series. Patients with acute CSCR were either treated with oral eplerenone (acute case group; n = 16) or observed only (acute control group; n = 8). All chronic patients (chronic group; n = 25) were treated with oral eplerenone. Eplerenone was prescribed 25 mg twice per day for 3 months. Best-corrected visual acuity (BCVA) and optical coherence tomography measures, including subretinal fluid (SRF) height, subfoveal choroidal thickness (CT), central CT, central choroidal volume (CV), and total CV, were assessed at baseline and 3-month follow-up (FU) visit. RESULTS: BCVA improvement and SRF reduction at 3-month FU relative to baseline were observed in all three study groups. SRF was completely resolved in 13 patients (81.2%) in the acute case group, four patients (50%) in the acute control group, and eight patients (32%) in the chronic group. The acute case group showed greater SRF decrease relative to baseline compared to the chronic group (P = .009), but the resolution of SRF between acute cases and an acute control group was not statistically significant (P = .076). Subfoveal CT, central CT, total CV, and central CV were significantly reduced at the 3-month FU compared to baseline in both affected and the fellow eyes in the acute case and chronic groups, whereas no change was observed in either eyes in the acute control group. At 3 months' FU, the mean logMAR visual acuity demonstrated no significant difference among the study groups (P = .08). Eplerenone was well-tolerated, and no serious side effect was detected. CONCLUSIONS: Oral eplerenone is a safe and effective treatment option for both acute and chronic CSCR. Resolution of SRF was more significant in acute CSR cases comparative to chronic cases. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:726-733.].


Assuntos
Coriorretinopatia Serosa Central/tratamento farmacológico , Eplerenona/administração & dosagem , Antagonistas de Receptores de Mineralocorticoides/administração & dosagem , Administração Oral , Adulto , Coriorretinopatia Serosa Central/patologia , Coriorretinopatia Serosa Central/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Tomografia de Coerência Óptica , Acuidade Visual/fisiologia
3.
Clin Cardiol ; 42(11): 1106-1112, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31482613

RESUMO

BACKGROUND: Trials using mineralocorticoid receptor antagonists (MRAs) in myocardial infraction (MI) without heart failure (HF) or systolic impairment have been underpowered to assess morbidity-mortality benefit. In EPHESUS 6632 patients were included, of whom 11% had an ejection fraction (EF) of 40% and HF or diabetes. We aim to assess the potential benefit of MRAs in MI with EF of 40%. METHODS: Cox models with interaction term for EF. The primary outcome was a composite of cardiovascular death or hospitalization for cardiovascular reasons. HYPOTHESIS: Patients with an EF of 40% benefit similarly from MRA therapy to those with an EF <40%. RESULTS: In EPHESUS, 753 patients had an EF = 40% and 5864 an EF < 40%. Patients with an EF = 40% were younger (63 vs 64 years), had lower heart rate (73 vs 75 bpm), less atrial fibrillation (10% vs 14%), previous MI (21% vs 28%), HF hospitalization (5% vs 8%), and had more often reperfusion therapy and/or revascularization (55% vs 44%). The mean EF was 40.0 ± 0.3% in those with EF = 40% vs 32.2 ± 5.9% in those with EF < 40%. The primary outcome occurred in 13.3% (10 events per 100 py) of the patients with EF = 40% vs 22.9% (19 events per 100 py) in those with EF < 40%; adjusted HR for EF = 40% vs <40% = 0.65 (0.53-0.81). Eplerenone reduced the event-rate homogenously regardless of EF (interaction p EF = 40% vs EF < 40% = 0.21). Similar findings were observed for cardiovascular and all-cause death. CONCLUSION: Eplerenone reduces hospitalizations and mortality in patients with MI and EF = 40% similarly to patients with EF < 40%. These findings suggest that MI patients with EF in the "mid-range zone" may also benefit from MRA therapy which might help clinicians in their treatment decisions.


