eplerenone and Chronic-Disease

Chronic central serous chorioretinopathy (CSCR) is an ocular threatening disease, a common cause of central vision loss, affecting the posterior pole of the eye. Eplerenone (EPL) is a selective mineralocorticoid receptor antagonist that is primarily used to treat hypertension. Recently, it has shown many benefits in modifying the physio-pathological processes occurring upon stimulation of renin-angiotensin-aldosterone system at the ocular level. In CSCR treatment, several clinical studies and case reports prove the efficacy and safety of EPL. However, setbacks for such studies include a relatively small number of participants and short follow-up periods. This review article is intended to describe theories about the nature and classification of CSCR and recapitulate EPL therapeutic benefits as selective mineralocorticoid receptor antagonist in the treatment of CSCR. Furthermore, we survey the literature on clinical studies discussing the results of use of EPL in treatment of CSCR. In addition, EPL therapeutic formulations that have been developed are described, and future potential delivery systems will be suggested.

Topics: Central Serous Chorioretinopathy; Chronic Disease; Eplerenone; Humans; Mineralocorticoid Receptor Antagonists; Nanomedicine; Spironolactone

Tissue expansion and chronic inflammation in adipose tissue (AT) are closely related to nonalcoholic steatohepatitis (NASH) pathology. Angiogenesis is initiated by the detachment of pericytes (PCs) from vessels in AT. This process is necessary for the development of AT in obesity. The detachment is caused by excessive platelet-derived growth factor B (PDGF-B) derived from M1-macrophages (Mφ) infiltrating obese AT. On the other hand, AT of tamoxifen-induced systemic PDGF receptor-β knockout mice showed decreased detachment of PCs from vessels in obesity, thereby attenuating hypertrophy of AT mediated by neoangiogenesis, resulting in protection from the development of chronic AT inflammation and systemic insulin resistance. The selective mineralocorticoid receptor (MR) inhibitor eplerenone (Ep) suppresses chronic inflammation in fat and the liver, improves glucose and lipid metabolism, and inhibits body weight and fat mass gain in mice fed a high-fat diet. As a novel mechanism, Ep increases energy expenditure and suppresses fat accumulation, thereby controlling the polarity of visceral AT Mφ from inflammatory M1 to anti-inflammatory M2 dominant. In addition, Ep directly inhibits the activation of signals 1 and 2 of NLRP3-inflammasomes in Mφ, which is an inflammatory mechanism closely involved in the development of NASH. Thus, we propose novel therapeutic approaches to NASH. Inhibition of PDGF receptor-β signaling prevents AT hypertrophy by regulating AT angiogenesis, and MR inhibitors directly suppress chronic inflammation in the AT and liver.

Topics: Adipose Tissue; Animals; Chronic Disease; Eplerenone; Humans; Hypertrophy; Inflammasomes; Inflammation; Macrophages; Mice; Mice, Knockout; Mineralocorticoid Receptor Antagonists; Neovascularization, Pathologic; NLR Family, Pyrin Domain-Containing 3 Protein; Non-alcoholic Fatty Liver Disease; Proto-Oncogene Proteins c-sis; Receptors, Mineralocorticoid

Central serous chorioretinopathy (CSCR) is the second most common maculopathy after diabetic maculopathy between the third and fifth decades of life. CSCR is characterized by serous neurosensory retinal detachment occasionally coexisting with retinal pigment epithelium (RPE) detachment. CSCR usually has good clinical prognosis, often resolving spontaneously within the first three months. However, some patients may have recurrent episodes and chronic disease. CSCR can cause permanent visual loss due to persistent neurosensory retinal detachment and RPE atrophy, especially in chronic cases. In recent years, verteporfin-photodynamic therapy applied with standard and low-dose/low-fluence protocols, anti-vascular endothelial growth factors, glucocorticoid antagonists, mineralocorticoid receptor antagonists, and subthreshold micropulse laser with varying parameters have been investigated as treatment options. In this review, we evaluated randomized and non-randomized case series conducted after 2000 that included at least 3 patients with chronic CSCR over 3 months in duration who were treated with current treatment options for chronic CSCR.

Topics: Angiogenesis Inhibitors; Central Serous Chorioretinopathy; Chronic Disease; Eplerenone; Finasteride; Humans; Laser Therapy; Mineralocorticoid Receptor Antagonists; Photochemotherapy; Photosensitizing Agents; Vascular Endothelial Growth Factor A

Eplerenone is a selective mineralocorticoid receptor antagonist that has been recently included in the treatment of patients with chronic heart failure (CHF) and reduced systolic function. This brief review aims to summarize current evidence on the role of eplerenone in the therapy of patients with CHF. In the EPHESUS trial, 6632 post-myocardial infarction patients with ejection fraction (EF) <40% and clinical HF signs were randomized to eplerenone or placebo added to standard therapy 3 to 14 days after the event. After a 16 month follow-up period, eplerenone given early (<7 days) reduced the primary endpoints of all-cause mortality by 15% and cardiovascular death or cardiovascular hospitalization by 13%. In the subsequent EMPHASIS-HF trial, the efficacy and tolerability of eplerenone were tested in patients with mild CHF (NYHA functional class II) and EF ≤ 30% or between 30 and 35% with QRS duration >130 ms. After a median follow-up of 21 months eplerenone significantly reduced (by 37%) the primary composite outcome of risk of death from CV causes and first hospitalization for HF. Based on the above findings, the addition of eplerenone to standard therapy, at doses to be titrated from 25 to 50mg per day, is currently recommended in CHF patients with functional classes II to IV closely resembling those enrolled in these large clinical trials, with adequate monitoring for side effects (mainly hyperkalemia and renal failure). Whether the same beneficial effects of eplerenone extend to CHF patients with mild symptoms and no additional risk factors are unknown.

Topics: Chronic Disease; Eplerenone; Heart Failure; Humans; Mineralocorticoid Receptor Antagonists; Randomized Controlled Trials as Topic; Risk Factors; Spironolactone

Aldosterone antagonists (AldoAs) have been used to treat severe chronic heart failure (CHF). There is uncertainty regarding the efficacy of using AldoAs in mild to moderate CHF with New York Heart Association (NYHA) classifications of I to II. This study summarizes the evidence for the efficacy of spironolactone (SP), eplerenone (EP) and canrenone in mild to moderate CHF patients.. PubMed, MEDLINE, EMBASE and OVID databases were searched before June 2012 for randomized and quasi-randomized controlled trials assessing AldoA treatment in CHF patients with NYHA classes I to II. Data concerning the study's design, patients' characteristics and outcomes were extracted. Risk ratio (RR) and weighted mean differences (WMD) or standardized mean difference were calculated using either fixed or random effects models.. Eight trials involving 3929 CHF patients were included. AldoAs were superior to the control in all cause mortality (RR 0.79, 95% CI 0.66, 0.95) and in re-hospitalization for cardiac causes (RR 0.62, 95% CI 0.52, 0.74), the left ventricular ejection fraction was improved by AldoA treatment (WMD 2.94%, P = 0.52). Moreover, AldoA therapy decreased the left ventricular end-diastolic volume (WMD -14.04 ml, P < 0.00001), the left ventricular end-systolic volume (WMD -14.09 ml, P < 0.00001). A stratified analysis showed a statistical superiority in the benefits of SP over EP in reducing LVEDV and LVESV. AldoAs reduced B-type natriuretic peptide concentrations (WMD -37.76 pg ml(-1), P < 0.00001), increased serum creatinine (WMD 8.69 μmol l(-1), P = 0.0003) and occurrence of hyperkalaemia (RR 1.78, 95% CI 1.43, 2.23).. Additional use of AldoAs in CHF patients may decrease mortality and re-hospitalization for cardiac reasons, improve cardiac function and simultaneously ameliorate LV reverse remodelling.

Topics: Canrenone; Chronic Disease; Eplerenone; Heart Failure; Humans; Mineralocorticoid Receptor Antagonists; Randomized Controlled Trials as Topic; Severity of Illness Index; Spironolactone; Ventricular Remodeling

Topics: Aldosterone; Animals; Chronic Disease; Eplerenone; Humans; Kidney Diseases; Metabolic Syndrome; Mineralocorticoid Receptor Antagonists; Podocytes; Proteinuria; Receptors, Mineralocorticoid; Risk Factors; Spironolactone

Topics: Aldosterone; Chronic Disease; Contraindications; Eplerenone; Heart Failure; Humans; Mineralocorticoid Receptor Antagonists; Prognosis; Randomized Controlled Trials as Topic; Spironolactone; Survival Rate

Topics: Aldosterone; Chronic Disease; Death, Sudden, Cardiac; Diuretics; Eplerenone; Fibrosis; Heart Failure; Humans; Mineralocorticoid Receptor Antagonists; Myocardium; Randomized Controlled Trials as Topic; Spironolactone; Sulfonamides; Torsemide; Ventricular Remodeling

There has been a recent revival of interest in aldosterone receptor antagonists for the treatment of chronic heart failure. This was largely triggered by fresh insights into the role of aldosterone in a number of key pathophysiological processes, including fibrosis and remodeling, inflammation, and the potentiation of catecholamine effects. The therapeutic efficacy of spironolactone (Aldactone), Pfizer) in severe chronic heart failure was established by the Randomized Aldactone Evaluation Study, but hormonal side effects (gynecomastia) associated with the drug posed a problem. More recently, the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study has provided firm support for the use of eplerenone (Inspra, Pfizer) in heart failure following acute myocardial infarction in addition to neurohormonal blockade with angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers and beta-blockers. This strategy can be expected to benefit both mortality and morbidity. Due to the fact that eplerenone is a selective aldosterone receptor antagonist, it does not cause troublesome hormonal side effects. This is an important feature of the drug that is likely to help maintain compliance.

