Search

Aims: Although diabetes mellitus (DM) is a common co-morbidity in chronic heart failure (HF) patients, European data on concurrent HF and DM treatment are lacking. Therefore, we have studied the HF treatment of patients with and without DM. Additionally, with the recent breakthrough of sodium–glucose cotransporter 2 (SGLT2) inhibitors in the field of HF, we studied the potential impact of this new drug in a large cohort of HF patients. Methods and results: A total of 7488 patients with chronic HF with a left ventricular ejection fraction 2, P Conclusions: In this large real-world HF registry, a high prevalence of DM was observed and diabetics more often received guideline-recommended target doses. Based on current evidence, the majority of patients would fulfil the enrichment criteria of SGLT2 trials in HF and the impact of this new drug class will be large.

BACKGROUND Mineralocorticoid receptor antagonist (MRA) when combined with either angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) may provide additional benefits of cardiovascular and kidney disease risk reduction in patients with diabetic kidney disease (DKD) and hypertension. We evaluated the effectiveness of combination therapy (MRAs, either spironolactone or eplerenone, plus ACEI/ARB) compared with monotherapy (ACEI/ARB only) in patients with DKD and hypertension. METHODS Retrospective cohort study was performed in patients (age ≥ 18 years) with hypertension, diabetes, and albuminuria between 2008 and 2018 within an integrated health system. MRA with ACEI/ARB compared to ACEI/ARB alone was evaluated on composite of cardiovascular events, progression to end-stage kidney disease, or all-cause mortality. Hyperkalemia was compared as a safety outcome. RESULTS We identified 1282 patients who received MRAs with ACEI/ARBs and 5484 patients who received ACEI/ARBs alone. Median exposure time for combination therapy was 126 days. The rates per 100 person-years of cardiovascular, kidney, or all-cause mortality outcomes were 12.2 and 9.2 for combination therapy and monotherapy, respectively (hazard ratios = 1.24, 95% Confidence Interval (CI):0.94, 1.63). Patients receiving combination therapy had greater reduction in urine albumin-to-creatinine ratio compared with monotherapy (Mean reduction: 823 and 585 mg/g; p

Purpose: To study structural and functional outcomes of cystoid macular degeneration (CMD) in chronic central serous chorioretinopathy (CSCR). Methods: This retrospective study included 26 eyes having chronic CSCR with CMD who underwent either observation, photodynamic therapy (PDT), micropulse laser, or eplerenone therapy. Various optical coherence tomography parameters were analyzed at baseline and 1 year. Results: Number of eyes that maintained or gained vision after treatment was 63.1%, compared to a loss of 2.1 ± 1.1 lines in observation group. Sub-foveal large choroidal vessel responded to PDT ( p = 0.03); while CMT ( p = 0.035) and intra-retinal cystoid spaces (0.037) responded to eplerenone. Longer duration of the symptoms and round cystoid spaces were associated with a decrease in CMT ( p = 0.03) and decrease in cystoid spaces size ( p = 0.02) respectively on follow up. Conclusion: Treatment of eyes with CMD prevents further deterioration of vision. Round configuration of intra-retinal cystoid space has a better anatomical outcome.

Стаття присвячена перспективам застосування еплеренону — селективного блокатора альдостеронових рецепторів — для лікування пацієнтів з різним ступенем артеріальної гіпертензії. Зростаючий обсяг клінічних досліджень свідчить, що різноспрямовані ефекти еплеренону — антигіпертензивний, вазо-, рено- і кардіопротекторний, антитромботичний — дозволяють домогтися ефективного зниження артеріального тиску, в тому числі й у пацієнтів з резистентною артеріальною гіпертензією, запобігти розвитку і прогресуванню органних уражень, знизити ризик загальної і серцево-судинної смертності, поліпшити якість життя і збільшити його тривалість у пацієнтів з АГ.

Background. Acute myocardial infarction (AMI) remains the leading cause of mortality in Ukraine and worldwide. The purpose of research was to analyze the influence of eplerenone on the disease course in patients with AMI complicated by the development of acute left ventricular insufficiency (ALVI) with preserved left ventricular ejection fraction. Materials and methods. 137 patients with ST elevation AMI complicated by ALVI were examined and divided into two groups. Group 1 — 65 patients who received eplerenone, group 2 — 72 patients who did not take aldosterone antagonists. All patients received standard treatment, 87 of them — thrombolytic therapy. We have evaluated clinical manifestations of heart failure, the results of echocardio­graphy, and the concentration of the N-terminal pro-B-type natriuretic peptide (NT-proBNP). Results. A regression of clinical symptoms of the heart failure was proved. It correla-ted with the positive dynamics of NT-proBNP and the size of the heart chambers when using medicine as a part of integrated therapy for AMI. In addition, during prolonged systema-tic eplerenone use, a proven positive dynamics of prognostic markers of the post-infarction period was noted in patients under examination. Conclusions. The use of eplerenone leads to inhibition of left ventricular remodeling in patients suffered AMI, contributes to the control of fluid volume, which leads to decrease and gradual regression of heart failure manifestations, even after ALVI.

Purpose. To report the occurrence of acute, bilateral, central serous chorioretinopathy (CSC), and pachychoroid spectrum disorder findings in patients with coronavirus disease 2019 (COVID-19). Methods. In recovered cases of COVID-19 with visual disturbances, complete ocular examinations with multimodal retinal and choroidal evaluation, including enhanced depth imaging optical coherence tomography, fluorescein or indocyanine green angiography, and blue autofluorescence, were obtained. Results. Four COVID-19 recovered patients presented with bilateral blurred vision. Ocular examination and imaging revealed pachychoroid and pachyvessels associated with choroidal hyperpermeability without any obvious intraocular inflammation. Bilateral localized serous retinal detachment was obvious in three cases compatible with pachychoroid associated with CSC manifestation and pachychoroid pigment epitheliopathy in one patient. CSC was resolved with treatment by steroidal antimineralocorticoid (Eplerenone) in two patients and by photodynamic therapy in one patient. None of the patients reported emotional stress and history of corticosteroid consumption. Conclusion. Hyperpermeability of the choroid, pachychoroidopathy, or choroidal vessel congestion can be observed or exacerbated in association with COVID-19.

The overactivation of the mineralocorticoid receptor (MR) in animal models of chronic kidney disease (CKD) increases sodium retention and hypertension and provokes inflammation and fibrosis in the kidneys, blood vessels, and the heart; these processes play an important role in the progression of cardiorenal disease. Accordingly, blockade of the MR is an attractive therapeutic intervention to retard the progression of CKD and improve cardiovascular morbidity and mortality. Finerenone is a novel, nonsteroidal MR antagonist (MRA) with a unique mode of action that is distinct from currently available steroidal MRAs. In animal models of CKD, finerenone has a more favorable benefit/risk ratio as compared with the steroidal MRAs such as spironolactone and eplerenone. In patients with type 2 diabetes and heart and/or kidney disease, phase II trials have revealed that compared with spironolactone, eplerenone, or placebo, finerenone displays benefits that exceed the risks of MR antagonism. In patients with CKD and type 2 diabetes, a large phase III trial has shown that, compared with placebo, finerenone improved kidney failure and cardiovascular outcomes. In the first part of this article, we explore the safety and efficacy of spironolactone and eplerenone in early- and late-stage CKD. In the second part, we describe the mechanism of action of finerenone and discuss the promising role of this nonsteroidal MRA as a novel therapeutic opportunity to improve clinical outcomes in patients with CKD.

Objectives This study investigated the impact of the MR antagonist (MRA) eplerenone on LVM in type 2 diabetes patients at high risk for cardiovascular disease (CVD). Background MRA activat...

