Eplerenone Group Research Articles

Micropulse Laser versus Eplerenone for Chronic Central Serous Chorioretinopathy: A 12-Month Comparison.

To compare the long-term efficacy of navigated subthreshold micropulse laser (NSML) and continuous oral eplerenone (EPL) in chronic central serous chorioretinopathy (cCSC). This retrospective observational study included 44 eyes with cCSC (EPL: n = 26; NSML: n = 18). Best-corrected visual acuity (BCVA), central macular thickness (CMT), subretinal fluid (SRF) height, and subfoveal choroidal thickness (SFCT) were evaluated over 12months. Both groups showed significant improvements in BCVA and CMT (p < 0.05). Complete SRF resolution was achieved in both groups by 12months, with NSML showing faster resolution (2.77 ± 1.43 vs. 6.34 ± 2.17months, p < 0.001). The EPL group demonstrated significant SFCT reduction at 6 and 12months (p = 0.001), while the NSML group showed no significant SFCT changes (p > 0.05). Both NSML and EPL improved retinal morphology and visual function in patients with cCSC. NSML achieved faster SRF resolution, while EPL resulted in more significant choroidal thickness reduction. These findings suggest distinct mechanisms of action: NSML primarily affects the retinal pigment epithelium, while EPL modulates choroidal vasculature. Treatment choice may depend on individual patient characteristics and treatment goals.

Therapies for Central Serous Chorioretinopathy: A Report by the American Academy of Ophthalmology

To assess the safety and efficacy of the multiple therapeutic modalities for the treatment of central serous chorioretinopathy (CSCR). A literature search of English-language studies in the PubMed database with no date restrictions was last conducted in May 2024. The combined searches yielded 612 citations, 31 of which were selected for full-text review and for inclusion in this assessment. The panel methodologist assigned a level of evidence rating to each study. Six were assigned a level I rating, 23 were assigned a level II rating, and 2 were assigned a level III rating. Studies were categorized based on treatment modalities: laser-based therapy, intravitreal therapy, laser-based therapy versus intravitreal therapy, and systemic therapies. Within those categories, they were separated based on treatments for acute versus chronic CSCR. One level I study showed that photodynamic therapy (PDT) using half-dose verteporfin for acute CSCR led to a significant decrease in subretinal fluid (SRF) with 95% of treated patients having no SRF at 12 months compared with 58% of untreated eyes with acute CSCR (P= 0.001). Anatomically, the mean CFT at 1 year was significantly lower in the treated group (161 ± 65 μm) versus the observation group (278 ± 92 μm) (P= 0.001). A second level I study compared half-dose verteporfin PDT versus 30%-dose verteporfin PDT and found that 94.6% in the half-dose PDT group had no SRF at 12 months compared with 75.4% in the 30%-dose PDT group (P= 0.004). The noninferiority of the 30%-dose PDT compared with half-dose PDT was not demonstrated. The VICI trial was a level I study that found no benefit with the use of mineralocorticoid antagonism with eplerenone for the treatment of chronic CSCR. With respect to the primary outcome of visual acuity (VA), the VICI trial found no significant difference at 12 months: 79.5 letters in the placebo group and 80.4 letters in the eplerenone group (P= 0.24). In general, the results from the other evaluated studies were inconsistent and thus inconclusive. There were no level I studies that supported the role of intravitreal anti-VEGF injections or systemic beta-blockers for patients with CSCR. A small level I study showed potential efficacy of Helicobacter pylori therapy for CSCR. There is evidence to support half-dose PDT for the treatment of acute CSCR regarding anatomic improvement, but less robust evidence supports improvement in VA or sustained anatomic benefit beyond 12 months. Intravitreal anti-VEGF injections and oral beta-blockers demonstrate inconsistent anatomic and visual benefits in patients with CSCR. The mineralocorticoid antagonist eplerenone has not been demonstrated as efficacious for treatment of chronic CSCR. The treatment of H.pylori infection may have some anatomic and visual benefit in the treatment of either acute or chronic CSCR. Acute CSCR resolves spontaneously without treatment in most eyes. Proprietary or commercial disclosure may be found after the references.

Comparative Analysis of The Effectiveness of Antihypertensive Therapy Including Spironolactone and Eplerenone in Patients With Essential Hypertension and Atrial Fibrillation.