Topics: Aldosterone; Chronic Disease; Clinical Trials as Topic; Eplerenone; Heart Failure; Humans; Mineralocorticoid Receptor Antagonists; Myocardial Infarction; Spironolactone; Treatment Outcome

THE ROLE OF ALDOSTERONE: Aldosterone is the key hormone in salt-water homeostasis. In heart failure, it participates in the appearance and maintenance of signs of congestion. Predominantly synthesised in the glomerular area of the cortico-adrenal glands, extra adrenal production areas have recently been identified notably in the brain, the heart and the large artery trunks. Aldosterone is activated in the cells by the intracellular mineral corticoid receptor. IN CARDIOVASCULAR-PATHOLOGIES: In chronic heart failure, patients treated with conversion enzyme inhibitor may escape from the renin-angiotensin blockade and this may lead to increased aldosterone plasma levels. This increase can induce not only vascular lesions and myocardial fibrosis but also renal and cerebral lesions.. In patients with NYHA stage III or IV heart failure, addition of spironolactone to the treatment with conversion enzyme inhibitor, diuretic and/or digitalis leads to a reduction in morbidity and mortality, as demonstrated in the RALES study. The mechanisms by which spironolactone has a beneficial effect remain discussed.. The prescription of spironolactone is limited by hormonal side effects it provokes.. Eplerenone, a new competitive aldosterone receptor antagonist that appears to be devoid of such side effects and which, at least experimentally may well have the same beneficial effects, is presently under clinical assessment.

Topics: Adrenergic beta-Antagonists; Aldosterone; Angiotensin-Converting Enzyme Inhibitors; Chronic Disease; Diuretics; Eplerenone; Heart Failure; Homeostasis; Humans; Mineralocorticoid Receptor Antagonists; Multicenter Studies as Topic; Placebos; Randomized Controlled Trials as Topic; Receptors, Mineralocorticoid; Spironolactone; Time Factors

Comparing 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.. After 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.. Out 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).. Twelve 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.

Topics: Central Serous Chorioretinopathy; Chronic Disease; Eplerenone; Fluorescein Angiography; Follow-Up Studies; Humans; Photochemotherapy; Photosensitizing Agents; Tomography, Optical Coherence; Treatment Outcome; Visual Acuity

Heart failure remains one of the most prevalent clinical syndromes associated with significant morbidity and mortality. According to current guidelines, the prescription of a MRA is recommended to reduce the risk of HF hospitalization and death in all patients with symptomatic heart failure and no contraindications for this therapy.. The aim of our study was to determine the efficacy of eplerenone vs. spironolactone on left ventricular systolic function by measuring left ventricle ejection fraction (LVEF) in patients with chronic heart failure, especially their effect on preventing hospitalization, reducing mortality, and improving clinical status among patients with chronic HF.. From June 2021 to June 2022, the study was a randomized, prospective clinical trial single blind study. A total of 142 patients of chronic heart failure with reduced ejection fraction were selected by random sampling. Each patient was randomly allocated into either of the two groups and was continued receiving treatment with either spironolactone (Spiron-HF group) or eplerenone (Epler-HF group). Patients in Epler-HF group were compared with an arm of the same size and matched by age and gender patients in Spiron-HF group for management of chronic HFrEF. Each patient was evaluated clinically, biochemically, and echocardiographically at the beginning of treatment (baseline) after 6 months and at the end of 12th month. Echocardiography was performed to find out change in left ventricular systolic function.. After 12 months of treatment, significant improvement of left ventricular ejection fraction was observed in eplerenone treated arm (37.9 ± 3.8 ± 4.6 in Spiron-HF group versus 40.1 ± 5.7 in Epler-HF group; P < 0.05). A significant reduction in left ventricular end-systolic volume (6.3 ± 2.5ml in Spiron-HF versus 17.8± 4.4ml in Epler-HF group; P < 0.05) and left ventricular systolic diameter volume (2.7 ± 0.5ml in Spiron-HF versus 6.7 ± 0.2ml in Epler-HF group; P < 0.05), occurred after 12 months of treatment. Left ventricular global longitudinal strain (LV GLS) was significantly improved in Epler-HF group compared with Spiron-HF group (0.6 ± 0.4 versus 3.4 ± 0.9; P < 0.05). There were no significant differences observed in reduction of left ventricular end-diastolic volume (2.2 ± 0.5 ml versus 4.7 ± 1.1ml; P =0.103) and left ventricular diastolic diameter (1.2 ± 0.6 versus 1.7 ± 0.3; P=0.082) in both arms. The effects of both MRA agents spironolactone and eplerenone on the primary composite outcome, each of the individual mortality and hospital admission outcomes are shown in Figure 1 and 2. Patients of the Epler-HF group showed statistically significant lower cardiovascular mortality (HR 0.53; 95% CI 0.34-0.82; p= 0.007) and all-cause mortality (HR 0.64; 95% CI 0.44-0.93; p= 0.022) than patients of the Spiron-HF group. The statistical analysis did not show a statistically significant difference between Epler -HF and Spiron-HF study groups regarding the risk of the primary composite outcome; cardiovascular death or hospitalization due to HF (Hazard Ratio (HR) eplerenone vs. spironolactone = 0.95; 95% Confidence Interval (CI) 0.73- 1.27; p= 0.675).. Our study has demonstrated favorable effects of eplerenone on cardiac remodeling parameters and reduction of cardiovascular mortality and all-cause mortality compared with spironolactone in the treatment of HFrEF. The ability of eplerenone to effectively block the mineralocorticoid receptor while minimizing side effects and a significant reduction in the risk of hospitalization and cardiovascular death confirms its key role in the treatment of patients with chronic HFrEF.

Topics: Chronic Disease; Eplerenone; Heart Failure; Hospitalization; Humans; Mineralocorticoid Receptor Antagonists; Prospective Studies; Single-Blind Method; Spironolactone; Stroke Volume; Treatment Outcome; Ventricular Function, Left

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.

Topics: Central Serous Chorioretinopathy; Chronic Disease; Eplerenone; Fluorescein Angiography; Humans; Photochemotherapy; Photosensitizing Agents; Porphyrins; Quality of Life; Tomography, Optical Coherence; Treatment Outcome; Verteporfin; Visual Acuity

In chronic central serous chorioretinopathy (CSCR), fluid accumulates in the subretinal space. CSCR is a common visually disabling condition that develops in individuals up to 60 years of age, and there is no definitive treatment. Previous research suggests the mineralocorticoid receptor antagonist, eplerenone, is effective for treating CSCR; however, this drug is not licensed for the treatment of patients with CSCR. We aimed to evaluate whether eplerenone was superior to placebo in terms of improving visual acuity in patients with chronic CSCR.. This randomised, double-blind, parallel-group, multicentre placebo-controlled trial was done at 22 hospitals in the UK. Participants were eligible if they were aged 18-60 years and had had treatment-naive CSCR for 4 months or more. Patients were randomly assigned (1:1) to either the eplerenone or the placebo group by a trial statistician through a password-protected system online. Allocation was stratified by best-corrected visual acuity (BCVA) and hospital. Patients were given either oral eplerenone (25 mg/day for 1 week, increasing to 50 mg/day for up to 12 months) plus usual care or placebo plus usual care for up to 12 months. All participants, care teams, outcome assessors, pharmacists, and members of the trial management group were masked to the treatment allocation. The primary outcome was BCVA, measured as letters read, at 12 months. All outcomes apart from safety were analysed on a modified intention-to-treat basis (participants who withdrew consent without contributing a post-randomisation BCVA measurement were excluded from the primary analysis population and from most secondary analysis populations). The trial is registered with ISRCTN, ISRCTN92746680, and is completed.. Between Jan 11, 2017, and Feb 22, 2018, we enrolled and randomly assigned 114 patients to receive either eplerenone (n=57) or placebo (n=57). Three participants in the placebo group withdrew consent without contributing a post-randomisation BCVA measurement and were excluded from the primary outcome analysis population. All patients from the eplerenone group and 54 patients from the placebo group were included in the primary outcome. Modelled mean BCVA at 12 months was 79·5 letters (SD 4·5) in the placebo group and 80·4 letters (4·6) in the eplerenone group, with an adjusted estimated mean difference of 1·73 letters (95% CI -1·12 to 4·57; p=0·24) at 12 months. Hyperkalaemia occurred in eight (14%) patients in each group. No serious adverse events were reported in the eplerenone group and three unrelated serious adverse events were reported in the placebo group (myocardial infarction [anticipated], diverticulitis [unanticipated], and metabolic surgery [unanticipated]).. Eplerenone was not superior to placebo for improving BCVA in people with chronic CSCR after 12 months of treatment. Ophthalmologists who currently prescribe eplerenone for CSCR should discontinue this practice.. Efficacy and Mechanism Evaluation Programme, and National Institute for Health Research and Social Care.