Background Loop diuretics are the mainstay of congestion treatment in patients with heart failure (HF). We assessed the association between baseline loop diuretic use and outcome. We also compared the increment in risk related to diuretic dose with conventional prognostic enrichment criteria used in the EMPHASIS-HF trial, which included patients with systolic HF and mild symptoms, such as prior hospitalization and elevated natriuretic peptides. Methods Individual analyses were performed according to baseline loop diuretic usage (furosemide-equivalent dose > 40 mg, 1-40 mg, and no furosemide), and according to enrichment criteria adopted in the trial [i.e. recent hospitalization (< 30 days or 30 to 180 days prior to randomization) due to HF or other cardiovascular cause, or elevated natriuretic peptides]. The primary endpoint was a composite of cardiovascular death or HF hospitalization. Results Loop diuretic usage at baseline (HR for > 40 mg furosemide-equivalent dose = 3.16, 95% CI 2.43-4.11; HR for 1-40 mg = 2.06, 95% CI 1.60-2.65) was significantly associated with a higher risk for the primary endpoint in a stepwise manner when compared to no baseline loop diuretic usage. In contrast, the differences in outcome rates were more modest when using history of hospitalization and/or BNP: all HR ranged from 1 (reference, non-HF related CV hospitalization > 30 days) to 2.04 (HF hospitalization < 30 days). The effect of eplerenone on the primary endpoint was consistent across subgroups in both analyses (P for interaction >= 0.2 for all). Conclusions Loop diuretic usage (especially at doses > 40 mg) identified patients at higher risk than history of HF hospitalization and/or high BNP blood concentrations. Graphic abstract

The activation of the renin-angiotensin-aldosterone system prevents the uptake of norepinephrine and promotes structural remodeling of the heart. The mineralocorticoid receptor antagonist (MRA) eplerenone prevents left ventricular (LV) remodeling in patients with acute myocardial infarction, but its influence on cardiac sympathetic nerve activity (CSNA) has not been determined. We retrospectively evaluated the first ST-segment elevation myocardial infarction (STEMI) patients in our database who underwent 123I-metaiodobenzylguanidine (MIBG) scintigraphy 3 weeks after admission. Eighty-four STEMI patients after primary coronary angioplasty were selected, and used propensity score matching to compare patients who treated with MRA (N = 42), and those who did not (N = 42). The LV end-diastolic volume, end-systolic volume, and ejection fraction were determined by echocardiography, and plasma procollagen type III amino terminal peptide (PIIINP) was measured before and 3 weeks after treatment. The delayed total defect score (TDS), delayed heart/mediastinum count (H/M) ratio, and washout rate (WR) were determined using 123I-MIBG scintigraphy after 3 weeks. Following primary angioplasty, age, gender, risk factors, culprit coronary artery, peak serum creatine phosphokinase concentration, and recanalization time were similar in the two groups. However, the MRA group showed significantly lower TDS and WR values (TDS: 22.8 ± 8.1 vs 32.2 ± 11.5, P < 0.005; WR: 31.1 ± 9.0% vs 42.7 ± 9.9%, P < 0.001) and a significantly higher H/M ratio (2.23 ± 0.41 vs 2.03 ± 0.36, P < 0.05) than the non-MRA group. The degree of change in LV parameters, and PIIINP were more favorable in the MRA group than in the non-MRA group. Moreover, multiple linear regression analyses revealed that both WR and not MRA treatment were significant predictor for LV remodeling, along with PIIINP concentrations. Administration of eplerenone improves CSNA and prevents LV remodeling in patients with a first STEMI.

Aim. To study the effect of eplerenone on the activity of free radical oxidation and renal function in rats with experimental diabetes mellitus induced by streptozotocin. Materials and methods . Experiments were carried out on 36 male Wistar rats. Diabetes mellitus (DM) was simulated by a single intraperitoneal injection of streptozotocin at a dose of 65 mg/kg. Eplerenone was injected into the stomach at a dose of 50 mg/kg. Results. It was found that eplerenone in experimental diabetic nephropathy (DN) significantly attenuated proteinuria: the concentration of protein in the urine became 4 times lower than in untreated DN ( p < 0.001). In the kidneys, eplerenone therapy normalized the structure and function of renal glomeruli and restored the podocyte number, which was reduced by 37.8% in the DN model. Free radical oxidation (FRO) in the kidneys of rats treated with eplerenone increased – the concentration of thiobarbituric acid reactive substances rose by 1.5 times ( p = 0.009), and changes in the activity of antioxidant enzymes, such as superoxide dismutase (a decrease by 2.4 times, p = 0.002), catalase (an increase by 1.8 times, р < 0,001), and glutathione peroxidase (an increase by 1.5 times, р < 0.001) were observed, as opposed to the values in the controls. Conclusion. In streptozotocin-induced experimental diabetic nephropathy in rats, eplerenone had a nephroprotective effect, but increased oxidative stress in the kidneys. The increase in FRO could be determined by the nongenomic effect of aldosterone, which accumulates under conditions of prolonged mineralocorticoid receptor (MR) blockade. The nephroprotective effect of eplerenone can be associated with the weakening of the genomic effects of aldosterone, realized with the participation of MR.

Treatment of chronic heart failure (CHF) is very controversial. The issue of optimal doses of beta-blockers, ACE inhibitors, aldosterone receptor antagonists, statins in patients with CHF has not been conclusively addressed. Achieving the maximum tolerated doses of drugs, though related to reduced mortality, but is accompanied by an increase in adverse drug reactions. The aim. To present and discuss our own clinical and scientific data concerning the role of beta-blockers and inhibitors of the renin-angiotensin aldosterone system, diuretics, statins in the treatment of CHF patients and optimization of dosage schemes. Material and methods. The study included 88 patients with CHF of ischemic origin, with sinus rhythm, stage II AB, NYHA FC II–IV, 58 – with reduced LV EF (HFrEF) and 30 – with preserved LV EF (HFpEF). The mean age of patients was 69.18 ± 9.97 years, men 52 % (n = 46). The median follow-up of the CHF patients was 396 days, the maximum number of follow-up days was 1302. During the observation period, 14 endpoints were registered, which accounted for 15.91 % of events: 7 deaths (8.0 %), 2 strokes (2.3 %), 2 cases of acute coronary syndrome (2.3 %), 3 progressive heart failure cases (3.4 %). Kaplan–Mayer curves were drawn to assess survival rate, and the significance of difference between groups was calculated by the criteria of Gehan–Wilcoxon, Cox–Mantel and log-rank test. Risk factors were determined, and prognostic uni- and multi-variant Cox proportional hazards regression models were used. The cut-off values of quantitative risk factors were obtained by ROC analysis. Results. The increase in the relative risk of adverse cardiovascular events in the CHF patients regardless of LV EF was associated with a daily carvedilol dose of more than 25 mg (HR = 1.05; 95 % CI 1.009–1.093; P = 0.0171); eplerenone – more than 12.5 mg (HR = 1.073; 95 % CI 1.005–1.144; P = 0.034), torasemide – more than 5 mg (HR = 1.13; 95 % CI 1.021–1.255; P = 0.019); rosuvastatin – more than 10 mg (HR = 1.107; 95 % CI 1.007–1.203; P = 0.035), and the trend in using atorvastatin at a dose of less than 10 mg (HR = 1.05; 95 % CI 0.951–1.165; P = 0.327). The use of ramipril in a daily dose of less than 2.5 mg was accompanied by a trend towards the 22 % reduced relative risk of adverse cardiovascular events (HR = 0.78; 95 % CI 0.384–1.580; P = 0.491). Conclusions. Positive treatment outcomes in the CHF patients, regardless of the phenotype, were associated with low daily doses of ramipril (10.0 mg).

Diabetic nephropathy (DN) is the leading cause of chronic kidney disease. Even though mineralocorticoid receptor antagonists (MRA) induce incremental reductions in urine albumin excretion when added to angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, this combination is infrequently used because of an increased risk of hyperkalemia. In this context, finerenone, a novel selective MRA that appears to be associated with lower risk for hyperkalemia compared with other MRAs (spironolactone and eplerenone), might represent a useful tool in patients with DN. A recent large randomized trial suggested that finerenone delays the progression of DN and might also reduce cardiovascular morbidity in patients with DN. However, more data are needed to clarify the safety and efficacy of finerenone in this high-risk population.