Assuntos
Eplerenona/administração & dosagem , Infarto do Miocárdio/tratamento farmacológico , Volume Sistólico/fisiologia , Função Ventricular Esquerda/fisiologia , Causas de Morte/tendências , Relação Dose-Resposta a Droga , Feminino , França/epidemiologia , Hospitalização/tendências , Humanos , Masculino , Pessoa de Meia-Idade , Antagonistas de Receptores de Mineralocorticoides/administração & dosagem , Morbidade/tendências , Infarto do Miocárdio/epidemiologia , Infarto do Miocárdio/fisiopatologia , Volume Sistólico/efeitos dos fármacos , Taxa de Sobrevida/tendências , Resultado do Tratamento , Função Ventricular Esquerda/efeitos dos fármacos
4.
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
5.
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
6.
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
7.
Semin Ophthalmol ; 34(6): 436-441, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31309849

RESUMO

Purpose: To evaluate the efficacy and safety of oral eplerenone in cases of central serous chorioretinopathy (CSCR) refractory to photodynamic therapy (PDT). Methods: 19 patients with chronic CSCR and persistent subretinal fluid (SRF) were treated with oral eplerenone for 6 months, starting at a dose of 25 mg/day for 4 weeks and then 50 mg/day for 5 months. All patients underwent visual acuity measurement and optical coherence tomography (OCT), while fluorescein angiography was also performed at baseline, before treatment. Resolution of SRF, changes in retinal thickness and BCVA changes at month 6 and 12 post-treatment initiation were assessed. In addition, creatinine and electrolyte test was done on each patient every month for potential complications. Results: Two out of 19 cases were excluded, since one presented with hyperkaliemia 15 days after eplerenone intake and one with skin rash one day after the treatment initiation. At month 12, 88.2% of patients exhibited visual acuity improvement and 76.4% SRF resolution, while in 11.8% of patients SRF remained stable. Conclusions: This study has shown that eplerenone is safe and effective in cases of chronic CSCR, refractory to previous PDT.


Assuntos
Coriorretinopatia Serosa Central/tratamento farmacológico , Eplerenona/administração & dosagem , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/uso terapêutico , Acuidade Visual/fisiologia , Administração Oral , Adulto , Coriorretinopatia Serosa Central/diagnóstico , Coriorretinopatia Serosa Central/fisiopatologia , Corioide/patologia , Doença Crônica , Relação Dose-Resposta a Droga , Feminino , Angiofluoresceinografia , Seguimentos , Fundo de Olho , Humanos , Masculino , Pessoa de Meia-Idade , Antagonistas de Receptores de Mineralocorticoides/administração & dosagem , Estudos Prospectivos , Retina/patologia , Tomografia de Coerência Óptica , Resultado do Tratamento
8.
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
9.
J Neurol ; 266(7): 1623-1632, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30937521

RESUMO

We report a young wheelchair-dependent patient with an unclear proximal myopathy and a heterozygous, de-novo Cav1.1-R1239G mutation suggesting hypokalemic periodic paralysis (HypoPP). Sonography showed a loss of the pennate pattern indicative of an edema, whereas fatty degeneration was excluded. Within 7 days of therapy with spironolactone, potassium and physical therapy, muscle strength almost completely normalized, a normal pennate pattern appeared and the edema was markedly reduced. She learned to walk without aid and to do sports and has continued to do so for 11 years until now. Over the years, we tested serum potassium values, muscle strength, muscle edema and muscular sodium content by 1.5 T, 3 T and 7 T 1H and 23Na magnetic resonance imaging. No fatty muscle degeneration developed. Muscular edema-like changes only occurred when she was pregnant and was set to reduced therapy. Because of the ability to do sports again, her mobility was further increased. Our observational study on this single patient may suggest that: (1) muscle imaging and molecular genetics are important diagnostic tools, (2) weakness in periodic paralysis may be reversible, and (3) continued adequate therapy may preserve muscle structure and strength on a longterm, whereas weakness due to fatty degeneration could be considered progressive and irreversible. Although HypoPP is a rare disease, it should be included in differential diagnosis not only if there is paroxysmal weakness, but also in cases of myopathy of unknown origin.