Topics: Adult; Central Serous Chorioretinopathy; Chronic Disease; Double-Blind Method; Eplerenone; Female; Follow-Up Studies; Humans; Male; Medication Adherence; Middle Aged; Mineralocorticoid Receptor Antagonists; Treatment Outcome; Visual Acuity; Young Adult

To evaluate the safety and effects of oral eplerenone in chronic central serous chorioretinopathy.. Prospective, randomized, double-blind, placebo-control study at a tertiary referral academic private practice. For a diagnosis of chronic central serous chorioretinopathy, patients must have had at least 3 months clinical follow-up demonstrating persistent symptoms, subfoveal fluid on spectral-domain optical coherence tomography, and <50% reduction in fluid thickness. Patients were randomized 2:1 (treatment:placebo) to receive eplerenone (25 mg daily for 1 week, then up to 50 mg daily for 8 weeks) or placebo once daily.. Fifteen patients completed the study. Ten patients (15 eyes) were randomized into the eplerenone treatment arm, while the remaining 5 patients (6 eyes) received placebo. After 9 weeks of eplerenone therapy, mean logarithm of the minimal angle of resolution visual acuity improved from 0.394 (Snellen equivalent: 20/50) to 0.330 (20/43, P = 0.04). In the placebo group, the mean logarithm of the minimal angle of resolution visual acuity slightly decreased from 0.313 (20/41) to 0.342 (20/44) during the same period (P = 0.21). With respect to anatomic changes, mean maximal subretinal fluid height in the eplerenone group improved from 139.3 μm at baseline to 51.8 μm (P = 0.02), mean subfoveal fluid height improved from 121.4 μm to 29.4 μm (P = 0.01), and mean central subfield thickness improved from 366.2 μm to 283.7 μm (P = 0.02). In comparison with the placebo group, mean maximal subretinal fluid height worsened from 135.9 μm to 172.3 μm (P = 0.32), mean subfoveal fluid height worsened from 92.1 μm to 134.0 μm (P = 0.54), and mean central subfield thickness worsened from 345.0 μm to 380.0 μm (P = 0.37). No patients in either group experienced serious adverse events to result in treatment discontinuation.. These findings suggest that oral eplerenone therapy is safe and potentially effective in the treatment of chronic central serous chorioretinopathy with persistent subretinal fluid.

Topics: Administration, Oral; Adult; Aged; Central Serous Chorioretinopathy; Chronic Disease; Double-Blind Method; Eplerenone; Female; Humans; Male; Middle Aged; Mineralocorticoid Receptor Antagonists; Pilot Projects; Prospective Studies; Retina; Spironolactone; Subretinal Fluid; Visual Acuity

The mineralocorticoid receptor antagonist eplerenone improved clinical outcomes among patients with heart failure with reduced ejection faction (HFrEF) in the EMPHASIS-HF (Eplerenone in Mild Patients Hospitalization And SurvIval Study in Heart Failure) study. However, similar efficacy and safety have not been established in Japanese patients. We evaluated the efficacy and safety of eplerenone in patients with HFrEF in a multicenter, randomized, double-blind placebo-controlled outcome study (ClinicalTrials.gov Identifier: NCT01115855). The aim of the study was to evaluate efficacy predefined as consistency of the primary endpoint with that of EMPHASIS-HF at a point estimate of <1 for the hazard ratio.Methods and Results:HFrEF patients with NYHA functional class II-IV and an EF ≤35% received eplerenone (n=111) or placebo (n=110) on top of standard therapy for at least 12 months. The primary endpoint was a composite of death from cardiovascular causes or hospitalization for HF. The primary endpoint occurred in 29.7% of patients in the eplerenone group vs. 32.7% in the placebo group [hazard ratio=0.85 (95% CI: 0.53-1.36)]. Hospitalization for any cause and changes in plasma BNP and LVEF were favorable with eplerenone. A total of 17 patients (15.3%) in the eplerenone group and 10 patients (9.1%) in the placebo group died. Adverse events, including hyperkalemia, were similar between the groups.. Eplerenone was well-tolerated in Japanese patients with HFrEF and showed results consistent with those reported in the EMPHASIS-HF study.

Topics: Aged; Antihypertensive Agents; Chronic Disease; Double-Blind Method; Eplerenone; Female; Heart Failure; Hospitalization; Humans; Male; Middle Aged; Treatment Outcome

To evaluate the macular thickness, choroidal thickness, and visual acuity changes in eyes of patients with bilateral chronic central serous chorioretinopathy during eplerenone treatment.. This prospective clinical trial was conducted on patients with bilateral chronic central serous chorioretinopathy, who had subretinal fluid (SRF) in 1 eye. Twenty-eight patients were treated with 50 mg/day of oral eplerenone for 3 months and were observed for another 3 months. Twenty-eight eyes with SRF were compared with the 28 fellow eyes with pachychoroid pigment epitheliopathy.. The central macular and choroidal thickness showed a significant decrease (P < 0.005) at 3 months in all eyes, but change in choroidal thickness was smaller in nonexudative fellow eyes (P > 0.05 at 6 months). In the exudative eyes, the decrease in choroidal thickness showed a significant correlation with the resolution of SRF (P < 0.001). Visual acuity remained stable in all eyes, with significant improvement only in exudative eyes at 6 months (P < 0.005). Baseline choroidal thickness was a significant positive predictor for SRF decrease (P = 0.003).. Patients with chronic central serous chorioretinopathy can safely be treated with eplerenone as it can reverse choroidal vasodilation with an accompanying resolution of the SRF and improvement in visual acuity. These beneficial therapeutic effects are more pronounced in the exudative eyes.

Topics: Administration, Oral; Adult; Aged; Central Serous Chorioretinopathy; Choroid; Chronic Disease; Eplerenone; Exudates and Transudates; Female; Fluorescein Angiography; Follow-Up Studies; Fundus Oculi; Humans; Macula Lutea; Male; Middle Aged; Mineralocorticoid Receptor Antagonists; Prospective Studies; Spironolactone; Tomography, Optical Coherence; Treatment Outcome; Visual Acuity

To characterize eplerenone pharmacokinetics (PK) in Japanese chronic heart failure (CHF) patients and to estimate the impact of factors that may affect eplerenone PK, population pharmacokinetic (PPK) analysis was conducted. In addition, PK of Japanese CHF and Western CHF patients from a previous clinical pharmacology study were compared in the analysis. Eplerenone PK was characterized by a 1-compartment PPK model with first-order absorption and lag time in Japanese CHF patients. The population mean of apparent oral clearance (CL/F) in Japanese CHF patients was estimated as 5.31 L/h, which was similar to the mean CL/F for Western CHF patients. In the full model approach, creatinine clearance (CLcr) on CL/F and body weight on apparent central volume of distribution (Vc/F) were selected as factors that may affect PK. The effect of CLcr on CL/F predicted that CL/F would be decreased by 25% when CLcr was decreased from 80 mL/min to 50 mL/min. The effect of body weight on Vc/F predicted that Vc/F would be decreased by 18% when body weight was decreased from 80 kg to 60 kg. Distribution of individual CL/F estimates for Japanese CHF patients overlapped CL/F observed values for Western CHF patients, and CL/F values for Western CHF patients were contained within the distribution of CL/F estimates for Japanese CHF patients. No obvious difference between Japanese and Western subjects was detected even in the updated model by adding the data obtained from Western CHF patients and Western healthy adults to the model constructed with data from Japanese CHF patients.

Topics: Adult; Aged; Aged, 80 and over; Asian People; Chronic Disease; Double-Blind Method; Eplerenone; Female; Heart Failure; Humans; Male; Middle Aged; Mineralocorticoid Receptor Antagonists; Models, Biological; Spironolactone

Finerenone, a nonsteroidal mineralocorticoid receptor antagonist, was evaluated in Japanese patients with heart failure (HF) with reduced ejection fraction and chronic kidney disease and/or diabetes mellitus.. ARTS-HF Japan was a randomized, double-blind, phase 2b study. Patients (n=72) received oral, once-daily (o.d.) finerenone (2.5, 5, 7.5, 10 or 15 mg, up-titrated to 5, 10, 15, 20, or 20 mg, respectively, on day 30) or eplerenone (25 mg every other day, increased to 25 mg o.d. on day 30, and 50 mg on day 60) for 90 days. The primary endpoint was the proportion of individuals with a decrease of >30% in plasma NT-proBNP at day 90. Safety endpoints included the incidence of hyperkalemia. Decreases in NT-proBNP occurred in 23.1% of patients in the eplerenone group and 15.4%, 23.1%, 45.5%, 27.3% and 45.5% in the 2.5→5 mg, 5→10 mg, 7.5→15 mg, 10→20 mg and 15→20 mg finerenone groups, respectively (all P=NS). Mean changes in serum potassium levels were similar between groups.. Because of the small sample size, limited conclusions can be drawn. Considering the results of ARTS-HF and that finerenone was well tolerated in Japanese patients in ARTS-HF Japan, the safety and efficacy of finerenone should be further explored in a large outcomes trial including Japanese patients. (Circ J 2016; 80: 1113-1122).