To perform a comparative analysis of the efficacy of antihypertensive therapy (AHT) containing spironolactone or eplerenone in patients with essential arterial hypertension (AH) and atrial fibrillation (AF). The study included 99 male and female patients with essential AH complicated by permanent AF, who were receiving the outpatient treatment at the National Specialized Scientific and Practical Medical Center of Cardiology (Tashkent). The patients aged 61.3±9.5 years, the mean duration of AH was 12.9±8.3 years. All patients were divided into two groups: Group 1, patients who completed a 6-month combination AHT containing spironolactone (n=51); Group 2, patients who completed a 6-month combination AHT containing eplerenone (n=48). AF was diagnosed by electrocardiogram (ECG) and/or 24-hour ECG monitoring according to standard diagnostic criteria. The ECG study was performed in compliance with the American Society of Echocardiography Guidelines in M- and B-modes. The degree of structural vascular alterations was determined by the intima-media thickness of the common carotid artery by duplex scanning and microalbuminuria in morning urine. The concentrations of sex hormones were measured by the enzyme immunoassay. The serum concentrations of lipids, glucose, creatinine, and uric acid were measured by the enzymatic method. The glomerular filtration rate (GFR) was calculated with the EPI formula. Results of all studies were considered statistically significant at p&lt;0.05. The proportion of patients who achieved the target diastolic blood pressure (BP) values was significantly greater in the eplerenone-containing treatment group than in the spironolactone-containing treatment group: 87.8% vs. 67.5% (p=0.043). The proportion of patients who simultaneously achieved the target systolic and diastolic BP values was slightly greater in the eplerenone-containing treatment group than in the spironolactone-containing group (100% vs. 92.1%, p=0.060). The best cardioprotective efficacy was observed in the group of combination AHT containing eplerenone. Specifically, in Group 2, the left ventricular ejection fraction (LVEF) was significantly improved compared to Group 1: from 55.4±10.6% at baseline to 52.6±9.1% in Group 1 (p&gt;0.05) and from 54.8±8.8% at baseline to 58.2±6.4% in Group 2 (p&lt;0.02). Only in Group 2, the left atrial volume index (LAVI) was significantly decreased compared to Group 1. Thus, in Group 1, the LAVI changed from 42.2±15.1 ml/m2 at baseline to 40.4±12.2 ml/m2 (p&gt;0.05) and in Group 2, from 41.2±15.3 ml/m2 at baseline to 37.3±13.5 ml/m2 after the treatment (p&lt;0.05); the ∆% LAVI in the eplerenone group was -5.9% vs. -0.36% in the spironolactone group. In men of Group 1, estradiol significantly increased from 13.9±12.6 pmol/l at baseline to 22.7±12.4 pmol/l (p&lt;0.001). The good antihypertensive efficacy of the 6-month combination therapy containing eplerenone was significantly superior to spironolactone in achieving the target BP values. The eplerenone-containing treatment significantly improved LVEF and decreased LAVI compared to the spironolactone-containing treatment. A trend towards a beneficial effect of the AHT containing eplerenone on concentrations of sex hormones was noted in both women and men.

Inhibitory effects of Eplerenone on angiogenesis via modulating SGK1/TGF-β pathway in contralateral kidney of CKD pregnancy rats

BackgroundEplerenone is a selective aldosterone receptor blocker that is effective in preventing the progression of chroinic kidney disease (CKD). However, its mechanism and role in CKD pregnancy still remain uncertain. The aim of this study was to evaluate whether eplerenone could attenuated the fibrosis of unilateral ureteral obstruction (UUO) pregnant rats' contralateral kidney, improved pregnancy outcome and explore its therapeutic mechanisms. MethodsA pregnancy rat model of UUO established, female Wistar rats were randomly assigned into sham-operated group (Sham group),sham-operated combined pregnancy group (SP group), unilateral ureteral obstruction combined pregnancy group (UUO + Pregnancy group), unilateral ureteral obstruction combined pregnancy, administered eplerenone (UUO + Pregnancy+Eplerenone group). On the 18th day of pregnancy, the rats were placed in a metabolic cage, 24 h urine was collected and stored at −80 °C. Next day, all animals were euthanized, and serum was collected by centrifugation and stored at −20 °C. Then the right kidney was extracted, a part of the kidney was placed in 4% paraformaldehyde for morphology, immunohistochemical staining, and immunofluorescence staining, and the other part was placed in a − 80 °C refrigerator for RNA and protein extraction. In vitro, HUVECs was treated with aldosterone, progesterone and estradiol, VEGFA and its receptor blocker bevacizumab. The ability of proliferation, migration and tubularization of HUVECs was detected by CCK-8, scratch wound assay and endothelial tube formation assay. And the co-expression of CD34 and α-SMA of HUVECs was detected by Flow cytometry. ResultsImmunofluorescence results showed that the co-expression of CD34 and α-SMA increased in the UUO + Pregnancy group was significantly increased. The expression of SGK-1, TGFβ-1, Smad2, Smad3, VEGF-A, VEGFR2, CD34, α-SMA and Collagen I was significantly higher in the kidneys of the UUO + Pregnancy group compared to the Sham group and SP group. Eplerenone inhibited the expression of those results. In vitro, the ability of proliferation, migration and tubularization was increased after treated with aldosterone, aldosterone with progesterone and estradiol or VEGFA. Similarly, the expression of α-SMA on the surface of HUVECs treated with aldosterone, aldosterone with progesterone and estradiol were increased, while eplerenone supressed its expression. ConclusionEplerenone inhibits renal angiogenesis by blocking the SGK-1/TGFβ signal transduction pathway, thereby inhibiting the phenotypic transformation of endothelial cells, slowing down renal fibrosis, and reducing kidney damage caused by pregnancy.