There are many experimental data supporting the involvement of aldosterone and mineralcorticoid receptor (MR) activation in the genesis and progression of chronic kidney disease (CKD) and cardiovascular damage.Many studies have shown that in diabetic and non-diabetic CKD, blocking the renin-angiotensin-aldosterone (RAAS) system with conversion enzyme inhibitors (ACEi) or angiotensin II receptor blockers (ARBs) decreases proteinuria, progression of CKD and mortality, but there is still a significant residual risk of developing these events.In subjects treated with ACEi or ARBs there may be an aldosterone breakthrough whose prevalence in subjects with CKD can reach 50%. Several studies have shown that in CKD, the aldosterone antagonists (spironolactone, eplerenone) added to ACEi or ARBs, reduce proteinuria, but increase the risk of hyperkalemia. Other studies in subjects treated with dialysis suggest a possible beneficial effect of antialdosteronic drugs on CV events and mortality. Newer potassium binders drugs can prevent/decrease hyperkalemia induced by RAAS blockade, and may reduce the high discontinuation rates or dose reduction of RAAS-blockers.The nonsteroidal MR blockers, with more potency and selectivity than the classic ones, reduce proteinuria and have a lower risk of hyperkalemia. Several clinical trials, currently underway, will determine the effect of classic MR blockers on CV events and mortality in subjects with stage 3b CKD and in dialysis patients, and whether in patients with type 2 diabetes mellitus and CKD, optimally treated and with high risk of CV and kidney events, the addition of finerenone to their treatment produces cardiorenal benefits.Large randomized trials have shown that sodium glucose type 2 cotransporter inhibitors (SGLT2i) reduce mortality and the development and progression of diabetic and nondiabetic CKD. There are pathophysiological arguments, which raise the possibility that the triple combination ACEi or ARBs, SGLT2i and aldosterone antagonist provide additional renal and cardiovascular protection. Resumen: Hay abundantes datos experimentales que sustentan la participación de la aldosterona y la estimulación del receptor mineralcorticoide (RM) en la génesis y progresión de la enfermedad renal crónica (ERC) y en el daño cardiovascular.Muchos estudios han demostrado que en la ERC diabética y no diabética, el bloqueo del sistema renina angiotensina-aldosterona (SRAA) con inhibidores de enzima de conversión (iECA) ó antagonistas del receptor de angiotensina II (ARA2) disminuye la proteinuria, la progresión de la ERC y la mortalidad, pero persiste todavía importante riesgo residual de desarrollo de estos eventos.En sujetos tratados con iECA ó ARA2 puede haber un escape de la aldosterona cuya prevalencia en sujetos con ERC puede alcanzar el 50 %. Diversos estudios han demostrado que, en la ERC, los fármacos antialdosterónicos clásicos (espironolactona, eplerenona) añadidos a iECA ó ARA2, reducen la proteinuria, pero aumentan el riesgo de hiperkaliemia. Otros estudios en sujetos tratados con diálisis sugieren un posible efecto beneficioso de los antialadosterónicos sobre eventos CV y mortalidad. Los nuevos ligadores intestinales de K+ pueden prevenir ó reducir la hiperkaliemia inducida por el bloqueo del SRAA, y disminuir la desprescripción o la reducción de dosis de fármacos bloqueantes del SRAA.Los bloqueantes del RM no esteroideos, con más potencia y selectividad que los clásicos, reducen la proteinuria y tienen menos riesgo de hiperkaliemia. Varios ensayos clínicos, actualmente en realización, determinarán el efecto de los bloqueantes clásicos del RM sobre eventos CV y mortalidad en sujetos con ERC estadio 3b y en enfermos en diálisis, y si en enfermos con diabetes mellitus tipo 2 y ERC, óptimamente tratados y con elevado riesgo de eventos CV y renales, la adición de finerenona a su tratamiento produce beneficios cardiorrenales.Los inhibidores del cotransportador sodio-glucosa tipo 2 (iSGLT2) han demos-trado reducir la mortalidad y el desarrollo y progresión de la nefropatía diabética y no diabética. Hay argumentos fisiopatológicos, que suscitan la posibilidad de que la triple combinación, iECA ó ARA2, iSGLT2 y antagonista de aldosterona ofrezca mayor protección renal y vascular.

Central serous chorioretinopathy (CSC) is one of the main causes of impaired visual acuity in patients younger than 60 years. Its pathophysiology remains partially unknown, although it has been postulated that choroidal hyper-permeability may be involved. This typically produces a neurosensory retinal detachment and/or a detachment of the retinal pigment epithelium in the posterior pole. Although acute CSC generally does not require treatment, when chronic it must be treated to avoid visual impairment. With the development of new imaging techniques, there has been an improvement in diagnosis, and different therapeutic strategies have been proposed. Various treatments for the management of chronic CSC have currently been shown to be useful to improve or stabilise visual acuity, the resolution of subretinal fluid, and to prevent recurrences. The most commonly used treatments today are photodynamic therapy, micropulse subthreshold laser, mineralocorticoid antagonists, or anti-vascular endothelial growth factor drugs. There are also other proposals and new treatments being developed, with promising results. This review aims to provide the reader with an overview of the current scientific evidence of the different treatment options available for CSC in order to help decision-making in clinical practice.

OBJECTIVES In human studies and genetically altered mouse studies, variants in the striatin gene (STRN) are associated with increased blood pressure (BP) and aldosterone on a liberal salt diet. This clinical trial is based on the presumed mechanism for striatin-associated HTN - increased aldosterone. It is designed to determine if participants with the STRN risk alleles will have a greater BP reduction on a liberal salt diet with a specific, mechanism-based therapy - a mineralocorticoid receptor antagonist, eplerenone - as compared with a nonspecific anti-hypertensive therapy - amlodipine. METHODS One hundred five hypertensive adults with the STRN risk alleles (SNP rs2540923 carriers or rs888083 homozygotes) will be enrolled in a 12-week, double-blind, dose-escalation, clinical trial. After a minimum 2-week washout period and baseline assessment of BP on a liberal salt diet, participants will be randomized to either daily eplerenone or amlodipine. Participants will take daily at-home BP recordings as a safety check. After 4 and 8 weeks of drug therapy, BP will be measured by the study team and medication will be increased, if needed, to achieve a participant goal BP of

A higher incidence of bilateral primary aldosteronism in women is reported. Treatment of bilateral primary aldosteronism usually involves mineralocorticoid receptor antagonists. However, the impact of sex on renal outcomes is unknown. We compared renal outcomes between the sexes after mineralocorticoid receptor antagonist initiation by analyzing data obtained from 415 female and 313 male patients with bilateral primary aldosteronism who were treated with spironolactone or eplerenone in the JPAS (Japan Primary Aldosteronism Study). Over the course of 5 years, the temporal reduction in the estimated glomerular filtration rate was greater in women than in men ( P 2 per year versus −1.04 mL/min per 1.73 m 2 per year, P