Topics: Adult; Chronic Disease; Diabetes Mellitus; Double-Blind Method; Eplerenone; Heart Failure; Humans; Hyperkalemia; Japan; Naphthyridines; Natriuretic Peptide, Brain; Patient Safety; Peptide Fragments; Renal Insufficiency, Chronic; Spironolactone

To evaluate oral doses of the non-steroidal mineralocorticoid receptor antagonist finerenone given for 90 days in patients with worsening heart failure and reduced ejection fraction and chronic kidney disease and/or diabetes mellitus.. Miner Alocorticoid Receptor antagonist Tolerability Study-Heart Failure (ARTS-HF) was a randomized, double-blind, phase 2b multicentre study (ClinicalTrials.gov: NCT01807221). Of 1286 screened patients, 1066 were randomized. Patients received oral, once-daily finerenone (2.5, 5, 7.5, 10, or 15 mg, uptitrated to 5, 10, 15, 20, or 20 mg, respectively, on Day 30) or eplerenone (25 mg every other day, increased to 25 mg once daily on Day 30, and to 50 mg once daily on Day 60) for 90 days. The primary endpoint was the percentage of individuals with a decrease of >30% in plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) from baseline to Day 90. A key exploratory endpoint was a composite clinical endpoint of death from any cause, cardiovascular hospitalizations, or emergency presentation for worsening HF until Day 90. Mean age ranged from 69.2 to 72.5 years in different treatment groups (standard deviation 9.7-10.6 years). Decreases in NT-proBNP of >30% from baseline occurred in 37.2% of patients in the eplerenone group and 30.9, 32.5, 37.3, 38.8, and 34.2% in the 2.5→5, 5→10, 7.5→15, 10→20, and 15→20 mg finerenone groups, respectively (P = 0.42-0.88). Except for the 2.5→5 mg finerenone group, the composite clinical endpoint occurred numerically less frequently in finerenone-treated patients compared with eplerenone; this difference reached nominal statistical significance in the 10→20 mg group (hazard ratio 0.56, 95% confidence interval, CI, 0.35; 0.90; nominal P = 0.02), despite the fact that this phase 2 study was not designed to detect statistical significant differences. A potassium level increase to ≥5.6 mmol/L at any time point occurred in 4.3% of patients, with a balanced distribution among all treatment groups.. Finerenone was well tolerated and induced a 30% or greater decrease in NT-proBNP levels in a similar proportion of patients to eplerenone. The finding of reduced clinical events in the finerenone 10→20 mg group should be further explored in a large outcomes trial.

Topics: Aged; Chronic Disease; Diabetes Mellitus; Double-Blind Method; Eplerenone; Heart Failure; Humans; Mineralocorticoid Receptor Antagonists; Natriuretic Peptide, Brain; Peptide Fragments; Renal Insufficiency, Chronic; Spironolactone

Although inhibitors of the renin-angiotensin system are effective as first-line antihypertensive drugs in hypertensive patients with chronic kidney disease, they cannot completely prevent the progression of renal injury. Many animal studies, including our own, and a few human studies suggest that mineralocorticoid receptor blockade could inhibit the ongoing renal damage in chronic kidney disease. Thus, we designed this double-blinded, randomized, placebo-controlled trial to evaluate the antialbuminuric effect of a low dose (50 mg day(-1)) of the mineralocorticoid receptor antagonist eplerenone. The study subjects will include 340 hypertensive patients (blood pressure: 130-180/80-100 mm Hg) with albuminuria (urinary albumin/creatinine ratio: 30-600 mg g(-1) in the first morning void urine), who are treated with an inhibitor of the renin-angiotensin system. Other classes of antihypertensive drugs may be added as needed to achieve the target blood pressure (<130/80 mm Hg). The primary study end point is the change in the urinary albumin/creatinine ratio after a 1-year study period. This trial is expected to show whether a low dose of mineralocorticoid receptor antagonists can exert an antialbuminuric effect in patients with chronic kidney disease.

Topics: Adult; Aged; Albuminuria; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Blood Pressure; Chronic Disease; Creatine; Drug Therapy, Combination; Eplerenone; Female; Humans; Hypertension; Kidney; Kidney Diseases; Male; Middle Aged; Mineralocorticoid Receptor Antagonists; Sodium Chloride, Dietary; Spironolactone; Young Adult

In chronic heart failure (HF), aldosterone antagonists have been shown to improve survival in patients with low ejection fraction and moderate-to-severe symptoms [New York Heart Association (NYHA) classes III and IV]. Efficacy of these agents was also shown when they were administered to patients with left ventricular dysfunction and signs and symptoms of CHF early after acute myocardial infarction. It is not known whether the selective aldosterone antagonist eplerenone can improve outcomes in mildly symptomatic patients. The Eplerenone in Mild Patients Hospitalization And SurvIval Study in Heart Failure (EMPHASIS-HF) was designed to evaluate the effect of eplerenone on mortality and morbidity in patients with chronic systolic HF in NYHA class II. Methods Approximately 3100 patients with ejection fraction < or =30% and estimated glomerular filtration rate > or =30 mL/min/1.73 m(2) will be recruited. Patients are randomized 1:1 to double-blind eplerenone or placebo in addition to standard chronic HF therapy. Doses are adjusted from 25 mg every other day to 50 mg daily, depending on serum potassium. The primary endpoint is a composite of time to cardiovascular death or first hospital admission for worsening HF, whichever occurs first.. The study will be complete when approximately 813 subjects experience a primary endpoint. Clinical Trials.gov. NCT00232180.

Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Chronic Disease; Double-Blind Method; Eplerenone; Heart Failure, Systolic; Hospitalization; Humans; Mineralocorticoid Receptor Antagonists; Research Design; Spironolactone; Survival Analysis

To investigate choroidal vascularity index (CVI) changes after oral eplerenone treatment in chronic central serous chorioretinopathy (cCSC) using the Spectral-domain (SD)-Optical Coherence Tomography (OCT) with enhanced depth imaging (EDI) mode.. Thirty-six eyes of 18 patients suffering from cCSC with monolateral foveal subretinal fluid (FSRF) successfully treated with oral eplerenone treatment and 18 age-matched healthy subjects were enroled in this retrospective study. EDI-OCT images obtained using Heidelberg Spectralis OCT device in patients with cCSC and FSRF (group 1); fellow eye (group 2) or healthy patients (healthy) were exported and then imported into image analysis ImageJ software for subsequent quantitative analysis. The main outcome measures were luminal area (LA) and CVI.. A higher value of CVI was detected in group 1 compared to healthy eyes (p = 0.006). LA and CVI significantly reduced during follow up in group 1 and group 2. LA at 120 days was significantly lower compared to all previous time points both in group 1 and group 2 (p < 0.001). Median and [1st -3rd quartile] CVI values were 0.8 [0.7; 1.1] at baseline, 0.8 [0.7; 0.9] at 30 days; 0.7 [0.6; 0.9] at 60 and 90 days and 0.6 [0.5; 0.8] at 120 days in group 1 (p = 0.007) and 0.7 [0.6; 0.9] at baseline, 0.7 [0.7; 0.8] at 30 days; 0.7 [0.6; 0.7] at 60 and 90 days and 0.6 [0.6; 0.7] at 120 days in group 2 (p = 0.018).. Choroidal vascularity index reduced in cCSC patients after oral eplerenone treatment during follow up both in eyes with SRF and fellow eyes thus demonstrating the effectiveness of mineral corticoid receptor antagonists in recovering choroidal morphology.

Topics: Central Serous Chorioretinopathy; Choroid; Chronic Disease; Eplerenone; Humans; Retrospective Studies; Tomography, Optical Coherence

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.

Topics: Adult; Central Serous Chorioretinopathy; Chronic Disease; Eplerenone; Fluorescein Angiography; Humans; Middle Aged; Photochemotherapy; Photosensitizing Agents; Porphyrins; Retinal Vessels; Tomography, Optical Coherence

To study structural and functional outcomes of cystoid macular degeneration (CMD) in chronic central serous chorioretinopathy (CSCR).. 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.. 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 (. Treatment of eyes with CMD prevents further deterioration of vision. Round configuration of intra-retinal cystoid space has a better anatomical outcome.

Topics: Central Serous Chorioretinopathy; Chronic Disease; Eplerenone; Fluorescein Angiography; Humans; Macular Degeneration; Photochemotherapy; Retrospective Studies; Tomography, Optical Coherence; Visual Acuity

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.

Topics: Central Serous Chorioretinopathy; Chronic Disease; Eplerenone; Fluorescein Angiography; Humans; Lasers; Retina; Retrospective Studies; Tomography, Optical Coherence; Treatment Outcome

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.

Topics: Central Serous Chorioretinopathy; Chronic Disease; Cross-Over Studies; Eplerenone; Fluorescein Angiography; Humans; Photochemotherapy; Photosensitizing Agents; Tomography, Optical Coherence; Verteporfin; Visual Acuity

A previous report demonstrated efficacy of mineralocorticoid antagonist with adjuvant topical dexamethasone (MRA+DEX) in resolving subretinal fluid (SRF) in a chronic central serous chorioretinopathy (CSCR) patient. This pilot study investigates the use of MRA+DEX to treat recalcitrant, chronic CSCR patients.. Retrospective review of chronic, recalcitrant CSCR patients unresponsive to MRA alone who were treated with MRA+DEX and followed for up to 3 months. Apical SRF thickness and visual acuity were measured.. Ten eyes of eight chronic, recalcitrant patients were included with an average follow-up of 109 days. Mean percent reduction in apical fluid thickness at one month and at last follow-up after adding dexamethasone (DEX) was 33% and 52%, respectively. Five eyes (50%) achieved complete resolution of SRF. Three eyes (30%) showed partial response and two (20%) eyes had no response. There was no significant change in visual acuity.. MRA+DEX decreased SRF in some recalcitrant, chronic CSCR patients. Large prospective studies are needed to evaluate the utility of MRA+DEX in these chronic CSCR patients.