Huoxue Jiedu Huayu recipe inhibits macrophage-secreted vascular endothelial growth factor-a on angiogenesis and alleviates renal fibrosis in the contralateral kidneys of unilateral ureteral obstruction rats.

Male Wistar rats were randomly divided into 4 groups: the sham group, UUO group (180 d of left ureter ligation), UUO plus eplerenone (EPL) group, and UUO plus HJHR group. After 180 d of oral drug administration, blood and contralateral kidneys were collected for analysis. Angiogenesis- and fibrosis-related indexes were detected. HJHR and EPL improved structural damage and renal interstitial fibrosis in the contralateral kidney and reduced the protein expression levels of α-smooth muscle actin (α-SMA), vimentin and collagen I. Moreover, these treatments could reduce the expression of vascular endothelial growth factor-A (VEGFA) by inhibiting the infiltration of macrophages. Furthermore, HJHR and EPL significantly reduced the expression of CD34 and CD105 by downregulating VEGFA production, which inhibited angiogenesis. Finally, the coexpressions of CD34, CD105 and α-SMA were decreased in the HJHR and EPL groups, indicating that endothelial-to-mesenchymal transition was inhibited. These findings confirm that HJHR alleviates contralateral renal fibrosis by inhibiting VEGFA-induced angiogenesis, encourage the use of HJHR against renal interstitial fibrosis and provide a theoretical basis for the clinical management of patients with CKD.

EPLERENONE VS IRBESARTAN AS FIRST LINE THERAPY IN OBESE HYPERTENSIVE PATIENTS: PRELIMINARY RESULTS OF HEBRO TRIAL IN ECHOCARDIOGRAPHIC DIASTOLIC FUNCTION INDEXES

Objective: Obesity is significantly associated with hypertension and cardiovascular outcomes. However, little is known about the impact of aldosterone blockade using eplerenone on hypertensive obese patients as first line therapy. The aim of this study is to compare the efficacy between eplerenone-based strategy and irbesartan-based strategy in obese hypertensive individuals, regarding blood pressure reduction and change of echocardiographic diastolic function parameters. Design and method: HEBRO (antiHypertensive treatment with Eplerenone vs. irBesartan in hypeRtensive Obese patients) is a prospective, randomized, open-labeled, multicenter trial enrolled 112 obese hypertensive patients aged 30-75 years old, evaluated by office and out-of-office BP measurements. Patients were randomized to either 25 mg eplerenone twice (59) or 150 mg irbesartan (53) once daily. The primary endpoint is the difference in ambulatory BP measurements after 6 months follow-up period and secondary endpoint is difference in diastolic function parameters. Results: We enrolled 112 patients, 54.6 years old, 53% female, mean BMI 34.4 kg/m2 and mean eGFR 82.5 ml/min/1.73m2. Diastolic function was assessed at baseline and 6 months, by calculating left ventricular mass index (LVMI) and left atrial volume index (LAVI). At baseline, mean LVMI was 102.9 g/m2 ± 18.1 in the irbesartan group vs. 110.1 g/m2 ± 30.5 in the eplerenone group, p=0.237. The change of LVMI was – 5.6 ± 17.8 vs. -4.5 ± 22.6, p=0.843. At baseline, mean LAVI was 30.6 ml/m2 ± 16.9 in the irbesartan group vs. 30.7 ml/m2 ± 11.1 in the eplerenone group, p=0.979. The change of LAVI in the two study arms was +0.9 ± 6.7 vs. -3.6 ± 11.5, p=0.063, respectively. Although, the result was not statistically significant, there was a numerical trend towards the eplerenone arm. Conclusions: There were no statistically significant differences at baseline and follow-up evaluation of changes in left ventricular and left atrial geometry, though there is a numerical trend towards eplerenone arm, regarding reduction of LAVI after 6 months follow-up period. Patients are currently still enrolled and data on larger pool are anticipated.