Background In chronic central serous chorioretinopathy, fluid accumulates in the subretinal space and causes permanent vision loss in ≈ 30% of patients. There is no definitive treatment. Previous research suggests that the mineralocorticoid receptor antagonist eplerenone is effective but it is not licensed for chronic central serous chorioretinopathy. Objectives The objective was to evaluate whether or not eplerenone was safe and superior to placebo for treating chronic central serous chorioretinopathy. We also aimed to set up a biobank of DNA, serum and plasma samples from treatment-naive participants for future research. Design The trial was a parallel, randomised (1 : 1 ratio), multicentre, double-masked, placebo-controlled superiority trial comparing eplerenone plus usual care with placebo plus usual care. Participants were randomly allocated to eplerenone or placebo using a secure online system that returned a unique number corresponding to a bottle of the investigational medicinal product. Participants, clinical care teams, pharmacists, outcome assessors and the trial management group were masked. Setting The trial took place in 22 NHS hospitals in the UK. Participants Eligible participants were patients aged 18–60 years with treatment-naive chronic central serous chorioretinopathy of at least 4 months’ duration, a best corrected visual acuity score of 54–85 letters and no other conditions affecting visual acuity or contraindications to taking eplerenone or placebo. Interventions The intervention was oral eplerenone (25 mg/day for 1 week, increased to 50 mg/day for up to 12 months). Placebo was a lactose-filled capsule that appeared identical to the overencapsulated eplerenone tablets. To maintain blinding, participants in the placebo group followed the same dose escalation schedule as the eplerenone group. Usual care was included in both groups and was administered at the discretion of clinicians. Main outcome measures The primary outcome was best corrected visual acuity score at 12 months. Secondary outcomes were low-luminance visual acuity, central subfield retinal thickness, change in subretinal fluid thickness, systemic and ocular adverse events, macular atrophy of the retinal pigment epithelium, subfoveal choroidal thickness, choroidal permeability, resolution of subretinal fluid, time to recurrence of subretinal fluid, fundus fluorescein angiography phenotype, incidence of chronic central serous chorioretinopathy in the fellow eye, and patient-reported visual function. Results Between 11 January 2017 and 22 February 2018, 57 participants were randomised to eplerenone and 57 to placebo; 57 and 54 participants, respectively, were included in the analysis of the primary outcome. The modelled mean best corrected visual acuity score at 12 months in the eplerenone and placebo groups was 80.4 letters (standard deviation 4.6 letters) and 79.5 letters (standard deviation 4.5 letters), with an estimated difference between groups of 1.73 letters (95% confidence interval –1.12 to 4.57 letters; p = 0.24). Hyperkalaemia occurred in eight participants in each group (14%). No serious adverse events occurred in the eplerenone group; three unrelated serious adverse events occurred in the placebo group. Limitations Limitations included the inability to prevent co-treatments and discontinuation of the investigational medicinal product in the event of resolution or hyperkalaemia. Conclusions Eplerenone was safe but not superior to placebo in improving best corrected visual acuity in people with chronic central serous chorioretinopathy during 12 months of follow-up. In future work, ophthalmologists should investigate alternative treatments for this condition, which remains complicated to treat. Trial registration Current Controlled Trials ISRCTN92746680. Funding This project was funded by the Efficacy and Mechanism Evaluation (EME) Programme, a MRC and National Institute for Health Research (NIHR) partnership. This will be published in full in Efficacy and Mechanism Evaluation; Vol. 8, No. 2. See the NIHR Journals Library website for further project information.

Background: Although diuretics are one of the most widely used drugs by nephrologists, their antiproteinuric properties are not generally taken into consideration. Summary: Thiazide diuretics have been shown to reduce proteinuria by >35% in several prospective controlled studies, and these values are markedly increased when combined with a low-salt diet. Thiazide-like diuretics (indapamide and chlorthalidone) have shown similar effectiveness. The antiproteinuric effect of mineralocorticoid receptor antagonists (spironolactone, eplerenone, and finerenone) has been clearly established through prospective and controlled studies, and treatment with finerenone reduces the risk of chronic kidney disease progression in type-2 diabetic patients. The efficacy of other diuretics such as amiloride, triamterene, acetazolamide, or loop diuretics has been less explored, but different investigations suggest that they might share the same antiproteinuric properties of other diuretics that should be evaluated through controlled studies. Although the inclusion of sodium-glucose cotransporter-2 inhibitors (SGLT2i) among diuretics is a controversial issue, their renoprotective and cardioprotective properties, confirmed in various landmark trials, constitute a true revolution in the treatment of patients with kidney disease. Recent subanalyses of these trials have shown that the early antiproteinuric effect induced by SGLT2i predicts long-term preservation of kidney function. Key Message: Whether the early reduction in proteinuria induced by diuretics other than finerenone and SGLT2i, as summarized in this review, also translates into long-term renoprotection requires further prospective and observational studies. In any case, it is important for the clinician to be aware of the antiproteinuric properties of drugs so often used in daily clinical practice.

OBJECTIVE The aim: To increase the treatment effectiveness of CHF patients after MI with stenting by using magnesium and potassium salts of gluconic acid, eplerenone, and rivaroxaban in complex therapy. PATIENTS AND METHODS Materials and methods: The research was performed at the premises of Ivano-Frankivsk Regional Clinical Cardiology Centre, Ukraine. 84 patients with CHF after past MI were examined. RESULTS Results and conclusions: A more pronounced anti-ischemic effect has been linked to the use of combination therapy with rivaroxaban on the background of basic therapy (BT) in patients with CHF after MI, compared with the use of magnesium and potassium salts of gluconic acid or eplerenone. The use of eplerenone in the complex treatment of these patients on the background of BT has been proven to provide a pronounced reverse remodeling of the left myocardium in the postinfarction period.

The exploratory analysis of FOURIER trial has offered a ray of hope for patients with nonrheumatic aortic stenosis (AS). At present, the only definitive treatment of severe AS is aortic valve replacement (AVR). Despite transaortic valvular replacement revolutionizing the treatment of AS, it still remains a progressive condition, with no disease-modifying pharmacotherapy. Angiotensin-converting-enzyme inhibitors, angiotensin receptor blockers, eplerenone, nitrates and statins all have been tried previously but failed to slow down the progression of aortic stenosis. Recently, there has been an emerging role of lipoprotein A [Lp(a)] in the pathogenesis of AS. This raises the possibility that long-term therapy with specific emphasis on Lp(a) reduction may reduce or slow the progression of AS.

Sodium changes are common in myocardial infarction (MI) complicated with left ventricular systolic dysfunction (LVSD) and/or heart failure (HF). Sodium handling is fine-tuned in the distal nephron, were eplerenone exhibits some of its pleotropic effects. Little is known about the effect of eplerenone on serum sodium and the prognostic relevance of sodium alterations in patients with MI complicated with LVSD and/or HF.The EPHESUS trial randomized 6632 patients to either eplerenone or placebo. Hyponatremia and hypernatremia were defined as sodium 135 mmol/L or 145 mmol/L, respectively. Linear mixed models and time updated Cox regression analysis were used to determine the effect of eplerenone on sodium changes and the prognostic importance of sodium changes, respectively. The primary outcomes were all-cause mortality and a composite of cardiovascular (CV) mortality and CV-hospitalization.A total of 6221 patients had a post-baseline sodium measurement, 797 patients developed hyponatremia (mean of 0.2 events/per patient) and 1476 developed hypernatremia (mean of 0.4 events/per patient). Patients assigned to eplerenone had a lower mean serum sodium over the follow-up (140 vs 141 mmol/L; p 0.0001) and more often developed hyponatremia episodes (15 vs 11% p = 0.0001) and less often hypernatremia episodes (22 vs. 26% p = 0.0003). Hyponatremia, but not hypernatremia was associated with adverse outcome for all outcome endpoints in the placebo group but not in the eplerenone group (interaction p value 0.05 for all). Baseline sodium values did not influence the treatment effect of eplerenone in reducing the various endpoints (interaction p value 0.05 for all). Development of new-onset hyponatremia following eplerenone initiation did not diminish the beneficial eplerenone treatment effect.Eplerenone induces minor reductions in serum sodium. The beneficial effect of eplerenone was maintained regardless of the baseline serum sodium or the development of hyponatremia. Sodium alterations should not refrain clinicians from prescribing eplerenone to patients who had an MI complicated with LVSD and/or HF.ClinicalTrials.gov identifier: NCT00232180. Serum sodium and eplerenone use in patients with a myocardial infarction and left ventricular dysfunction or heart failure: insights from the EPHESUS trial.

Aim. To study the three-year dynamics of left ventricular (LV) structural parameters with the four-component antihypertensive therapy in patients with resistant arterial hypertension (RAH). Material and methods. A total of 102 patients with true RAH were included. The duration of the treatment was 3.2 ± 0.1 years. Patients received triple single-pill combination of antihypertensive drugs (TSPC), which was alternately added by spironolactone, eplerenone, moxonidine, torasemide, or nebivolol for three-months treatment. Than patients received the TSPC with an addition of the most effective of the four medications listed. Office and ambulatory blood pressure (BP) measurements and echocardiography were performed, clinical characteristics; specifics of neurohumoral and proinflammatory status were assessed. Results. The patients were divided into 2 groups according to the changes in LV mass index (LVMI) within three years. The 1 st group included 68 patients who demonstrated regression of LV hypertrophy (LVH). The 2 nd group included 28 patients who had LVMI unchanged or increased. LVMI was normalized in 38.2 % of patients, and a degree of LVH was reduced from severe to moderate in 61.8 % of patients in achieving the target BP level in 44 % of patients and restoring the physiological 24-hour BP rhythm in 39 % of patients. In the 2 nd group, 28.6 % of patients achieved BP targets; a large proportion of them were patients with concomitant coronary heart disease (42.3 %) and chronic kidney disease (64.3 %). Conclusions. Effective antihypertensive therapy providing 24-hour BP control and restoring the physiological 24-hour BP rhythm contributes to LVH regression in 66.7 % of patients with RAH. Higher baseline LVMI (β = 0.655; P < 0.0001) and plasma active renin (β = 0.442; P = 0.005), lower 24-hour urinary albumin excretion rate (β = -0.475; P < 0.0001) are independent predictors of LVH regression in RAH patients.