Assuntos
Canais de Cálcio Tipo L , Paralisia Periódica Hipopotassêmica/diagnóstico por imagem , Paralisia Periódica Hipopotassêmica/tratamento farmacológico , Força Muscular/efeitos dos fármacos , Músculo Esquelético/diagnóstico por imagem , Espironolactona/administração & dosagem , Adulto , Canais de Cálcio Tipo L/genética , Feminino , Humanos , Paralisia Periódica Hipopotassêmica/genética , Antagonistas de Receptores de Mineralocorticoides/administração & dosagem , Força Muscular/fisiologia , Potássio/administração & dosagem , Fatores de Tempo
10.
Medicine (Baltimore) ; 98(13): e15033, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30921227

RESUMO

RATIONALE: Cases of adrenocortical hyperfunction combined with primary aldosteronism have been reported in the literature, and the underlying mechanism involves the secretion of aldosterone and glucocorticoids by a tumor or an adenoma. However, adrenocortical hypofunction and coexisting primary aldosteronism have not been reported until now. Herein, we report a case of adrenocortical hypofunction combined with primary aldosteronism. PATIENT CONCERNS: A 66-year-old Chinese woman with rheumatoid arthritis who had been diagnosed with secondary adrenal insufficiency and was taking prednisone acetate tablets for replacement treatment presented to our department. She also had type 2 diabetes mellitus, osteoporosis, bilateral knee osteoarthritis, and lumbar vertebral compression fracture. She had previously developed tuberculosis, which had been cured. DIAGNOSIS: The cortisol and adrenocorticotropic hormone rhythm indicated cortisol dysfunction in the patient. A 64-slice computed tomography and magnetic resonance imaging both showed bilateral adrenal hyperplasia. A postural stimulation test indicated a high level of aldosteronism and a high aldosterone-to-renin ratio (ARR, supine position: aldosterone 1788.73 pg/mL, ARR 146.62; upright position: aldosterone 2916.21 pg/mL, ARR 92.29). The captopril test showed the aldosterone level decreased by 364.70 pg/mL 1 hour after administration of captopril (from 2153.28 to 1788.58 pg/mL). The decline in aldosterone level was approximately 16.90% (i.e., <30%), and the ARR was still >40. Based on the above-mentioned findings, we diagnosed the patient with adrenocortical hypofunction with primary aldosteronism. INTERVENTIONS: We administered spironolactone 20 mg twice daily and continued the glucocorticoid replacement therapy. OUTCOMES: One week after diagnosis, the patient had an aldosterone level of 2201.16 pg/mL, plasma renin activity of 3.88 ng/mL/h, and an ARR of 56.7 (upright position). Her blood pressure was maintained within the normal range. LESSONS: Although adrenocortical hypofunction with primary aldosteronism is rare, cases of primary aldosteronism complicated with hypercortisolism are occasionally encountered. Hence, whenever possible, we recommend testing both aldosterone and cortisol levels in all patients with adrenal dysfunction.


Assuntos
Insuficiência Adrenal/complicações , Síndrome de Cushing/complicações , Hiperaldosteronismo/complicações , Insuficiência Adrenal/metabolismo , Idoso , Aldosterona/análise , Síndrome de Cushing/metabolismo , Feminino , Humanos , Hidrocortisona/análise , Hiperaldosteronismo/tratamento farmacológico , Hiperaldosteronismo/metabolismo , Antagonistas de Receptores de Mineralocorticoides/administração & dosagem , Espironolactona/administração & dosagem
12.
Kidney Int ; 95(4): 983-991, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30712923