Abstract 15021: Effect of Eplerenone on Cardiac Reverse Remodeling in Patients With Acute Heart Failure: A Sub-Analysis of the Earlier Randomized Double-Blind Trial

Background: Activation of the renin-angiotensin-aldosterone system promotes left ventricular (LV) remodeling and dysfunction. In the EARLIER trial, we reported that the early initiation of eplerenone in patients with acute heart failure (AHF) reduced re-hospitalization for heart failure; however, its effect on cardiac reverse remodeling remains unclear. Hypothesis: Eplerenone attenuates LV remodeling in AHF patients with reduced ejection fraction (EF). Methods: In the EARLIER trial, hospitalized AHF patients with reduced EF (n = 300) were assigned randomly to either eplerenone (n = 149) or placebo (n = 151), once daily for 24 weeks. In this post-hoc analysis, absolute change in LVEF from baseline to 24 weeks was assessed by analysis of covariance adjusted for the baseline data. All participants treated with the study drug at least once were included in the analysis (eplerenone n=148, placebo n=149). Results: The absolute change in LVEF was not statistically different between the eplerenone and placebo groups (least square mean [LSM]difference: 2.81 ± 1.49, 95% CI: –1.25-5.21, P=0.06). The etiology of AHF consisted of acute myocardial infarction (AMI) (n=35) and non-AMI (n=265). LVEF was significantly improved by eplerenone in AMI patients (LSM difference: 8.04 ± 3.49, 95% CI: 0.90-15.18, P&lt;0.05), but did not in non-AMI patients (LSM difference: 1.98 ± 1.64, 95% CI: –1.25-5.21, P=0.23). Eplerenone showed a 39% reduction in CV death and HF hospitalization in AHF patients with non-AMI, despite no significant difference compared with the placebo (Hazard ratio:0.61, 95% CI: 0.24-1.57, P=0.30). Conclusions: Treatment with a mineralocorticoid receptor antagonist of eplerenone for 24 weeks induced LV reverse remodeling in AHF patients with reduced EF due to AMI. Further extended observation is needed to investigate the effect of eplerenone on LV remodeling in AHF patients with reduced EF due to non-AMI.

Initiation of eplerenone or spironolactone, treatment adherence, and associated outcomes in patients with new-onset heart failure with reduced ejection fraction: a nationwide cohort study.

The mineralocorticoid receptor antagonists (MRAs) eplerenone and spironolactone are beneficial in heart failure with reduced ejection fraction (HFrEF), but have not been prospectively compared. We compared clinical outcomes, daily dosages, and discontinuation rates for the two drugs in a nationwide cohort. We identified all patients with HFrEF in the period 2016-2020, who were alive and had initiated MRA treatment at study start, 180 days after HF diagnosis. We estimated the 2-year risk of a composite of death and HF hospitalization, as well as each component separately, using Kaplan-Meier, cumulative incidence functions, and Cox proportional hazards models adjusted for age, sex, and comorbidities. Secondly, we assessed treatment withdrawal, cross-over, and daily drug dosage. We included 7479 patients; 653 (9%) on eplerenone and 6840 (91%) on spironolactone. Patients in the eplerenone group were younger (median age 65vs. 69 years), and more often men (91%vs. 68%), both P<0.001. In adjusted analyses, with spironolactone as reference, there were no differences in the risk of the composite of all-cause death and HF hospitalization (HR 1.02, 95% CI 0.82-1.27), all-cause death (HR 0.93, 95% CI 0.67-1.30), or HF hospitalization (HR 1.10, 95% CI 0.84-1.42). Treatment withdrawal occurred in 34% in the eplerenone group and 53% in the spironolactone group (P<0.001), treatment cross-over in 3%, and 10%, respectively. Daily dose >25mg at 12 months, was observed in 230 patients (37%) in the eplerenone group and 771 patients (12%) in the spironolactone (P<0.001). In a contemporary nationwide cohort of patients with new-onset HFrEF who initiated MRA, we found no differences in clinical outcomes associated with initiation of eplerenone vs. spironolactone. Treatment was more frequently withdrawn, and daily drug dosage was lower among patients treated with spironolactone.

Efficacy and Safety of Eplerenone for Treating Chronic Kidney Disease: A Meta-Analysis.