Topics: Central Serous Chorioretinopathy; Chronic Disease; Dexamethasone; Eplerenone; Fluorescein Angiography; Humans; Mineralocorticoid Receptor Antagonists; Pilot Projects; Retina; Retrospective Studies; Tomography, Optical Coherence

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.. 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.. 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 (. 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.

Topics: Administration, Oral; Central Serous Chorioretinopathy; Chronic Disease; Eplerenone; Fluorescein Angiography; Humans; Mineralocorticoid Receptor Antagonists; Retrospective Studies; Spironolactone; Tomography, Optical Coherence; Treatment Outcome; Visual Acuity

To compare the long-term outcomes in chronic central serous chorioretinopathy (cCSC) following half-fluence photodynamic therapy (HF-PDT) and oral eplerenone treatment.. This retrospective comparative study included consecutive patients of cCSC treated with either HF-PDT or eplerenone. The treatment outcomes of the two groups were analyzed at 3-month, 6-month, and 12-month post-treatment.. This study included 20 eyes (20 patients) in HF-PDT group, and 18 eyes (18 patients) in eplerenone group. All baseline parameters in HF-PDT and eplerenone groups were comparable including neurosensory detachment height (217.05 ± 140.25 µm vs 178.05 ± 164.24 µm respectively,. HF-PDT has a superior efficacy to achieve faster, greater and long-lasting resolution of subretinal fluid in cCSC compared to eplerenone therapy.

Topics: Central Serous Chorioretinopathy; Choroid; Chronic Disease; Eplerenone; Fluorescein Angiography; Humans; Photochemotherapy; Photosensitizing Agents; Porphyrins; Retrospective Studies; Tomography, Optical Coherence; Verteporfin; Visual Acuity

To investigate choroidal blood flow changes after isometric exercise in patients with chronic central serous chorioretinopathy nontreated or treated with mineralocorticoid receptor antagonists (MRA).. Foveolar choroidal laser Doppler flowmetry parameters - velocity (ChVel), volume (ChVol) and blood flow (ChBF) - of 22 eyes of 22 treated patients, 16 eyes of 16 untreated patients and 19 healthy controls were measured during a squatting test. Treatment consisted in MRA administration (eplerenone 50 mg/day or spironolactone 50 mg/day). The experiment comprised three successive periods: 30 seconds of rest, 2 min of continuous squatting exercise, and 150 seconds of recovery. Significance levels were calculated using a generalized estimating equation.. During the squatting period, nontreated CSCR eyes had a similar change in ChVel (p = 0.8), ChVol (p = 0.8), ChBF (p = 0.5) and resistance to healthy eyes. Treated CSCR eyes exhibited significantly smaller changes in ChVel (-0.1 ± 11%, p = 0.04) than healthy eyes (6 ± 8%). No significant difference was found for ChVol and ChBF between the groups. The increase in ChVol from baseline in the nontreated CSCR group (4.4 ± 9%) was lower than that of treated group (6.7%±11%; p = 0.01). Finally, ChBF and ChVel changes in the CSCR groups were not significantly different.. No abnormalities were detected in the changes in ChBF parameters during increased ocular perfusion pressure in nontreated CSCR patients compared with controls. MRA treatment in CSCR patients induced a significant reduction in ChBVel and an increase in ChBVol in response to isometric exercise, suggesting that MRA exerts effects on choroidal vascular changes.

Topics: Adult; Central Serous Chorioretinopathy; Choroid; Chronic Disease; Eplerenone; Exercise; Female; Follow-Up Studies; Humans; Laser-Doppler Flowmetry; Male; Middle Aged; Mineralocorticoid Receptor Antagonists; Prospective Studies; Regional Blood Flow; Tomography, Optical Coherence

To compare the macular morphology of good and poor responders to eplerenone treatment in chronic central serous chorioretinopathy (CSCR) patients. Thirty eyes of 29 patients with chronic CSCR were treated with 50 mg/day oral eplerenone and followed up for 1 year. The integrity of outer retinal layers at baseline was assessed using optical coherence tomography. Patients who showed complete resolution of subretinal fluid at 1 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). Ellipsoid zone interruption, ELM interruption and hyperreflective foci in outer segment (OS) and outer nuclear layer (ON layer) was significantly more frequent in Group 2 than in Group 1 (p < 0.05 for all parameteres). Outer segment elongation was significantly more frequently seen in Group 1 than in Group 2 (p < 0.05) Multivariable regression analysis showed that intact ellipsoid zone at baseline is an independent predictor of good therapeutic response, with an odds ratio of 26.00 (95% CI 3.69-183.45; p = 0.001) after controlling for the effect of hyperreflective foci and ELM integrity. 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 antagonist therapy in these patients.

Topics: Adult; Aged; Central Serous Chorioretinopathy; Chronic Disease; Eplerenone; Female; Follow-Up Studies; Forecasting; Humans; Male; Middle Aged; Mineralocorticoid Receptor Antagonists; Tomography, Optical Coherence; Treatment Outcome

The efficacy of mineralocorticoid receptor antagonist eplerenone to treat chronic central serous chorioretinopathy (CSCR) has been established. However, previous studies have been limited by small cohort size and short follow-up duration. This study aims to report 3-year clinical outcomes of patients treated with eplerenone for chronic CSCR.. Institutional review board-approved retrospective chart analysis at a single institution from 2012 to 2018. Baseline best-corrected visual acuity and anatomical measurements related to degree of subretinal fluid (SRF) were collected at eplerenone initiation. Follow-up data were collected at the closest date to 12, 24 and 36 months.. Data were obtained for 100 eyes of 83 patients at 1-year (mean 11.18 ± 4.00 months), 49 eyes at 2-year (24.01 ± 3.33 months) and 33 eyes at 3-year (mean 35.5 ± 7.89 months) follow-up visits. The rate of complete SRF resolution was 31%, 28% and 33%, respectively. At final follow-up, logarithm of the minimum angle of resolution visual acuity change from baseline was +0.10 ± 0.24 (p = 0.130). Average change from baseline at final follow-up for central subfield thickness was -97 ± 140.6 µm (p < 0.001), cube volume was -1.07 ± 1.71 mm. Anatomical improvement occurs primarily within the first year of eplerenone treatment for chronic CSCR.

Topics: Adult; Aged; Aged, 80 and over; Central Serous Chorioretinopathy; Chronic Disease; Eplerenone; Female; Humans; Macula Lutea; Male; Middle Aged; Mineralocorticoid Receptor Antagonists; Retrospective Studies; Visual Acuity

To assess the treatment response and predictive factors following eplerenone treatment in chronic central serous chorioretinopathy (CSCR).. A prospective, nonrandomized study involving fixed-dose eplerenone was conducted in 22 eyes of 11 consecutive patients with bilateral chronic CSCR. The changes in subretinal fluid (SRF), central macular thickness (CMT), and best-corrected visual acuity (BCVA) were analyzed.. A significant reduction in SRF was observed in 13 of 16 eyes with baseline SRF (81.25%) at 3 months (P < .04), with complete resolution in six eyes (37.5%) at 3 months and in 10 eyes (62.5%) at 6 months (P < .006). Baseline BCVA was a significant predictor of final BCVA (P < .001), whereas 3-month SRF height was a weak but significant predictor of the 6-month height (r. When treated with eplerenone, chronic CSCR shows a significant reduction in SRF, with baseline BCVA and 3-month SRF height being important predictive factors. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:479-486.].

Topics: Adult; Central Serous Chorioretinopathy; Chronic Disease; Eplerenone; Female; Fluorescein Angiography; Humans; Male; Middle Aged; Mineralocorticoid Receptor Antagonists; Pilot Projects; Prospective Studies; Retina; Subretinal Fluid; Tomography, Optical Coherence; Treatment Outcome; Visual Acuity

To evaluate the efficacy and safety of eplerenone for chronic nonresolving central serous chorioretinopathy (CSC).. Prospective, double-blind, randomized placebo-controlled study. Nineteen eyes of 17 patients with persistent subretinal fluid (SRF) due to CSC were enrolled and randomized to receive eplerenone 50 mg/day or placebo for 3 months, followed by a 3-month follow-up. The main outcome measure was change in SRF from baseline to 3 months of treatment. Secondary outcomes included change in SRF at any time-point, complete resolution of SRF, improvement in choroidal thickness and change in best-corrected visual acuity (BCVA).. Thirteen eyes were treated with eplerenone and six with placebo. Both groups showed reduction in SRF throughout the treatment period, with a significant reduction at months 1, 3 and 5 only in the treatment group. Twenty-three per cent in the treatment group and 30.8% per cent in the placebo group experienced complete resolution of SRF. A significant improvement in BCVA was noted in the placebo group at 4 months, as well as a significant difference in BCVA between groups at 3 months in favour of the placebo group (p = 0.005). There was no significant difference in choroidal thickness in either group throughout the study period. No adverse events related to eplerenone were noted in the treatment group.. In this study, eplerenone was not found to be superior to placebo in eyes with chronic CSC.