This paper attempts to explain how the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus causes the complications that make coronavirus disease 2019 (COVID-19) a serious disease in specific patient subgroups. It suggests that cortisol-associated activation of the mineralocorticoid receptor (MR) in epithelial and endothelial cells infected with the virus stimulates the release of adenosine 5′-triphosphate (ATP), which then acts back on purinergic receptors. In the lung this could produce the nonproductive cough via purinergic P2X3 receptors on vagal afferent nerves. In endothelial cells it could stimulate exocytosis of Weibel-Palade bodies (WPBs) that contain angiopoietin-2, which is important in the pathogenesis of acute respiratory distress syndrome (ARDS) by increasing capillary permeability and von Willebrand factor (VWF), which mediates platelet adhesion to the endothelium and hence clotting. Angiopoietin-2 and VWF levels both are markedly elevated in COVID-19–associated ARDS. This paper offers an explanation for the sex differences in SARS-CoV-2 complications and also for why these are strongly associated with age, race, diabetes, and body mass index. It also explains why individuals with blood group A have a higher risk of severe infection than those with blood group O. Dexamethasone has been shown to be of benefit in coronavirus ARDS patients and has been thought to act as an anti-inflammatory drug. This paper suggests that a major part of its effect may be due to suppression of cortisol secretion. There is an urgent need to trial the combination of dexamethasone and an MR antagonist such as spironolactone to more effectively block the MR and hence the exocytosis of WPBs.

BACKGROUND Nocturnal hypertension is an important phenotype of abnormal diurnal blood pressure (BP) variability and a known risk marker for target organ damage and cardiovascular events. This study aimed to assess the differential BP-lowering effects of esaxerenone vs. eplerenone on nocturnal BP in hypertensive patients with different nocturnal dipping patterns. METHODS This was a post hoc analysis of the “Esaxerenone (CS-3150) Compared to Eplerenone in Patients with Essential Hypertension” study (NCT02890173), which was a phase 3, multicenter, randomized, controlled, double-blind, parallel-group clinical study conducted in Japan. Ambulatory BP monitoring data were collected. RESULTS Patients (n = 1,001) were randomized to esaxerenone 2.5 mg/day (n = 331) or 5 mg/day (n = 338), or eplerenone 50 mg/day (n = 332). Reductions in nighttime systolic BP (95% confidence interval) were significantly greater with 2.5 and 5 mg/day esaxerenone vs. eplerenone (−2.6 [−5.0, −0.2] and −6.4 mm Hg [−8.8, −4.0], respectively). Esaxerenone significantly reduced nighttime BP from baseline compared with eplerenone in non-dippers with previously uncontrolled BP. In addition, esaxerenone did not markedly alter nighttime BP in extreme dipper patients. In the esaxerenone 5 mg/day group, esaxerenone-induced decreases in nighttime BP were greater than eplerenone-induced decreases in older patients. CONCLUSIONS Esaxerenone may be an effective treatment option for nocturnal hypertension, especially in older patients and those with a non-dipper pattern of nocturnal BP., Graphical Abstract Graphical Abstract

Conventionally, rennin–angiotensin–aldosterone system (RAAS) inhibition has focused on angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers and angiotensin receptor-neprilysin inhibitors (ARNI) are the latest addition to this armamentarium. However, mineralocorticoid receptor antagonists (MRAs) also constitute an integral part of this anti-RAAS brigade, which are perceived more often as diuretics and are often under prescribed in heart failure (HF) despite being universally advocated by all major guidelines. Apart from HF, they have also shown promise in the management of hypertension, post-myocardial infarction, and hyperaldosteronism. Eplerenone, Food and Drug Administration (FDA) approved in 2002, is an acceptable alternative to spironolactone due to its sparing androgenic effects. In two big pivotal trials in heart failure (EMPHASIS -HF) and post-myocardial infarction (EPHESUS), the drug has firmly shown a reduction in adverse cardiovascular events. It has an established place in the management of resistant hypertension too. In this article, we will discuss the role of RAAS and its pathophysiology, pitfalls of spironolactone, which led to success of its congener, eplerenone, major studies conducted on eplerenone, current role of eplerenone, and comparison of the two MRAs.

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.

A clinical case of the development of classic Dressler syndrome in a young patient with acute diffuse myocarditis is described. Timely diagnosis, administration of glucocorticoid and long-term complex therapy using beta-blockers (carvedilol), mineralocorticoid receptor blockers (eplerenone) not only led to the disappearance of Dressler’s syndrome, but also to a fairly rapid recovery of the patient from the underlying disease.

Purpose: To compare the macular morphology of good and poor responders to eplerenone treatment in chronic central serous chorioretinopathy (CSCR) patients. Methods: 30 eyes of 29 patients with chronic CSCR were treated with 50 mg/day oral eplerenone and followed up for one year. The integrity of outer retinal layers at baseline was assessed using optical coherence tomography. Patients who showed complete resolution of subretinal fluid at one year were assigned to the good responder group (Group 1), whilst those who showed moderate or no resolution were classified as poor responders (Group 2). Results: Ellipsoid zone interruption, ELM interruption and hyperreflective foci in outer segment (OS) and outer nuclear layer (ONL) was significantly more frequent in Group 2 than in Group 1 (pConclusion: There is higher chance of the resolution of subretinal fluid after eplerenone treatment in CSCR patients with intact outer retinal layers at baseline. Baseline morphologic evaluation of the outer retinal layers on OCT scans can be useful in predicting the response to mineralocorticoid receptor antagonist therapy in these patients.

Purpose: To assess the morphological and functional outcome of oral eplerenone for treatment of patients with chronic central serous chorioretinopathy (CSC) in a real life experience. Patients and methods: In this retrospective study, we reviewed the clinical files of 30 patients with chronic CSC. All patients were treated with eplerenone for a period of 6 weeks or 3 months depending on the clinical response. Main outcome measures included: best corrected visual acuity (BCVA), central macular thickness (CMT) and height of the subretinal fluid (SRF). Comparisons between responders and non-responders were performed to identify factors that were predictive of the treatment response. Results: All patients were treated with eplerenone 18 ± 20 weeks after onset of the first symptoms. BCVA (LogMAR) improved from 0.2 ± 0.2 to 0.13 ± 0.18 at 6 weeks ( p = 0.01) and to 0.09 ± 0.15 at 3 months ( p = 0.01). Mean CMT decreased from 409 ± 136 to 323 ± 87 µm at 6 weeks ( p = 0.001) and to 298 ± 98 µm at 3 months ( p = 0.01). Mean height of SRF decreased from 153 ± 126 to 73 ± 79 µm at 6 weeks ( p = 0.001) and to 49 ± 88 µm at 3 months ( p = 0.005). Complete resolution of SRF was achieved in 20 patients after 3 months (67%). Reported stress in the medical history was the only statistical significant predictive factor associated with a positive treatment response. Conclusion: This study showed a statistically significant improvement of the best corrected visual acuity and a significant reduction of macular thickness and subretinal fluid in patients with chronic CSC treated with oral eplerenone, especially in patients under stress.