In recent years, a large amount of clinical evidence and animal experiments have demonstrated the unique advantages of mineralocorticoid receptor antagonists (MRA) for treating chronic kidney disease (CKD). Accordingly, the present study aimed to systematically assess the second-generation selective MRAs eplerenone's safety and effectiveness for treating CKD. Four databases (PubMed, The Cochrane Library, Embase, and Web of Science) were searched for randomized controlled trials (RCT) correlated with eplerenone for treating CKD up to September 21, 2022. By complying with the inclusion and exclusion criteria, literature screening, and data extraction were conducted. A total of 19 randomized controlled articles involving 4501 cases were covered. As suggested from the meta-analysis, significant differences were reported with the 24-h urine protein (MD = -42.23, 95% confidence interval [CI] = -76.72 to -7.73, P = 0.02), urinary albumin-creatinine ratio (UACR) (MD = -23.57, 95% CI = -29.28 to -17.86, P < 0.00001), the systolic blood pressure (SBP) (MD = -2.73, 95% CI = -4.86 to -0.59, P = 0.01), and eGFR (MD = -1.56, 95% CI = -2.78 to -0.34, P = 0.01) in the subgroup of eplerenone vs placebo. The subgroups of eplerenone vs placebo (MD = 0.13, 95% CI = 0.07 to 0.18, P < 0.00001) and eplerenone vs thiazide diuretic (MD = 0.18, 95% CI = 0.13 to 0.23, P < 0.00001) showed the significantly increased potassium levels. However, no statistical significance was reported between the eplerenone treatment groups and the control in the effect exerted by serum creatinine (MD=0.03, 95% CI = -0.01 to 0.07, P = 0.12) and diastolic blood pressure (DBP) (MD = 0.11, 95% CI = -0.41 to 0.63, P = 0.68). Furthermore, significant risks of hyperkalemia were reported in the eplerenone group (K+ ≥ 5.5 mmol/l, RR = 1.70, 95%CI = 1.35 to 2.13, P=<0.00001; K+≥6.0 mmol/l, RR = 1.61, 95% CIs = 1.06 to 2.44, P = 0.02), respectively. Eplerenone has beneficial effects on CKD by reducing urinary protein and the systolic blood pressure, but it also elevates the risk of hyperkalemia.

Effect of 11-Deoxycorticosterone in the Transcriptomic Response to Stress in Rainbow Trout Skeletal Muscle.

In aquaculture, many stressors can negatively affect growth in teleosts. It is believed that cortisol performs glucocorticoid and mineralocorticoid functions because teleosts do not synthesize aldosterone. However, recent data suggest that 11-deoxycorticosterone (DOC) released during stress events may be relevant to modulate the compensatory response. To understand how DOC modifies the skeletal muscle molecular response, we carried out a transcriptomic analysis. Rainbow trout (Oncorhynchus mykiss) were intraperitoneally treated with physiological doses of DOC in individuals pretreated with mifepristone (glucocorticoid receptor antagonist) or eplerenone (mineralocorticoid receptor antagonist). RNA was extracted from the skeletal muscles, and cDNA libraries were constructed from vehicle, DOC, mifepristone, mifepristone plus DOC, eplerenone, and eplerenone plus DOC groups. The RNA-seq analysis revealed 131 differentially expressed transcripts (DETs) induced by DOC with respect to the vehicle group, mainly associated with muscle contraction, sarcomere organization, and cell adhesion. In addition, a DOC versus mifepristone plus DOC analysis revealed 122 DETs related to muscle contraction, sarcomere organization, and skeletal muscle cell differentiation. In a DOC versus eplerenone plus DOC analysis, 133 DETs were associated with autophagosome assembly, circadian regulation of gene expression, and regulation of transcription from RNA pol II promoter. These analyses indicate that DOC has a relevant function in the stress response of skeletal muscles, whose action is differentially modulated by GR and MR and is complementary to cortisol.

PS-B08-4: CHRONIC INTERMITTENT HYPOXIA INDUCES RENAL FIBROSIS BY MR ACTIVATION

Purpose: Obstructive sleep apnea is mainly characterized by chronic intermittent hypoxia (CIH), which is associated with chronic kidney disease. Macrophage is known to play an important role in renal fibrosis. However, little is known of the potential role of macrophage-to-myofibroblast transition (MMT) in hypoxic conditions. The aim of this study was to understand how infiltrating macrophages may contribute to renal fibrosis in hypoxic conditions. Methods: In this study, 30 adult male sprague dawley (SD) rats were randomly divided into normoxic control(NC), chronic intermittent hypoxia(CIH), and eplerenone(EPL) groups-each containing ten rats. The CIH and EPL groups were exposed to hypoxia in a commercial hypoxic chamber for 5 weeks. Rats in the EPL group were administered EPL orally via diet for 5 weeks. All rats were then sacrificed and serum, 24-hour urine and tissue specimens were collected for renal function, histopathology, western blot, immunohistochemistry. The RAW264.7 macrophages were subjected to 24 hours of hypoxia and 12 hours of reoxygenation. Cells were collected for immunofluorescence staining. Results: In addition to blood pressure, renal aldosterone level was also increased in CIH rats. Massons trichrome and Sirius red staining showed significantly higher collagen deposition and fibrosis in CIH rats. A markedly increased co-expression of α-SMA and CD68 in vitro and in vivo after CIH exposure. MR nuclear translocation was seen in hypoxic macrophages. Western blot showed that the expression of SGK-1 and p-SGK-1 was upregulated. These effects were reversed by MR blocker (EPL). Conclusions: CIH-induced macrophage infiltration, an important source of myofibroblasts, might participate in the development of renal interstitial fibrosis. These effects were reversed by EPL. Therefore, we speculate MR activation may be related to CIH-induced renal fibrosis.