Topics: Administration, Oral; Adolescent; Adult; Aged; Central Serous Chorioretinopathy; Choroid; Chronic Disease; Dose-Response Relationship, Drug; Double-Blind Method; Eplerenone; Female; Fluorescein Angiography; Follow-Up Studies; Humans; Male; Middle Aged; Mineralocorticoid Receptor Antagonists; Prospective Studies; Spironolactone; Time Factors; Tomography, Optical Coherence; Treatment Outcome; Visual Acuity; Young Adult

To assess the effect of eplerenone on macular structure and function in patients with chronic central serous chorioretinopathy.. 17 eyes of 16 patients (aged 32-66 years) with chronic central serous chorioretinopathy treated at the Department of Ophthalmology and Ocular Oncology, Jagiellonian University in Cracow were enrolled. The duration of symptoms ranged between 4 and 24 months. The patients were dosed with eplerenone according to the scheme: first 25 mg/day for a week, then 50 mg/day for 3 months. The baseline examination and two follow-up visits (after 1-1,5 months and after 3-4 months respectively) involved best corrected visual acuity (Snellen, decimal scale), central retinal thickness in optical coherence tomography and visual disturbances in Amsler test.. The mean best corrected visual acuity improved from 0.61 (±0.25) to 0.67 (±0.28) and 0.72 (±0.28) at the first and second follow-up appointment, respectively. Central retinal thickness declined from 367 μm (±70) to 264 μm (±50) and 248 μm (±50) at the first and second follow up appointment, respectively (p<0.05). Amsler test findings improved in 10 eyes (58.8%), while the deterioration in central vision remained unchanged in 7 eyes (41.2%) at the first follow up appointment. During the second follow-up appointment, though, Amsler test improvement was reported in 7 eyes (50%), while the deterioration in central vision remained unchanged in 7 eyes (50%).. Our study suggests that eplerenone may provide an alternative treatment of chronic central serous chorioretinopathy, especially in patients with known contraindications to or ineligible for other treatments (for instance, retinal laser photocoagulation). Further randomized controlled trial is required.

Topics: Adult; Aged; Central Serous Chorioretinopathy; Choroid; Chronic Disease; Eplerenone; Female; Humans; Male; Middle Aged; Mineralocorticoid Receptor Antagonists; Retina; Spironolactone; Tomography, Optical Coherence; Treatment Outcome; Vision Tests

To evaluate the effect of eplerenone on patients with long-term recurring central serous chorioretinopathy (CSC).. In this retrospective case series, 11 patients with chronic recurring CSC were included. The main focus was to include patients who had undergone photodynamic therapy (4 patients), had undergone anti-vascular endothelial growth factor treatment (3 patients), or had several episodes of CSC in the past (4 patients) (mean age 60 years; SD 9.7, range 47-76).. Four patients (36.4%) had full resorption of neurosensory detachment under therapy of eplerenone with improvement of vision, while 4 more patients had improvement of vision despite residual edema. Eight patients (73%) had improved visual acuity (VA) at the end of eplerenone therapy, 2 patients had no change in VA, and 1 patient decreased VA. Mean time of treatment was 10.6 ± 9.9 weeks (range 3-38 weeks). All patients showed subretinal deposits, with 6 of them having hyperautofluorescent subretinal deposits.. Eplerenone represents a new treatment option for patients with CSC. Our data indicate a good response in those patients, leading to improvement of VA in 73% of patients.

Topics: Aged; Central Serous Chorioretinopathy; Chronic Disease; Eplerenone; Female; Fluorescein Angiography; Humans; Male; Middle Aged; Mineralocorticoid Receptor Antagonists; Photochemotherapy; Recurrence; Retrospective Studies; Spironolactone; Tomography, Optical Coherence; Visual Acuity

It is not known whether concomitant use of aspirin might attenuate the beneficial effects of mineralocorticoid receptor antagonists (MRAs). The purpose of this subgroup analysis was to explore the interaction between baseline aspirin treatment and the effect of eplerenone on the primary efficacy outcomes (composite of hospitalization for heart failure or cardiovascular mortality), its components, and safety markers [estimated glomerular filtration rate (eGFR), systolic blood pressure (SBP), and serum potassium >5.5 mmol/L] in the Eplerenone in Mild Patients Hospitalization and SurvIval Study in Heart Failure trial (EMPHASIS-HF).. Patients with chronic heart failure, reduced ejection fraction (HFREF), and mild symptoms were enrolled in EMPHASIS-HF. We evaluated baseline characteristics according to aspirin use. We explored the interaction between aspirin and eplerenone, using Cox proportional hazards models providing adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) and P-values for interaction. Of the 2737 patients randomized, 1605 patients (58.6%) were taking aspirin. The beneficial effects of eplerenone on the primary endpoint were similar in patients not treated (adjusted HR 0.59, 95% CI 0.46-0.75) or treated (adjusted HR 0.71, 95% CI 0.59-0.87) with aspirin at baseline (interaction P-value = 0.19). We did not observe any significant modification of the safety markers by aspirin that was clinically meaningful.. Aspirin use in patients with chronic systolic heart failure and mild symptoms did not substantially reduce the overall beneficial effects of the MRA eplerenone contrary to what has been described in some studies with ACE inhibitors.

Topics: Aged; Aspirin; Blood Pressure; Chronic Disease; Drug Interactions; Eplerenone; Female; Glomerular Filtration Rate; Heart Failure, Systolic; Humans; Male; Mineralocorticoid Receptor Antagonists; Platelet Aggregation Inhibitors; Potassium; Proportional Hazards Models; Spironolactone; Stroke Volume

Chronic central serous chorioretinopathy (CSC) is a vision-threatening eye disease for which there is still no approved treatment. Recent studies suggest that the corticosteroid pathway in the choroid is implicated in CSC pathogenesis, and that therapy with the aldosterone antagonist eplerenone improves clinical outcomes. However, there is still little clinical data to support this hypothesis. We performed a retrospective chart review to further investigate the clinical value of eplerenone treatment in patients with chronic CSC and to identify possible response predictors.. Twenty-four patients with chronic CSC resistant to conventional therapy over at least 4 months were included in this retrospective study. Patients were initially treated with 25 mg/day of eplerenone administered orally for 1 week, followed by a sustained daily dose of 50 mg. The primary outcome measure was percentage of eyes achieving complete resolution of subretinal fluid (SRF), recorded by spectral domain optical coherence tomography (SD-OCT). Secondary outcomes included changes in central macular thickness (CMT) and best-corrected visual acuity (BCVA). Baseline SD-OCT images were also evaluated as possible predictors of treatment response.. Twenty-nine percent of patients experienced complete resolution of SRF after a median of 106 days of treatment, while 33 % of patients showed a transient initial decrease in SRF, and 25 % failed to respond to treatment. Treatment had to be stopped in 13 % of patients because of adverse effects of the eplerenone treatment. In the study population, CMT decreased from 342 to 275 μm after treatment, which was associated with a modest improvement in mean BCVA from 0.35 to 0.3 logMar. The integrity of the ellipsoid zone and the retinal pigment epithelium (RPE) at baseline were associated with a tendency towards a favourable visual outcome.. This study confirms the proposed clinical value of eplerenone for treating patients with therapy-resistant CSC. However, patients presenting widespread RPE changes are less likely to benefit from eplerenone treatment, which may argue for an earlier intervention. Larger studies are needed to characterise patient subgroups that may benefit the most from eplerenone treatment.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Central Serous Chorioretinopathy; Chronic Disease; Dose-Response Relationship, Drug; Eplerenone; Female; Fluorescein Angiography; Follow-Up Studies; Fundus Oculi; Humans; Male; Middle Aged; Mineralocorticoid Receptor Antagonists; Retinal Pigment Epithelium; Retrospective Studies; Spironolactone; Tomography, Optical Coherence; Treatment Outcome; Visual Acuity

The objective of this study was to determine the cost-effectiveness of eplerenone compared with usual care in patients with chronic heart failure and New York Heart Association (NYHA) Class II symptoms.A Markov model was constructed with 5 health states to reflect NYHA symptom status (Classes I-IV) and death. All subjects began in the "Class II" health state and then moved to other symptom health states or died. Subjects could also be hospitalized for HF in any cycle. Transition probabilities were derived from the Eplerenone in Mild Patients Hospitalization And Survival Study in Heart Failure (EMPHASIS-HF) study. Decision analysis was applied to compare an Eplerenone Group with a Usual Care Group (UCG). In the UCG, 47.3% of subjects in Class II and 93.7% of subjects in Classes III and IV were assumed to be taking spironolactone (as per published data). In the Eplerenone Group, all subjects in Classes II, III, and IV were assumed to be taking eplerenone. The efficacy of spironolactone was assumed to be the same as eplerenone. Cost and utility data were derived from published sources. A discount rate of 5.0% was applied to future costs and benefits. The outcome of interest was incremental cost-effectiveness ratio (ICER) (cost per year of live saved (YoLS) and quality-adjusted life years (QALY) gained).Over 10 years the model predicted that for each patient compared with usual care, eplerenone would lead to 0.26 YoLS (discounted) and 0.19 QALYs gained (discounted), at a net cost of AUD $6961 (discounted). These equate to ICERs of AUD 28,001 per YoLS and AUD 37,452 per QALY gained. Sensitivity analyses indicated a 99.0% likelihood of eplerenone being cost-effective compared with usual care at a willingness to pay threshold of AUD 50,000 per QALY gained.From an Australian healthcare perspective, the addition of eplerenone in management of patients with chronic heart failure and NYHA Class II symptoms represents a cost-effective strategy compared with usual care.