Neuromuscular cardiopulmonary medicine is entering a new and exciting phase, with studies that assess the respiratory effect of emerging genetic and molecular therapies. In this year's neuromuscular Year in Review, we focus on Duchenne muscular dystrophy (DMD), reviewing studies that evaluate the respiratory effect of eteplirsen, the cardiopulmonary effects of ataluren, and a study comparing the use of spironolactone with eplerenone for the treatment of DMD-related cardiomyopathy.

The steroidal mineralocorticoid receptor (MR) antagonists, spironolactone and eplerenone, decrease blood pressure, and attenuate the progression of chronic kidney disease (CKD). However, their use is limited by the fear of inducing hyperkalemia, gynecomastia, impotence, and amenorrhea. Esaxerenone is a novel nonsteroidal MR blocker (MRB) that has been recently developed. In vitro studies have revealed that esaxerenone has a high potency and selectivity for MR compared with spironolactone and eplerenone. Further studies have shown that esaxerenone elicits a strong blood pressure-lowering effect in hypertensive animals. Following the results from phase III clinical trials that esaxerenone is an effective and well-tolerated MRB in Japanese hypertensive patients, esaxerenone became clinically available in Japan from May 2019 for hypertensive patients. Thus, esaxerenone is a promising treatment option for patients with hypertension. In addition, both preclinical studies and phase II clinical trials have shown that esaxerenone elicits renoprotection independent of its antihypertensive effect. Recently, a phase III clinical trial (ESAX-DN study) has also demonstrated the safety and efficacy of esaxerenone in patients with type 2 diabetes and microalbuminuria. These data support future clinical development of esaxerenone for the treatment of renal disease.

The present study explored the role and mechanisms of mineralocorticoid receptor antagonists in β-amyloid (Aβ)-induced cognitive impairment. A single intracerebroventricular injection of Aβ1-42 was given to mice, and after 14 days of injection, memory was evaluated using the Morris water maze test. Spironolactone (25 and 50 mg/kg) and eplerenone (50 and 100 mg/kg) were administered for two days before and for 14 days after Aβ injection. Mineralocorticoid receptor blockers attenuated Aβ-induced cognitive impairment assessed in terms of decrease in day 4 escape latency time (ELT) in comparison to day 1 ELT (suggesting an increase in learning) along with an increase in time spent in target quadrant on day 5 (suggesting the retrieval of learned things). These drugs also increased the expression of BDNF, H2 S, Nrf2, reduced glutathione, and decreased β-amyloid and TNF-α in the frontal cortex and hippocampus. Co-administration of ANA-12, BDNF receptor antagonist (0.25 and 0.5 mg/kg) abolished cognitive improving functions of mineralocorticoid receptor blockers, attenuated H2 S, Nrf2, reduced glutathione, and decreased β-amyloid and TNF-α. It is concluded that spironolactone and eplerenone attenuate cognitive decline of Alzheimer's type, possibly through upregulation of BDNF levels in the frontal cortex and hippocampus, which may increase H2 S, decrease Aβ, activate Nrf2-dependent antioxidant system, and decrease neuroinflammation.

Aldosterone modulates the activity of both epithelial (specifically renal) and non-epithelial cells. Binding to the mineralocorticoid receptor (MR), activates two pathways: the classical genomic and the rapidly activated non-genomic that is substantially modulated by the level of striatin. We hypothesized that disruption of MR’s non-genomic pathway would alter aldosterone-induced cardiovascular/renal damage. To test this hypothesis, wild type (WT) and striatin heterozygous knockout (Strn+/−) littermate male mice were fed a liberal sodium (1.6% Na+) diet and randomized to either protocol one: 3 weeks of treatment with either vehicle or aldosterone plus/minus MR antagonists, eplerenone or esaxerenone or protocol two: 2 weeks of treatment with either vehicle or L-NAME/AngII plus/minus MR antagonists, spironolactone or esaxerenone. Compared to the WT mice, basally, the Strn+/− mice had greater (~26%) estimated renal glomeruli volume and reduced non-genomic second messenger signaling (pAkt/Akt ratio) in kidney tissue. In response to active treatment, the striatin-associated-cardiovascular/renal damage was limited to volume effects induced by aldosterone infusion: significantly increased blood pressure (BP) and albuminuria. In contrast, with aldosterone or L-NAME/AngII treatment, striatin deficiency did not modify aldosterone-mediated damage: in the heart and kidney, macrophage infiltration, and increases in aldosterone-induced biomarkers of injury. All changes were near-normalized following MR blockade with spironolactone or esaxerenone, except increased BP in the L-NAME/AngII model. In conclusion, the loss of striatin amplified aldosterone-induced damage suggesting that aldosterone’s non-genomic pathway is protective but only related to effects likely mediated via epithelial, but not non-epithelial cells.

Background Minoxidil solution has routinely been used for decades for the treatment of androgenic alopecia. Central serous chorioretinopathy (CSCR) is a rare side-effect noted following prolonged topical minoxidil therapy for androgenic alopecia. In this report, we describe a case of a 41-year-old young man who developed CSCR following prolonged therapy with topical Minoxidil solution and was treated with oral eplerenone. Case presentation A 41-year-old male presented to the retina clinic with complaints of seeing a black spot, blurred vision and metamorphopsia involving the right eye for the past 4 months. He was on treatment for androgenic alopecia with topical 5% Minoxidil application on scalp two times a day. He noticed the symptoms 8 months after starting the treatment and had stopped the medication since the past 2 months. On examination, best-corrected visual acuity was 20/20 in both eyes. Fundoscopic examination of the right eye with +78D lens on slit lamp revealed the presence of subretinal fluid and few focal spots of retinal pigment epithelial alterations. Optical coherence tomography scan evaluation showed the presence of subretinal fluid (SRF) and pachychoroid supporting the diagnosis of CSCR. Indocyanine green angiography revealed dilated hyperpermeable choroidal vasculature on the nasal side of the fovea in the early and later phases of the angiogram. The patient was diagnosed with CSCR as a possible consequence of the topical minoxidil solution. Patient was asked to avoid future use of Minoxidil and was started on oral eplerenone therapy 50 mg/day for 4 consecutive weeks. One month later, there was complete resolution of his symptoms and SRF. At the final follow-up visit, 2 months after starting the therapy, there was no recurrence of SRF. Conclusion CSCR is a rare side-effect noted following prolonged topical minoxidil therapy for androgenic alopecia. While we found oral eplerenone to be safe and effective, further studies would be required before it can be routinely used in the population.

Age-related alterations in the renin-angiotensin-aldosterone system (RAAS) have been reported in the cardiovascular system; however, the detailed mechanism of the RAAS component mineralocorticoid receptors (MR) has not been elucidated. The present study aimed to investigate the associations between MR and cardiac aging in rats, as well as the regulatory effects of oxidative stress and mitochondrial abnormalities in the aging process. MR expression in the hearts of male Sprague-Dawley rats aged 3 months (young rats) and 24 months (old rats) was evaluated in vivo. In addition, in vitro, H9C2 cells were treated with a specific MR antagonist, eplerenone, in order to investigate the molecular mechanism underlying the inhibition of myocyte aging process. The results demonstrated that MR expression was significantly higher in 24-month-old rat hearts compared with in 3-month-old rat hearts. These changes were accompanied by increased p53 expression, decreased peroxisome proliferator-activated receptor γ coactivator-1α expression, decreased mitochondrial renewal as assessed by electron microscopy, increased oxidative stress and decreased superoxide dismutase. In vitro, selective antagonism of MR partially blocked H2O2-induced myocardial aging as assessed by p16, p21 and p53 expression levels and excessive reactive oxygen species (ROS) accumulation. These results indicated that increased MR expression may drive age-related cardiac dysfunction via mitochondrial damage, increased ROS accumulation and an imbalanced redox state.

To study the outcomes of subthreshold micropulse yellow laser (SML) and eplerenone (EP) therapy in central serous chorio-retinopathy (cCSCR).Retrospective study of 28 eyes of 27 patients undergoing SML and 20 eyes of 19 patients undergoing EP therapy.Median duration of follow-up was 8 months for SML and 4.5 months for EP group. Complete SRF resolution was seen in 12/28 (42.8%) eyes in SML and 4/20 (20%) in EP group. Six eyes in SML group and two eyes in EP group needed additional SML. No EP patients demonstrated hyperkalemia warranting stopping of therapy. Baseline visual acuity (VA) was correlated positively with final VA in both groups. Presence/absence of focal leaks had differing outcomes in both treatment groups in terms of anatomical resolution.Both treatment modalities were effective in the management of cCSCR showing comparable favorable anatomical outcomes, but visual outcomes were not significant, probably due to chronicity of the pathology.