Functionality of retinal vessels in central serous retinopathy: A comparison between eplerenone and photodynamic therapy.

To investigate retinal vessels functionality in patients with acute central serous chorioretinopathy (CSC) undergoing oral eplerenone or photodynamic therapy (PDT) using Retinal Vessel Analyzer (RVA) and Dynamic Vessel Analyzer (DVA), respectively. Treatment naïve acute CSC patients presenting between May 2017 and June 2017 were recruited. A complete ophthalmological examination was performed in all participants before and after oral eplerenone (eplerenone group) or half-dose PDT (PDT group). Eighteen eyes of 18 patients affected by acute CSC underwent either oral eplerenone (10 eyes of 10 patients, 47.6 ± 8.9 years old) or half-dose PDT (8 eyes of 8 patients, 57.4 ± 6.2 years old), respectively. After 2 months of treatment, non-significant variations of static retinal vessels analysis, dynamic arterial and venous dilatation were reported in eplerenone group. Similarly, in PDT group non-significant variations of static retinal vessels analysis, dynamic arterial and venous dilatation were found after 2 months of treatment. Static and dynamic retinal functionalities in acute CSC may not be significantly improved by oral eplerenone and half-dose PDT. Although their choroidal effects, these treatments could not exert a significant effect on retinal vessels motility. Thus, both local and systemic therapies might not help avoiding the onset of vascular and other retinal known alterations of CSC.

OCT-A in chronic central serous chorioretinopathy treated with oral eplerenone and half-fluence photodynamic therapy: A comparative study.

To evaluate retinal and choriocapillary vessel density (VD) changes in patients with chronic central serous chorioretinopathy (CSC) treated with half-fluence verteporfin photodynamic therapy (vPDT) or eplerenone, using optical coherence tomography angiography (OCTA). Patients affected by CSC and treated with vPDT and eplerenone were retrospectively studied. At baseline and 3 months after each treatment, all patients underwent a complete ophthalmological examination, including an evaluation of best-corrected visual acuity (BCVA), slit-lamp biomicroscopy, fundus examination, fluorescein angiography (FA), indocyanine green angiography (ICGA), spectral-domain optical coherence tomography (SD-OCT) and OCTA. Forty-eight eyes of patients with CSC were analysed. Twenty-four eyes were placed in the vPDT group, and 24 eyes formed the eplerenone group. In both groups, OCTA showed a significant improvement in the VD of deep capillary plexus (DCP) and choriocapillaris (CC) after treatments with respect to baseline (p < 0.001), whereas the VD of superficial capillary plexus (SCP) did not show significant differences (p > 0.05). The PDT group demonstrated a statistically significant increase in the VD of DCP and CC with respect to the eplerenone group (DCP p = 0.012; CC p = 0.004). A statistically significant reduction with respect to baseline in subfoveal choroidal thickness (SFCT) (p = 0.001 for vPDT group; p = 0.001 for eplerenone group) and in central foveal thickness (CFT) (p = 0.001 for vPDT group; p = 0.001 for eplerenone group) was also found. The SFCT was significantly thinnest in the PDT group with respect to the eplerenone group (p = 0.021). OCTA allowed us to study retinal and choriocapillary vascular changes in patients with CSC treated with vPDT and eplerenone.

Long-term follow-up of chronic central serous chorioretinopathy patients after primary treatment of oral eplerenone or half-dose photodynamic therapy and crossover treatment: SPECTRA trial report No. 3

PurposeComparing anatomic and functional efficacy and safety of primary treatment with either half-dose photodynamic therapy (PDT) or oral eplerenone, or crossover treatment in chronic central serous chorioretinopathy patients.MethodsAfter the SPECTRA trial baseline visit, patients were randomized to either half-dose PDT or eplerenone and received crossover treatment if persistent subretinal fluid (SRF) on optical coherence tomography (OCT) was present at first follow-up (at 3 months). Presence of SRF and best-corrected visual acuity (BCVA) was evaluated at 12 months.ResultsOut of the 90 patients evaluated at 12 months, complete SRF resolution was present on OCT in 43/48 (89.6%) of patients who were primarily randomized to half-dose PDT and in 37/42 (88.1%) who were primarily randomized to eplerenone. Out of the 42 patients that were primarily randomized to eplerenone, 35 received crossover treatment with half-dose PDT. The BCVA improved significantly more at 12 months in patients who had received primary half-dose PDT as compared to the primary eplerenone group (p = 0.030).ConclusionsTwelve months after baseline visit, most patients treated with half-dose PDT (either primary or crossover treatment) still had complete SRF resolution. The long-term BCVA in patients who receive primary half-dose PDT is better than in patients in whom PDT is delayed due to initial eplerenone treatment with persistent SRF.