Topics: Australia; Chronic Disease; Cost-Benefit Analysis; Eplerenone; Heart Failure; Hospitalization; Humans; Medication Therapy Management; Mineralocorticoid Receptor Antagonists; Severity of Illness Index; Spironolactone; Survival Analysis

To evaluate the efficacy of eplerenone, a mineralocorticoid receptor antagonist, in the treatment of chronic central serous chorioretinopathy (CSCR).. We conducted a retrospective study of 27 patients treated with eplerenone for chronic CSCR of at least 3 months duration. For each patient, visual acuity and macular OCT (central retinal thickness, height of foveal subretinal fluid (SRF), central choroidal thickness) were evaluated before treatment and at 1 month and 3 months. In the case of complete disappearance of SRF at 1 month, treatment was discontinued and follow-up was performed at 3 months.. Central retinal thickness was 371.6μm (266-573μm) before treatment. A clear decrease in retinal central thickness and height of SRF was observed at 1 month in 74% of patients (20 of 27 patients, central retinal thickness: 322.6μm at 1 month, P=0.01), with improvement of visual acuity in all of these patients. Follow-up at 3 months also found a decrease in SRF and central retinal thickness (294.3μm, P=0.002). Six patients had complete resolution of SRF at 1 month, without recurrence at 3 months. Six other patients had complete resolution of SRF at 3 months. No side effects requiring treatment discontinuation were observed.. In our study, eplerenone was associated with regression of central retinal thickness and height of SRF. Eplerenone appears to be a safe and effective treatment for chronic CSCR, with a probable mechanism of action on the pathophysiology of this disease.

Topics: Adult; Aged; Central Serous Chorioretinopathy; Chronic Disease; Eplerenone; Female; Humans; Male; Middle Aged; Mineralocorticoid Receptor Antagonists; Retrospective Studies; Spironolactone; Treatment Outcome; Young Adult

The fact that mineralocorticoid receptor antagonists reduce structural and functional alterations induced by cyclosporine A (CsA) indicates that aldosterone plays a key role in chronic CsA nephrotoxicity. We and other researchers have reported local renal aldosterone synthesis. To investigate local renal aldosterone's role in chronic CsA nephrotoxicity, we evaluated the effect of eplerenone (Epl) on renal structural damage and renal dysfunction in adrenalectomized (ADX) rats, and assessed whether the therapeutic benefit was associated with reduction of transforming growth factor-β1 (TGF-β1), connective tissue growth factor (CTGF), plasminogen activator inhibitor type 1 (PAI-1) and collagen I (COL-I) expression.. Male Sprague-Dawley rats fed a normal-sodium diet were divided in four groups: sham-ADX, ADX, CsA, or Epl. Rats in the ADX, CsA and Epl groups were adrenalectomized first. Aldosterone, sodium and potassium levels in serum and urine were measured on the second day. Two weeks later, vehicle (sham-ADX and ADX group), CsA (25mg/kg/d), or CsA and Epl (100 mg/ kg/d) combination was administrated, respectively. After six weeks, urinary protein, creatinine clearance (Ccr), tubulointerstitial fibrosis (TIF), aldosterone level in kidney, and renal aldosterone synthase CYP11B2, COL-I, TGF-β1, CTGF and PAI-1 gene expression levels were determined.. On the second day after surgery, adrenalectomized rats showed undetectable aldosterone with natriuresis, hyponatremia, decreased urinary potassium excretion and hyperpotassemia. CsA reduced Ccr, induced urinary proteins and up-regulated COL-I, TGF-β1, CTGF and PAI-1 gene expression with a significant development of TIF. Eplerenone administration prevented TIF and COL-I, TGF-β1 and PAI-1 up-regulation but did not improve renal function.. Our results suggest local renal aldosterone is an important mediator of renal injury induced by CsA.

Topics: Adrenalectomy; Aldosterone; Animals; Chronic Disease; Cyclosporine; Cytochrome P-450 CYP11B2; Disease Models, Animal; Electrolytes; Eplerenone; Fibrosis; Kidney; Kidney Diseases; Male; Potassium; Rats, Sprague-Dawley; RNA, Messenger; Sodium; Spironolactone

To evaluate the effect of oral eplerenone on subretinal fluid, visual acuity, and choroidal thickness in patients with chronic central serous chorioretinopathy (CSCR).. Retrospective review of all patients (14 eyes of 14 patients) monitored for a minimum of 3 months with chronic CSCR who were treated with oral eplerenone in a single multi-physician retina practice. Visual acuity, dilated funduscopic examination, and spectral-domain ocular coherence tomography (OCT) with enhanced depth imaging (EDI) were obtained at each visit. Measurement of subfoveal fluid (SFF) height and choroidal thickness were performed. Two-tailed paired t test was used to calculate statistical significance of pre- and post-treatment variables.. At 1 month, 10 of 14 eyes had decreased SFF height on OCT and two eyes had complete resolution of SFF. Mean SFF height decreased from 130 µm to 62 µm (P = .05). Mean choroidal thickness decreased from 315 µm to 282 µm (P = .07). Mean visual acuity improved from logMAR 0.41 to 0.40. At 3 months, 13 of 14 (93%) had decreased SFF on OCT, and nine eyes (64%) had complete resolution of SFF. Mean SFF height decreased to 21 µm (P = .004). Mean choroidal thickness decreased to 253 µm (P = .10). Mean visual acuity improved to logMAR 0.28 (P = .02).. Oral eplerenone may be effective in treating patients with chronic CSCR.

Topics: Administration, Oral; Adult; Aged; Central Serous Chorioretinopathy; Choroid; Chronic Disease; Eplerenone; Female; Humans; Male; Middle Aged; Mineralocorticoid Receptor Antagonists; Retrospective Studies; Spironolactone; Subretinal Fluid; Tomography, Optical Coherence; Visual Acuity

Topics: Chronic Disease; Eplerenone; Evidence-Based Medicine; Heart Failure, Systolic; Humans; Hyperkalemia; Mineralocorticoid Receptor Antagonists; Spironolactone

Chronic heart failure (CHF) remains an important cause of morbidity and mortality worldwide. Currently, there are no cost-effectiveness studies of eplerenone use in patients with New York Heart Association (NYHA) class II CHF.. We sought to evaluate the cost effectiveness of eplerenone compared with placebo in patients with chronic systolic heart failure and NYHA class II symptoms.. A 10-year Markov model with yearly cycles was constructed to evaluate the cost effectiveness of eplerenone compared with placebo, based on data from the EMPHASIS-HF (Eplerenone in Mild Patients Hospitalization And Survival Study in Heart Failure) study. The model classified subjects into two health states: 'Alive with CHF' and 'Dead'. Information about the cost of disease was derived from Australian Refined Diagnosis-Related Groups (AR-DRG) data. The cost of eplerenone was taken from the Australian Pharmaceutical Benefit Scheme. Utility data were derived from published sources, and a 5 % annual discount rate was applied to future costs and benefits. Over 10 years, and compared with placebo, the model predicted that eplerenone would lead to a saving of 0.5 life-years (discounted) and 0.4 quality-adjusted life-years (QALYs) per person. The net cost was (in Australian dollars [$A]) $A6,117 (discounted) per person. These equated to incremental cost-effectiveness ratios of $A12,024 per life-year saved and $A16,700 per QALY saved. Sensitivity analyses indicated that these results were robust.. Eplerenone may represent a cost-effective strategy for preventing morbidity and mortality among patients with chronic systolic heart failure and NYHA class II symptoms.