RESUMO

Mineralocorticoid receptor antagonists have beneficial effects on left ventricular remodeling, cardiac fibrosis, and arrhythmia in heart failure, but efficacy and safety in dialysis patients is less clear. We evaluated the effect of spironolactone on left ventricular mass (LVM), an independent predictor of all-cause and cardiovascular mortality, in hemodialysis patients. In this placebo-controlled, parallel-group trial, 97 hemodialysis patients (23% female; mean age 60.3 years) were randomized to spironolactone 50 mg once daily (n=50) or placebo (n=47). The primary efficacy endpoint was change in LVM index (LVMi) from baseline to 40 weeks as determined by cardiac magnetic resonance imaging. Safety endpoints were development of hyperkalemia and change in residual renal function. There was no significant change in LVMi in participants randomized to spironolactone compared to placebo (-2.86±11.87 vs. 0.41±10.84 g/m2). There was also no difference in the secondary outcomes of mean 24-hour systolic or diastolic ambulatory blood pressure, left ventricular ejection fraction, 6-minute walk test distance, or New York Heart Association functional class. Moderate hyperkalemia (pre-dialysis potassium levels of 6.0-6.5 mmol/L) was more frequent with spironolactone treatment (155 vs. 80 events), but severe hyperkalemia (≥6.5 mmol/L) was not (14 vs. 24 events). Changes in residual urine volume and measured glomerular filtration rate did not differ between groups. There were no deaths in the spironolactone group and 4 deaths in the placebo group. Thus, treatment with 50 mg spironolactone did not change left ventricular mass index, cardiac function, or blood pressure in hemodialysis patients. Spironolactone increased the frequency of moderate hyperkalemia, but did not increase severe hyperkalemia.


Assuntos
Insuficiência Cardíaca/prevenção & controle , Ventrículos do Coração/patologia , Antagonistas de Receptores de Mineralocorticoides/administração & dosagem , Espironolactona/administração & dosagem , Remodelação Ventricular/efeitos dos fármacos , Idoso , Método Duplo-Cego , Feminino , Insuficiência Cardíaca/etiologia , Ventrículos do Coração/diagnóstico por imagem , Ventrículos do Coração/efeitos dos fármacos , Humanos , Hiperpotassemia/induzido quimicamente , Hiperpotassemia/epidemiologia , Falência Renal Crônica/complicações , Falência Renal Crônica/terapia , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Antagonistas de Receptores de Mineralocorticoides/efeitos adversos , Placebos/administração & dosagem , Placebos/efeitos adversos , Diálise Renal , Espironolactona/efeitos adversos , Volume Sistólico/efeitos dos fármacos , Resultado do Tratamento
14.
Eur J Heart Fail ; 21(3): 345-351, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30768732

RESUMO

BACKGROUND: Current heart failure guidelines recommend target eplerenone dose of 50 mg/day. We have examined the effect of different eplerenone doses based on pre-specified renal function stratification in the Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure (EMPHASIS-HF). METHODS AND RESULTS: In EMPHASIS-HF, the target dose of eplerenone/placebo was stratified at randomization according to estimated glomerular filtration rate (eGFR): 50 mg/day if eGFR ≥ 50 mL/min/1.73 m2 and ≤ 25 mg/day if eGFR 30-49 mL/min/1.73 m2 . Patients remained within these dose ranges during the trial (as per stratification). The primary outcome was a composite of heart failure hospitalization or cardiovascular mortality. Eplerenone was superior to placebo within each respective eGFR stratum [eplerenone vs. placebo in the eGFR ≥ 50 mL/min/1.73 m2 stratum: hazard ratio (HR) 0.58, 95% confidence interval (CI) 0.45-0.74; and eplerenone vs. placebo in the eGFR 30-49 mL/min/1.73 m2 stratum: HR 0.62, 95% CI 0.49-0.78; Pinteraction = 0.89]. Despite receiving lower eplerenone doses, patients in the eGFR 30-49 mL/min/1.73 m2 stratum more often had hyperkalaemia, renal failure events, and drug discontinuation. CONCLUSION: In EMPHASIS-HF the eplerenone dose was stratified according to renal function and the treatment effect was not influenced by renal function: 25 mg/day in patients with eGFR 30-49 mL/min/1.73 m2 was as effective as 50 mg/day in patients with eGFR > =50 mL/min/1.73 m2 . However, patients with impaired renal function experienced more adverse events, despite reveiving lower eplerenone doses. Current guidelines do not recommend tailoring the dose of eplereone according to renal function but the current data suggest they should.