EPLERENONE VS IRBESARTAN AS FIRST LINE THERAPY IN OBESE HYPERTENSIVE PATIENTS: PRELIMINARY RESULTS FROM HEBRO STUDY

Objective: Obesity is significantly associated with adverse cardiovascular outcomes. The relationship between obesity and hypertension is well described with obese patients having two times the incidence of developing increased blood pressure (BP). However, little is known about the impact of aldosterone blockade using eplerenone on hypertensive obese patients as first line therapy. The aim of this study was to compare the efficacy between eplerenone and irbesartan in obese hypertensive subjects. Design and method: A prospective, randomized, open-labeled, multicenter trial enrolled 54 hypertensive patients aged 30 to 75 years old, with obesity [body mass index BMI &gt; or = 30 kg/m2)], evaluated by home BP, office BP and ambulatory BP measurements. Subjects randomly received 25 mg eplerenone twice daily or 150 mg irbesartan every morning. The primary endpoint were systolic and diastolic BP after 2 months of follow up. Results: In 54 hypertensive obese patients [53.7% women, mean age 55.8 ± 10.9 years, BMI 34.6 ± 3.1 kg/m2, mean office BP 146.4 ± 9.7/91.8 ± 9.8 mmHg and mean ABP 140.9 ± 7.9/84.6 ± 8.2 mmHg] there was no significant difference in the reduction of systolic ABP between irbesartan and eplerenone (11 ± 14.8 vs. 7 ± 14.7, p = 0.11), nor in the reduction of diastolic ABP (5 ± 8.3 vs. 3.8 ± 9.7, p = 0.13). Moreover, there was no difference in the reduction of OBP in irbesartan group (12 ± 11.3 vs. 9.4 ± 12.7, p = 0.14) in comparison with eplerenone group (7.1 ± 8.7 vs. 2.8 ± 8.7, p = 0.11). Also, there was no statistical significant change in renal function parameters and electrolytes levels in both groups Conclusions: this study suggests that eplerenone does not differ in efficacy and safety compared to irbesartan, an established angiotensin receptor antagonist, as first line therapy in obese hypertensive patients.

Crossover to Half-Dose Photodynamic Therapy or Eplerenone in Chronic Central Serous Chorioretinopathy Patients

To compare the efficacy and safety of crossover treatment to half-dose photodynamic therapy (PDT) and eplerenone treatment after the failure of primary treatment in patients with chronic central serous chorioretinopathy (cCSC). Multicenter crossover clinical trial. At 3 months after the baseline visit of the SPECTRA (Half-Dose Photodynamic Therapy Versus Eplerenone: Treatment Trial for Chronic Central Serous Chorioretinopathy) randomized controlled trial, either half-dose PDT or eplerenone treatment was evaluated for each patient, and patients who still demonstrated subretinal fluid (SRF) were included in the current study, the SPECS (Central Serous Chorioretinopathy Treated with Half-Dose PDT or Eplerenone Crossover Study) trial. At the baseline visits for the current SPECS trial, crossover treatment was performed for patients who still demonstrated SRF. These patients received either half-dose PDT or oral eplerenone for 12 weeks. Both anatomic and functional parameters were evaluated 3 months after crossover treatment. Complete resolution of SRF on OCT. Forty-nine patients were included in the SPECS trial (38 received primary eplerenone treatment; 11 received half-dose PDT). At 3 months after crossover treatment, 32 of 37 (86.5%) in the crossover to half-dose PDT group and 2 of 9 (22.2%) in the crossover to eplerenone group had complete SRF resolution (P= 0.030). The mean foveal sensitivity increased significantly more in the crossover to half-dose PDT group (mean,+3.08 dB) compared with the crossover to eplerenone group (mean,-0.27 dB; P= 0.009). Patients with cCSC with the persistence of SRF after primary eplerenone treatment can benefit from half-dose PDT, which can induce a relatively fast and complete SRF resolution, along with an improvement in foveal sensitivity.