It has been suggested that aldosterone breakthrough during treatment with a type 1 angiotensin II receptor (AT1R) blocker (ARB) may be an important risk factor for the progression of renal and cardiovascular disease. We examined whether the direct renin inhibitor, aliskiren caused aldosterone breakthrough in angiotensin II (Ang II)-dependent hypertensive mice. The effect of combination therapy with aliskiren and eplerenone was compared with that of therapy using renin–angiotensin system (RAS) blockade. Tsukuba hypertensive mice were treated for 12 weeks with aliskiren (30 mg/kg/day, i.p), candesartan (5 mg/kg/day, p.o), eplerenone (100 mg/kg/day, p.o) aliskiren and candesartan, aliskiren and eplerenone or candesartan and eplerenone. Blood pressure, urinary aldosterone and angiotensinogen (AGTN) excretion; plasma endothelin-1 concentration; kidney weight; urinary albumin excretion (UAE); glomerular injury; and renal messenger RNA (mRNA) levels for transforming growth factor (TGF)-β1, plasminogen activator inhibitor (PAI)-1, angiotensin-converting enzyme (ACE) and AT1R were measured. Combination therapy with aliskiren and candesartan caused a further decrease in blood pressure (p

LSD1 (lysine-specific demethylase-1) is an epigenetic regulator of gene transcription. LSD1 risk allele in humans and LSD1 deficiency ( LSD1 +/− ) in mice confer increasing salt-sensitivity of blood pressure with age, which evolves into salt-sensitive hypertension in older individuals. However, the mechanism underlying the relationship between LSD1 and salt-sensitivity of blood pressure remains elusive. Here, we show that LSD1 genotype (in humans) and LSD1 deficiency (in mice) lead to similar associations with increased blood pressure and urine potassium levels but with decreased aldosterone levels during a liberal salt diet. Thus, we hypothesized that LSD1 deficiency leads to an MR (mineralocorticoid receptor)-dependent hypertensive state. Yet, further studies in LSD1 +/− mice treated with the MR antagonist eplerenone demonstrate that hypertension, kaliuria, and albuminuria are substantially improved, suggesting that the ligand-independent activation of the MR is the underlying cause of this LSD1 deficiency–mediated phenotype. Indeed, while MR and epithelial sodium channel expression levels were increased in LSD1 +/− mouse kidney tissues, aldosterone secretion from LSD1 +/− glomerulosa cells was significantly lower. Collectively, these data establish that LSD1 deficiency leads to an inappropriate activation and increased levels of the MR during a liberal salt regimen and suggest that inhibiting the MR pathway is a useful strategy for treatment of hypertension in human LSD1 risk allele carriers.

The issues of diuretic therapy in patients with chronic kidney disease, pharmacokinetics of diuretics, the problem of diuretic resistance, the tactics of using thiazides and loop diuretics in patients with various stages of chronic kidney disease, according to the recommendations of the National Kidney Foundation Kidney Disease Outcomes Quality Initiative are discussed in the article. Particular attention is paid to the prescription of this group of drugs to patients with end stage renal disease, as well as those undergoing renal replacement therapy (hemodialysis).Diuretics play an important role in the management of patients with chronic kidney disease with the development of hypertension and an increased extracellular fluid volume. In case of impaired renal function leading place is given to loop diuretics. Their combination with thiazide diuretics can increase the diuretic effect. The results of clinical trials assessing the effectiveness of the use of diuretics during decline of residual renal function are provided. It is reported about the effect of potassium-sparing diuretics on the incidence of cardiovascular complications, the development of hyperkalemia in patients undergoing dialysis treatment. The importance of continuation of intensive study about the possibility of antagonists of mineralocorticoid receptors usage, in particular the spironolactone, eplerenone, and finerenone in order to reduce cardiovascular complications and mortality, is indicated.

Mineralocorticoid receptors (MRs) are implicated in the pathology of hypertension. MR blockers are recommended for the treatment of salt-sensitive or resistant hypertension. However, use of currently available MR blockers is limited by adverse events. This phase 3 multicenter, randomized, double-blind study compared the efficacy and safety of esaxerenone, a new selective nonsteroidal MR blocker, at 2.5 and 5 mg/day and eplerenone 50 mg/day in Japanese patients with essential hypertension. After a 4-week washout period, 1001 eligible adults with hypertension were randomized evenly to esaxerenone 2.5 or 5 mg/day or eplerenone 50 mg/day treatments, taken orally once daily for 12 weeks. Primary end points were changes in sitting systolic or diastolic blood pressure (BP) from baseline at the end of treatment. Esaxerenone 2.5 mg/day was noninferior to eplerenone for reductions in sitting and 24-hour BP. Reductions in BP with esaxerenone 5 mg/day were significantly greater than those with esaxerenone 2.5 mg/day. Changes in diurnal BP showed persistent 24-hour antihypertensive effects in all treatment groups. The proportions of patients achieving target sitting BP ( Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT02890173.

Background The p.Arg14del (c.40_42delAGA) phospholamban (PLN) pathogenic variant is a founder mutation that causes dilated cardiomyopathy (DCM) and arrhythmogenic cardiomyopathy (ACM). Carriers are at increased risk of malignant ventricular arrhythmias and heart failure, which has been ascribed to cardiac fibrosis. Importantly, cardiac fibrosis appears to be an early feature of the disease, occurring in many presymptomatic carriers before the onset of overt disease. As with most monogenic cardiomyopathies, no evidence-based treatment is available for presymptomatic carriers. Aims The PHOspholamban RElated CArdiomyopathy intervention STudy (iPHORECAST) is designed to demonstrate that pre-emptive treatment of presymptomatic PLN p.Arg14del carriers using eplerenone, a mineralocorticoid receptor antagonist with established antifibrotic effects, can reduce disease progression and postpone the onset of overt disease. Methods iPHORECAST has a multicentre, prospective, randomised, open-label, blinded endpoint (PROBE) design. Presymptomatic PLN p.Arg14del carriers are randomised to receive either 50 mg eplerenone once daily or no treatment. The primary endpoint of the study is a multiparametric assessment of disease progression including cardiac magnetic resonance parameters (left and right ventricular volumes, systolic function and fibrosis), electrocardiographic parameters (QRS voltage, ventricular ectopy), signs and/or symptoms related to DCM and ACM, and cardiovascular death. The follow-up duration is set at 3 years. Baseline results A total of 84 presymptomatic PLN p.Arg14del carriers (n = 42 per group) were included. By design, at baseline, all participants were in New York Heart Association (NHYA) class I and had a left ventricular ejection fraction > 45% and Conclusion iPHORECAST is a multicentre, prospective randomised controlled trial designed to address whether pre-emptive treatment of PLN p.Arg14del carriers with eplerenone can prevent or delay the onset of cardiomyopathy. iPHORECAST has been registered in the clinicaltrials.gov-register (number: NCT01857856).