Assuntos
Relação Dose-Resposta a Droga , Eplerenona , Taxa de Filtração Glomerular/efeitos dos fármacos , Insuficiência Cardíaca , Testes de Função Renal , Idoso , Disponibilidade Biológica , Monitoramento de Medicamentos/métodos , Eplerenona/administração & dosagem , Eplerenona/efeitos adversos , Eplerenona/farmacocinética , Feminino , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/fisiopatologia , Hospitalização/estatística & dados numéricos , Humanos , Testes de Função Renal/métodos , Testes de Função Renal/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Antagonistas de Receptores de Mineralocorticoides/administração & dosagem , Antagonistas de Receptores de Mineralocorticoides/efeitos adversos , Antagonistas de Receptores de Mineralocorticoides/farmacocinética , Farmacovigilância , Resultado do Tratamento
15.
Pediatr Obes ; 14(5): e12500, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30653851

RESUMO

S100A4 is a marker of subcutaneous adipose tissue dysfunction. Polycystic ovary syndrome (PCOS) is often driven by hepato-visceral adiposity. PCOS phenotypes are normalized more by reduction of central fat with spironolactone/pioglitazone/metformin (SPIOMET) than by oral contraceptive (OC) treatment. We studied whether circulating S100A4 concentrations are high in adolescents with PCOS and, if so, whether they normalize more with OC or SPIOMET. Assessments included circulating S100A4, endocrine markers, body composition, abdominal fat partitioning in controls (n = 12) and girls with PCOS (n = 51; age 15.8 y; body mass index [BMI] 24.5 kg/m2 ), and 1-year changes in girls with PCOS randomized for OC (n = 27) or SPIOMET (n = 24) treatment. Mean S100A4 concentrations were 71% higher (P < 0.001) in girls with PCOS than in controls and associated with hepato-visceral adiposity (r = 0.47; P = 0.001); S100A4 concentrations decreased more (P < 0.01) with SPIOMET, those decreases associating to hepato-visceral fat loss (r = 0.50; P < 0.0001). S100A4 may become a circulating marker of hepato-visceral fat excess in adolescents with PCOS.


Assuntos
Anticoncepcionais Orais/uso terapêutico , Hipoglicemiantes/administração & dosagem , Gordura Intra-Abdominal/fisiopatologia , Antagonistas de Receptores de Mineralocorticoides/administração & dosagem , Síndrome do Ovário Policístico/sangue , Proteína A4 de Ligação a Cálcio da Família S100/sangue , Adolescente , Adulto , Biomarcadores/sangue , Índice de Massa Corporal , Quimioterapia Combinada , Feminino , Humanos , Gordura Intra-Abdominal/efeitos dos fármacos , Metformina/administração & dosagem , Pioglitazona/administração & dosagem , Síndrome do Ovário Policístico/tratamento farmacológico , Síndrome do Ovário Policístico/fisiopatologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Espironolactona/administração & dosagem
16.
Curr Hypertens Rep ; 21(1): 5, 2019 01 18.
Artigo em Inglês | MEDLINE | ID: mdl-30659374

RESUMO

PURPOSE OF REVIEW: Hypertension and antihypertensive drug utilization are remarkably prevalent in ESRD patients. Management of blood pressure elevation in this population is complicated by many factors, including a multidimensional etiology, challenges in obtaining accurate and appropriately timed blood pressure measurements, highly specific drug dosing requirements, and a paucity of outcomes-based evidence to guide management decisions. The purpose of this review is to summarize and apply knowledge from existing clinical trials to enhance safe and effective use of antihypertensive agents in dialysis patients. RECENT FINDINGS: Two meta-analyses have established the benefit of antihypertensive therapy in ESRD. Data supporting the use of one antihypertensive class over another is less robust; however, beta-blockers have more clearly demonstrated improved cardiovascular outcomes in prospective randomized trials. Interdialytic home blood pressure monitoring has been demonstrated to be better associated with cardiovascular outcomes than clinic pre- or post-dialysis readings and should ideally be considered as a routine part of blood pressure management in this population. As data from small trials provides limited guidance for the management of hypertension in ESRD, more research is needed to guide medication selection and utilization. Specifically, large prospective randomized trails comparing cardiovascular outcomes of various medication classes and differing blood pressure targets are needed.