Short-term comparison between navigated subthreshold microsecond pulse laser and oral eplerenone for chronic central serous chorioretinopathy

To compare the anatomical/functional changes after navigated subthreshold pulse laser (SML) and oral eplerenone therapy for chronic central serous chorioretinopathy (cCSC). A total of 36 eyes of 36 patients suffering from cCSC treated with navigated SML (Navilas® 577s; OD-OS GmbH, near Berlin, Germany) (18 eyes, SML group) and oral eplerenone (18 eyes, eplerenone group) were enrolled in this retrospective study. Main outcome measures during a 3-month follow up period included changes of best corrected visual acuity (BCVA), central macular thickness (CMT), foveal subretinal fluid thickness (FSRFT), and subfoveal choroidal thickness (SFCT). At baseline average duration of symptoms was 6.8 ± 0.6 months in SML group and 6.4 ± 0.9 months in eplerenone group (p = 0.127). Mean BCVA, CMT and FSRFT changed significantly over time (p < 0.001). From baseline to 90 days the BCVA improved from 0.3 ± 0.1 to 0.1 ± 0.1 logMAR in SML group and from 0.3 ± 0. to 0.2 ± 0.1 logMAR in eplerenone group, CMT reduced from 357.1 ± 104.3 to 210.6 ± 46.7 μm and from 428.7 ± 107.7 to 332.5 ± 27.5 μm in SML group and eplerenone group respectively, FSRFT reduced from 144.4 ± 108.2 to 22.6 ± 37.2 μm and from 217.1 ± 105.9 to 54.4 ± 86.2 μm in SML group and eplerenone group. 55.6% of patients in SML group and 66.7% in eplerenone group showed a complete resolution of FSRFT during follow up. The interaction between group and time was statistically significant with greater absolute variation for CMT and FSRFT in SML group compared to eplerenone group (p < 0.001 and p = 0.043). SFCT did not change significantly during follow up (p = 0.083) for both groups. Both navigated SML and oral eplerenone were effective treatments showing recovery of retinal morphology and related visual acuity improvement in cCSC.

Effect of eplerenone on aldosterone and von Willebrand factor levelsin patients with myocardial infarction and chronic kidney disease

Aim: to study the levels of aldosterone and von Willebrand factor (VWF) in patients with Q-wave acute myocardial infarction (Q-AMI) and underling chronic kidney disease (CKD) using aldosterone antagonists. Materials and methods. The study group consisted of 106 patients with renal dysfunction who were hospitalized for acute Q-AMI. Serum levels of neurohumoral parameters (aldosterone and VWF) were determined in all the patients by enzyme-linked immunosorbent assay kits. Results. Reduction in the aldosterone levels was found in patients with Q-AMI and stage 2 CKD from 245.08 ± 17.38 pmol/l to 195.15 ± 13.82 pmol/l (P &lt; 0.05;) who received spironolactone and from 275.59 ± 23.43 to 169.37 ± 24.46 pmol/l (P &lt; 0.001) with eplerenone usage. Patients with stage 1 CKD showed a decreasing trend in aldosterone levels when using spironolactone (from 238.04 ± 20.37 pmol/l to 200.78 ± 9.15 pmol/l), and significantly decreased aldosterone levels when receiving eplerenone (from 229.77 ± 13.76 pmol/l to 156.76 ± 5.76 pmol/l; P &lt; 0.05). The serum concentration of VWF in stage 2 CKD patients was changed insignificantly on spironolactone therapy (from 0.99 ± 0.13 mg/l to 1.13 ± 0.06 mg/l) and it was significantly decreased in the eplerenone group – from 1.29 ± 0.19 mg/l to 0.71 ± 0.14 mg/l (P &lt; 0.05). In stage 1 CKD patients, the concentration of VWF was not decreased significantly with the use of spironolactone (from 1.22 ± 0.13 mg/l to 1.03 ± 0.06 mg/l), but it was decreased significantly when receiving eplerenone (from 1.14 ± 0.09 mg/l to 0.79 ± 0.08 mg/l; P &lt; 0.05). The data obtained indicate the significantly higher probability of declining both aldosterone (t = 2.91; P &lt; 0.01) and VWF (t = 2.59; P &lt; 0.01) with the use of eplerenone in the complex treatment as compared to the spironolactone administration. Conclusions. The effect of eplerenone to decrease the concentration of aldosterone and VWF is significantly greater than that of spironolactone, especially in AMI patients with stage 2 CKD.

Half-Dose Photodynamic Therapy Versus Eplerenone in Chronic Central Serous Chorioretinopathy (SPECTRA): A Randomized Controlled Trial

To compare the efficacy and safety between half-dose photodynamic therapy (PDT) and eplerenone therapy for treating chronic central serous chorioretinopathy (cCSC). This was a multicenter, open-label, randomized controlled trial. 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. 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. Half-dose PDT is superior to oral eplerenone for cCSC with respect to both short-term safety and efficacy outcomes.

Serum sodium and eplerenone use in patients with a myocardial infarction and left ventricular dysfunction or heart failure: insights from the EPHESUS trial.

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 < 135mmol/L or > 145mmol/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 141mmol/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.