Purpose: To compare the efficacy and safety between half-dose photodynamic therapy (PDT) and eplerenone therapy for treating chronic central serous chorioretinopathy (cCSC). Design: This was a multicenter, open-label, randomized controlled trial. Methods: This investigator-initiated trial was conducted in 3 academic medical centers in the Netherlands. Eligible patients were randomized at a 1:1 ratio to receive either indocyanine green angiography-guided half-dose PDT or oral eplerenone for 12 weeks. Both anatomical and functional outcomes were evaluated at 3 months after the start of treatment. Results: A total of 107 patients were randomly assigned to receive either half-dose PDT (n = 53) or eplerenone treatment (n = 54). Thirteen patients (3 in the PDT group and 10 in the eplerenone group) did not adhere to the study protocol. At the 3-month evaluation visit, 78% of patients in the PDT group had complete resolution of subretinal fluid accumulation compared to only 17% of patients in the eplerenone group (P < .001). Mean best-corrected visual acuity in Early Treatment of Diabetic Retinopathy Study letters at the 3-month evaluation visit was 83.7 ± 10.8 and 82.8 ± 9.0 in the PDT and eplerenone groups, respectively (P = .555). In addition, mean retinal sensitivity on microperimetry was 25.4 ± 3.4 dB and 23.9 ± 4.0 dB in the PDT and eplerenone groups, respectively (P = .041). Finally, mean vision-related quality of life scores were 87.2 ± 8.5 and 83.8 ± 12.1 in the PDT and eplerenone groups, respectively (P = .094). Three patients (6%) in the PDT group experienced adverse events during the study compared to 18 patients (33%) in the eplerenone group. Conclusions: Half-dose PDT is superior to oral eplerenone for cCSC with respect to both short-term safety and efficacy outcomes.

The VICI trial reported by Lotery et al. is a recent placebo-controlled, randomized trial that examined the efficacy of eplerenone treatment for chronic central serous chorioretinopathy (CSCR) in 104 patients. The study found no significant difference in best-corrected visual acuity (BCVA) between the eplerenone-treated and placebo groups, prompting the VICI investigators to conclude that eplerenone should not be prescribed to treat CSCR. Limitations of the study include the patients' high baseline BCVA, use of a functional outcome like BCVA as the primary endpoint instead of an anatomical outcome, failure to account for rebound effect, and measuring subretinal fluid (SRF) thickness instead of the more informative SRF volume. Based on these reasons and evidence from multiple case series and prospective studies over the past 7 years, it is the opinion of the authors of this editorial that the VICI investigators' conclusion to stop prescribing eplerenone for CSCR is too severe. Future clinical trials should continue to explore the potential for eplerenone as long-term maintenance treatment in chronic CSCR. [ Ophthalmic Surg Lasers Imaging Retina . 2021;52:308–310.]

BACKGROUND Focal segmental glomerulosclerosis (FSGS) predisposes patients for risk of recurrent disease in allografts. METHODS We report a case of a recipient of an unrelated living donor renal transplant and discuss considerations for utilization of ofatumumab and eplerenone in treatment for recurrent FSGS. RESULTS The recipient was initially managed with scheduled plasmapheresis, intravenous immunoglobulin (IVIG), and rituximab post-transplant during index hospitalization. With notable recurrence of FSGS noted on kidney transplant biopsy, she was initially treated with additional plasmapheresis sessions leading to downtrend in proteinuria. The patient was then transitioned to LDL-A pheresis, which resulted again in uptrend in proteinuria. This prompted return to scheduled plasmapheresis sessions weekly, leading again to a downtrend in proteinuria. Albumin levels remained within normal range throughout her course. Following initiation of eplerenone and ofatumumab, the patient demonstrated normalization of urine protein:creatinine ratio and remission of FSGS recurrence without need for additional apheresis. CONCLUSIONS With notable risk of recurrence of FSGS in kidney transplants leading to allograft failure, the use of ofatumumab and eplerenone in conjunction should be considered for management to induce remission.

Background There is little evidence on the use of subcutaneous furosemide infusions in heart failure patients, especially in the community setting (Beattie & Johnson, 2012). Integrated working is key to smooth the transition from management in the hospital to community settings, particularly for patients who are increasingly fatigued with short prognoses but who may still benefit from parenteral therapy. Aim To retrospectively evaluate clinical effectiveness of subcutaneous furosemide used in the community setting at end-of-life. Method We reviewed case notes of patients treated with continuous subcutaneous furosemide by the community palliative care team (2019–2021). A standardised proforma was used to assess patient demographics, indications, clinical outcomes and barriers/facilitators to the process. Results 16 patients received a total 22 interventions. Median age 77(50-94), 11(69%) male, primary HF (Heart failure) diagnosis 6 HFrEF, 5 HFpEF,2 RHF, 2 Valvular, 1 unknown aetiology. Phase of Illness, 13 unstable and 9 deteriorating with AKPS 30-60%. Oral diuretics included loop diuretics (furosemide 15/22 and bumetanide 6/22), aldosterone receptor antagonists (spironolactone 4/22), mineralocorticoid receptor antagonists (eplerenone 11/22) and thiazides (indapamide 1/22). Majority of interventions had stage 3 renal function (16/22 episodes). Patients were discussed with cardiology or palliative care consultant. Median dose given was 160mg (range 80-240mg) for 11(1-33) days. Outcomes 15/22 showed symptomatic improvement, 6/22 had side-effects including worsening renal function, hypotension, hypokalaemia and site reaction needing antibiotics. 21/22 interventions avoided a hospital admission; 12/16 patients achieved preferred place of death (1 was admitted to hospital; 3 alive). Barriers to community administration included: challenges obtaining medications, burden of a continuous sub cutaneous infusion [CSCI]. Conclusion There is a clear benefit for individual patients, allowing those in last year of life to spend as much time as possible at home. We plan to develop a decision support tool to aid wider community decision making, facilitating timely use of subcutaneous furosemide, therefore maintaining effective symptom control in community settings.

Introduction Resistant hypertension (RH) is more prevalent in the advanced stages of chronic kidney disease (CKD) and contributes to a greater likelihood of poor cardiovascular and renal outcomes. However, RH often goes untreated in this population as the currently available recommended add-on therapy, steroidal mineralocorticoid receptor antagonists (MRAs) such as spironolactone and eplerenone, may lead to unacceptable side effects, mainly hyperkalemia in a cohort with reduced kidney function. KBP-5074 is a novel non-steroidal MRA that addresses the unmet need of treating RH in the CKD population without hyperkalemia. Areas covered We provide an overview of the current state of RH treatment in stage 3B/4 CKD as it relates to available steroidal MRAs and the current limitations of this treatment. We then explore the emerging data on nonsteroidal MRAs, particularly the novel agent KBP-5074 and its applicability to treatment in this context. Expert opinion In a randomised, double-blind, placebo-controlled phase 2b trial, the novel nonsteroidal MRA KBP-5074 demonstrated clinical efficacy and safety in treating RH in stage 3B/4 CKD and offers a potential new treatment option in this population at high risk for cardiovascular disease (CVD) and CKD progression.

Background The study examined the efficacy of eplerenone in the management of chronic central serous chorioretinopathy (CSCR) with the aim of short-term observations. The study also aimed at observing changes in optical coherence tomography (OCT) parameters and visual acuity. Methodology This retrospective study was conducted at Layton Rahmatulla Benevolent Trust (LRBT) Eye Hospital from September 2019 to October 2020. A thorough ocular examination, color fundus photographs, fluorescein angiography, and macular OCT were performed on all patients. We administered one tablet of 50 mg eplerenone on day one and further advised the use of the same dose for 30 days. After the administration of the tablet, the patients were further analyzed on weeks one, two, and four. On every visit, we examined ophthalmic conditions by visual acuity, slit lamp, and dilated fundus examinations along with macular OCT and measured blood pressure. At follow-up, we measured the levels of serum creatinine at weeks one and four. Student's t-test and chi-square test were used for normal distribution and nominal variables. A p-value < 0.05 was considered statistically significant in all the analyses. Results A total of 15 patients were selected for this research, but unfortunately, two of them withdrew amid the study. For the remaining 13 patients, the mean duration of observing symptoms was three months and three weeks. At one-month follow-up, the mean subretinal fluid (SRF) height (94.18 μm) decreased, but we did not find any statistical significance between the SRF height at one-month follow-up and baseline (113.15 μm). In four patients, the SRF height increased up to 3-30 μm after four months of treatment. In our study, we found some negative consequences of eplerenone therapy in terms of hypertension, cramps, nausea, and migraine. Conclusion We concluded that short-term eplerenone treatment assists in the reduction of the choroidal thickness (CT) and central macular thickness (CMT) among patients with central serous chorioretinopathy. However, eplerenone treatment failed to decrease subretinal fluid height and does not bring any significant improvement in the visual acuity of patients. Some mild adverse effects of the treatment include hypertension, abdominal cramps, nausea, and migraine.