Assuntos
Anti-Hipertensivos/administração & dosagem , Hipertensão/tratamento farmacológico , Falência Renal Crônica/terapia , Diálise Renal , Antagonistas de Receptores Adrenérgicos alfa 2/administração & dosagem , Antagonistas de Receptores Adrenérgicos alfa 2/farmacocinética , Antagonistas Adrenérgicos beta/administração & dosagem , Antagonistas Adrenérgicos beta/farmacocinética , Antagonistas de Receptores de Angiotensina/administração & dosagem , Antagonistas de Receptores de Angiotensina/farmacocinética , Inibidores da Enzima Conversora de Angiotensina/administração & dosagem , Inibidores da Enzima Conversora de Angiotensina/farmacocinética , Anti-Hipertensivos/farmacocinética , Determinação da Pressão Arterial , Bloqueadores dos Canais de Cálcio/administração & dosagem , Bloqueadores dos Canais de Cálcio/farmacocinética , Relação Dose-Resposta a Droga , Humanos , Hipertensão/complicações , Falência Renal Crônica/complicações , Antagonistas de Receptores de Mineralocorticoides/administração & dosagem , Antagonistas de Receptores de Mineralocorticoides/farmacocinética , Vasodilatadores/administração & dosagem , Vasodilatadores/farmacocinética
17.
Clin Res Cardiol ; 108(7): 806-814, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30604047

RESUMO

BACKGROUND: Increased resting heart rate is a risk factor for cardiovascular mortality and morbidity. Mineralocorticoid receptor antagonists (MRAs) have been shown to improve cardiac sympathetic nerve activity, reduce heart rate and attenuate left ventricular remodelling. Whether or not the beneficial effects of MRA are affected by heart rate in heart failure patients with reduced ejection fraction (HFREF) is unclear. METHODS: We undertook a secondary analysis of data from the Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure study to assess if clinical outcomes, as well as the efficacy of eplerenone, varied according to heart rate at baseline. RESULTS: High resting heart rate of 80 bpm and above predisposed patients to greater risk of all outcomes in the trial, regardless of treatment allocation. The beneficial effects of eplerenone were observed across all categories of heart rate. Eplerenone reduced the risk of primary endpoint, the composite of cardiovascular death and hospitalisation for heart failure, by 30% (aHR 0.70; 95% CI 0.54-0.91) in subjects with heart rate ≥ 80 bpm, and by 48% (aHR 0.52; 95% CI 0.33-0.81) in subjects with heart rate ≤ 60 bpm. Eplerenone also reduced the risks of hospitalisation for heart failure, cardiovascular deaths and all-cause deaths independently of baseline heart rate. CONCLUSIONS: Baseline heart rate appears to be an important predictor of major clinical outcome events in patients with HFREF, as has been previously reported. The benefits of eplerenone were preserved across all categories of baseline heart rate, without observed heterogeneity in the responses.


Assuntos
Eplerenona/administração & dosagem , Insuficiência Cardíaca Sistólica/tratamento farmacológico , Frequência Cardíaca/efeitos dos fármacos , Volume Sistólico/fisiologia , Relação Dose-Resposta a Droga , Europa (Continente)/epidemiologia , Feminino , Insuficiência Cardíaca Sistólica/mortalidade , Insuficiência Cardíaca Sistólica/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Antagonistas de Receptores de Mineralocorticoides/administração & dosagem , Fatores de Risco , Taxa de Sobrevida/tendências , Resultado do Tratamento , Estados Unidos/epidemiologia
18.
Med. clín (Ed. impr.) ; 152(2): 50-54, ene. 2019. graf, tab
Artigo em Espanhol | IBECS | ID: ibc-181819

RESUMO

Introducción: La insuficiencia cardiaca (IC) con fracción de eyección (FE) recuperada está emergiendo como un subtipo de IC diferenciada. Existe poca información sobre su perfil clínico en centros que no son referencia. Métodos: Analizamos la evolución y pronóstico de los pacientes afectos de IC con FE recuperada seguidos prospectivamente en una unidad de IC de un hospital no terciario. Resultados: Se ha seguido a 431 pacientes con FE deprimida (mediana 50 meses; edad media de 70,3±12,2 años; el 79,3% eran varones.) El 26,9% normalizaron la FEVI; el 76,7% de ellos en el primer año. Comparados con los pacientes que no normalizaron la FEVI, eran más jóvenes, el origen isquémico de la IC era menos frecuente y presentaban menos comorbilidad. Su pronóstico es mejor (mediana de supervivencia 85,2± 2,1vs. 74,2± 1,9 meses, log-rank χ2 11,5; p = 0,001; hazard ratio de 0,37, intervalo de confianza [IC] del 95%: 0,21-0,67; p = 0,002). Las causas de muerte principalmente no estaban relacionadas con IC. Las variables predictoras de normalización de la FEVI fueron la edad (odds ratio [OR] para más de 69 años 0,98; IC 95%: 0,96-0,99; p = 0,025), origen no isquémico (OR 1,12; IC 95%: 1,01-1,21; p = 0,003) y prescripción de antialdosterónicos (OR 1,89; IC 95%: 1,05-3,26; p = 0,023). Conclusión: La normalización de la FE en pacientes con IC con FE reducida es frecuente y presenta unas características basales, evolución y pronóstico más favorables que la IC con persistencia de FE reducida. Investigaciones futuras deberán confirmar su historia natural y tratamiento óptimo


Introduction: Heart failure (HF) with recovered ejection fraction (EF) is emerging as a different HF subtype. There is little information about his clinical profile in hospitals that are not a reference. Methods: We analysed characteristics and prognosis in patients with recovered HF followed prospectively in the HF Unit of a non-tertiary hospital. Results: A total of 431 patients with HF with reduced EF were followed (median 50 months, 79.3% males, mean age 70.3±12.2years). Of the patients, 26.9% (N 116) recovered EF, mainly in the first year of follow-up (76.7%). Compared with patients that did not recovered EF in the follow-up, they were younger, rate of ischemic origin of cardiomyopathy was less frequent and presented less comorbidity. Mortality was lower in patients with recovered HF (survival median of 85.2±2.1 vs. 74.2±1.9 months [log-rank χ2 11.5, P=0.001], hazard ratio 0.37, 95% confidence interval [CI]: 0.21-0.67, P=0.002). Aetiology of deaths was not mainly secondary to HF. Younger age of 68 years (odds ratio [OR] 0-98, 95% CI: 0.96-0,99; P=0.025), ischemic origin (OR 1.12, 95% CI: 1.01-1.21; P=0.003) and use of aldosterone antagonists (OR 1.89, 95% CI: 1.09-3.26; P=0.023) were the variables independently associated to normalisation of EF. Conclusion: HF with recovered EF is a frequent phenomenon. It has a more favourable clinical course, prognosis and basal characteristics than HF with persistent reduced EF. Further studies are needed to identify natural history and optimal medications for HF-recovered patients


Assuntos
Humanos , Masculino , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Insuficiência Cardíaca Sistólica/diagnóstico , Prognóstico , Volume Sistólico , Antagonistas de Receptores de Mineralocorticoides/administração & dosagem , Estudos Prospectivos , Razão de Chances , Insuficiência Cardíaca/etiologia , Modelos Logísticos
19.
Ann Vasc Surg ; 56: 103-107, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30342208

RESUMO

BACKGROUND: Postoperative fluid overload in cardiovascular surgery is associated with increased mortality and morbidity. Recently, tolvaptan (TLV), a selective vasopressin V2 antagonist, has been used for perioperative fluid management. This study aimed to validate the safety and effectiveness of TLV administration after total arch replacement (TAR) using selective cerebral perfusion. METHODS: From August 2016 to December 2016, 11 patients who had undergone TAR for thoracic aortic aneurysm were included in this study. In addition to the conventional diuretics furosemide (20 mg) and spironolactone (25 mg), TLV (7.5 mg) was administered orally. RESULTS: TLV increased urine output 1-3 days after administration. Body weight was gradually and steadily reduced until discharge. Neither renal nor liver dysfunction was recognized during the TLV administration. CONCLUSION: The concomitant use of TLV and conventional diuretics is safe and effective for fluid management after TAR using cardiopulmonary bypass, selective cerebral perfusion, and hypothermic circulatory arrest.


Assuntos
Antagonistas dos Receptores de Hormônios Antidiuréticos/administração & dosagem , Aneurisma da Aorta Torácica/cirurgia , Implante de Prótese Vascular , Tolvaptan/administração & dosagem , Micção/efeitos dos fármacos , Equilíbrio Hidroeletrolítico/efeitos dos fármacos , Administração Oral , Idoso , Antagonistas dos Receptores de Hormônios Antidiuréticos/efeitos adversos , Aneurisma da Aorta Torácica/diagnóstico por imagem , Implante de Prótese Vascular/efeitos adversos , Esquema de Medicação , Quimioterapia Combinada , Feminino , Furosemida/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Antagonistas de Receptores de Mineralocorticoides/administração & dosagem , Estudos Retrospectivos , Inibidores de Simportadores de Cloreto de Sódio e Potássio/administração & dosagem , Espironolactona/administração & dosagem , Fatores de Tempo , Tolvaptan/efeitos adversos , Resultado do Tratamento , Perda de Peso/efeitos dos fármacos
20.
Br J Ophthalmol ; 103(8): 1184-1189, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30355720

RESUMO

AIMS: To evaluate the long-term oral mineralocorticoid receptor antagonist (MRa) treatment in chronic central serous chorioretinopathy (CSC). METHODS: Patients with chronic non-resolving CSC (defined as foveal subretinal fluid (SRF) lasting >4 months with retinal pigment epithelium (RPE) alterations) treated with MRa only (eplerenone or spironolactone) for at least 6 months were retrospectively included. Clinical and imaging characteristics were recorded during visits at baseline, 6, 12, 18 and 24 months. RESULTS: Sixteen eyes of 16 patients were included (mean age 53±11 years; 14 men, 2 women). Mean duration of SRF before treatment initiation was 11.2±19.7 months. MRa treatment was administered during 21.0±5.1 months (range, 10-24 months). There was a progressive improvement of visual acuity (p=0.05), a decrease of foveal SRF height (p=0.011), central macular thickness (p=0.004) and subfoveal choroidal thickness (p=0.002) over 24 months. Changes in SRF were correlated with subfoveal choroidal thickness at 24 months (p=0.006, Spearman r=065). The mean time to complete foveal SRF resolution was 10.5±8.0 months after treatment initiation. At 24 months, foveal SRF resolution was achieved in 13 eyes (81%). Minor side effects occurred in five patients (31%) and resolved after switching between MRa. CONCLUSION: The visual and anatomical benefit of MRa treatment prolonged for 6 months or more in chronic, non-resolving CSC appeared to be maintained over a 24-month period. These results suggest that MRa can be proposed as an alternative therapy in severe CSC with advanced RPE alterations.


Assuntos
Coriorretinopatia Serosa Central/tratamento farmacológico , Espironolactona/administração & dosagem , Acuidade Visual , Administração Oral , Adulto , Idoso , Coriorretinopatia Serosa Central/diagnóstico , Corioide/patologia , Doença Crônica , Feminino , Angiofluoresceinografia , Seguimentos , Fundo de Olho , Humanos , Masculino , Pessoa de Meia-Idade , Antagonistas de Receptores de Mineralocorticoides/administração & dosagem , Retina/patologia , Estudos Retrospectivos , Fatores de Tempo , Tomografia de Coerência Óptica/métodos , Resultado do Tratamento
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