Topics: Age Factors; Aged; Australia; Chronic Disease; Cost-Benefit Analysis; Eplerenone; Female; Heart Failure, Systolic; Humans; Male; Markov Chains; Middle Aged; Mineralocorticoid Receptor Antagonists; Models, Economic; Quality-Adjusted Life Years; Racial Groups; Sex Factors; Spironolactone

Topics: Administration, Oral; Adult; Central Serous Chorioretinopathy; Chronic Disease; Eplerenone; Female; Humans; Male; Middle Aged; Mineralocorticoid Receptor Antagonists; Receptors, Mineralocorticoid; Spironolactone; Subretinal Fluid; Tomography, Optical Coherence; Treatment Outcome; Visual Acuity

Patients with chronic diseases often receive multiple medications and are associated with increased vulnerability to medication errors. Identifying high-alert medications for them would help to prioritize the interventions with greatest impact for improving medication safety. The aim of this study was to develop a list of high-alert medications for patients with chronic illnesses (HAMC list) that would prove useful to the Spanish National Health Service strategies on chronicity.. The RAND/UCLA appropriateness method was used. Drug classes/drugs candidates to be included on the HAMC list were identified from a literature search in MedLine, bulletins issued by patient safety organizations, incidents recorded in Spanish incident reporting systems, and previous lists. Eighteen experts in patient/medication safety or in chronic diseases scored candidate drugs for appropriateness according to three criteria (evidence, benefit and feasibility of implementing safety practices). Additionally they rated their priority of inclusion on a Likert scale.. The final HAMC list includes 14 drug classes (oral anticoagulants, narrow therapeutic range antiepileptics, antiplatelets - including aspirin -, antipsychotics, β-blockers, benzodiazepines and analogues, corticosteroids long-term use, oral cytostatics, oral hypoglycemic drugs, immunosuppressants, insulins, loop diuretics, nonsteroidal anti-inflammatory drugs, and opioid analgesics), and 4 drugs or pairs of drugs (amiodarone/ dronedarone, digoxin, oral methotrexate and spironolactone/eplerenone).. An initial list of high-alert medications for patients with chronic diseases has been developed, which can be built into the medication management strategies for chronicity to guide the implementation of efficient safety strategies and to identify those patients at greater risk for preventable adverse drug events.

Topics: Adrenal Cortex Hormones; Adrenergic beta-Antagonists; Amiodarone; Analgesics, Opioid; Anti-Arrhythmia Agents; Anti-Inflammatory Agents, Non-Steroidal; Anticonvulsants; Antipsychotic Agents; Benzodiazepines; Chronic Disease; Cytostatic Agents; Digoxin; Dronedarone; Drug-Related Side Effects and Adverse Reactions; Eplerenone; Humans; Hypoglycemic Agents; Immunosuppressive Agents; Insulin; Methotrexate; Mineralocorticoid Receptor Antagonists; Platelet Aggregation Inhibitors; Sodium Potassium Chloride Symporter Inhibitors; Spironolactone

Still no randomised controlled trials versus spironolactone, but a prematurely terminated placebo-controlled trial with 2737 patients.

Topics: Chronic Disease; Clinical Trials as Topic; Eplerenone; Heart Failure; Humans; Hyperkalemia; Mineralocorticoid Receptor Antagonists; Spironolactone

Topics: Chronic Disease; Eplerenone; Heart Failure; Humans; Mineralocorticoid Receptor Antagonists; Spironolactone

Hypertension is a major risk factor for the development and progression of chronic kidney disease (CKD). Mineralocorticoid receptor antagonists (MRAs) are effective in the management of resistant hypertension but are not widely used in CKD because of the risk of hyperkalemia. We retrospectively evaluated the long-term effects and safety of MRAs added to a pre-existing antihypertensive regimen in subjects with resistant hypertension associated with stage 3 CKD. In all, 32 patients were treated with spironolactone and 4 with eplerenone for a median follow-up of 312 days. MRAs induced a significant decrease in systolic blood pressure from 162±22 to 138±14 mm Hg (P<0.0001) and in diastolic blood pressure from 87±17 to 74±12 mm Hg (P<0.0001). Serum potassium increased from 4.0±0.5 to 4.4±0.5 mEq l(-1) (P=0.0001), with the highest value being 5.8 mEq l(-1). The serum creatinine increased from 1.5±0.3 to 1.8±0.5 mg dl(-1) (P=0.0004) and the estimated glomerular filtration rate decreased from 48.6±8.7 to 41.2±11.5 ml min(-1) per 1.73 m(2) (P=0.0002). One case of acute renal failure and three cases of significant hyperkalemia occurred. MRAs significantly reduced blood pressure in subjects with resistant hypertension associated with stage 3 CKD, although close biochemical monitoring is recommended because of an increased risk of hyperkalemia and worsening of renal function.

Topics: Acute Kidney Injury; Aged; Alabama; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Biomarkers; Blood Pressure; Chi-Square Distribution; Chronic Disease; Creatinine; Diuretics; Drug Resistance; Drug Therapy, Combination; Eplerenone; Female; Glomerular Filtration Rate; Humans; Hyperkalemia; Hypertension; Kidney; Kidney Diseases; Logistic Models; Male; Middle Aged; Mineralocorticoid Receptor Antagonists; Potassium; Retrospective Studies; Risk Assessment; Risk Factors; Spironolactone; Time Factors; Treatment Outcome

We investigated the effects of chronic mineralocorticoid receptor blockade with eplerenone on the development and progression of hypertension and end organ damage in Dahl salt-sensitive rats. Eplerenone significantly attenuated the progressive rise in systolic blood pressure (SBP) (204 ± 3 vs. 179±3 mmHg, p < 0.05), reduced proteinuria (605.5 ± 29.6 vs. 479.7 ± 26.1 mg/24h, p < 0.05), improved injury scores of glomeruli, tubules, renal interstitium, and vasculature in Dahl salt-sensitive rats fed a high-salt diet. These results demonstrate that mineralocorticoid receptor antagonism provides target organ protection and attenuates the development of elevated blood pressure (BP) in a model of salt-sensitive hypertension.

Topics: Aldosterone; Animals; Blood Pressure; Chronic Disease; Creatinine; Disease Models, Animal; Disease Progression; Electrolytes; Eplerenone; Heart Rate; Hypertension, Renal; Kidney; Male; Mineralocorticoid Receptor Antagonists; Organ Size; Rats; Rats, Inbred Dahl; Receptors, Mineralocorticoid; Sodium Chloride, Dietary; Spironolactone

Topics: Adult; Aged; Aged, 80 and over; Chronic Disease; Clinical Trials as Topic; Eplerenone; Female; Humans; Hyperkalemia; Hypertension; Kidney Diseases; Male; Middle Aged; Spironolactone; Young Adult

Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Cardiac Output, Low; Chronic Disease; Death, Sudden, Cardiac; Drug Therapy, Combination; Eplerenone; Humans; Mineralocorticoid Receptor Antagonists; Myocardial Infarction; Renin-Angiotensin System; Spironolactone; Treatment Outcome

Although aldosterone, acting via mineralocorticoid receptors, causes left ventricular (LV) hypertrophy in experimental models of high-aldosterone hypertension, little is known about the role of aldosterone or mineralocorticoid receptors in mediating adverse remodeling in response to chronic pressure overload.. We used the mineralocorticoid receptor-selective antagonist eplerenone (EPL) to test the role of mineralocorticoid receptors in mediating the transition from hypertrophy to failure in mice with chronic pressure overload caused by ascending aortic constriction (AAC). One week after AAC, mice were randomized to regular chow or chow containing EPL (200 mg/kg per day) for an additional 7 weeks. EPL had no significant effect on systolic blood pressure after AAC. Eight weeks after AAC, EPL treatment improved survival (94% versus 65%), attenuated the increases in LV end-diastolic (3.4+/-0.1 versus 3.7+/-0.1 mm) and end-systolic (2.0+/-0.1 versus 2.5+/-0.2 mm) dimensions, and ameliorated the decrease in fractional shortening (42+/-2% versus 34+/-4%). EPL also decreased myocardial fibrosis, myocyte apoptosis, and the ratio of matrix metalloproteinase-2/tissue inhibitor of matrix metalloproteinase-2. These beneficial effects of EPL were associated with less myocardial oxidative stress, as assessed by 3-nitrotyrosine staining, reduced expression of the adhesion molecule intercellular adhesion molecule-1, and reduced infiltration by macrophages.. Mineralocorticoid receptors play an important role in mediating the transition from LV hypertrophy to failure with chronic pressure overload. The effects of mineralocorticoid receptor stimulation are associated with alterations in the interstitial matrix and myocyte apoptosis and may be mediated, at least in part, by oxidative stress and inflammation.

Topics: Animals; Aorta; Apoptosis; Blood Pressure; Cell Size; Chronic Disease; Constriction, Pathologic; Drug Evaluation, Preclinical; Eplerenone; Fibrosis; Heart Failure; Hypertrophy, Left Ventricular; Intercellular Adhesion Molecule-1; Ligation; Male; Matrix Metalloproteinases; Mice; Mineralocorticoid Receptor Antagonists; Myocarditis; Myocardium; Myocytes, Cardiac; Oxidative Stress; Pressure; Random Allocation; Receptors, Mineralocorticoid; Spironolactone; Tissue Inhibitor of Metalloproteinase-1; Tissue Inhibitor of Metalloproteinase-2; Tyrosine

In heart failure (HF), aldosterone has been implicated in the formation of reactive interstitial fibrosis, a maladaptation that contributes to left ventricular (LV) remodeling. Eplerenone is a novel selective aldosterone blocker. The present study examined the effects of long-term monotherapy with eplerenone on the progression of LV dysfunction and remodeling in dogs with chronic HF.. HF was produced in 14 dogs by intracoronary microembolizations that were discontinued when LV ejection fraction (EF) was between 30% and 40%. Two weeks after the last embolization, dogs were randomized to 3 months of oral therapy with eplerenone (10 mg/kg twice daily, n=7) or no therapy at all (control, n=7). Hemodynamic measurements were made just before randomization and were repeated at the end of 3 months of therapy. In control dogs, LV end-diastolic and end-systolic volume increased significantly (62+/-4 versus 68+/-4 mL, P<0.001, and 38+/-3 versus 47+/-3 mL, P<0.001, respectively), and EF decreased significantly (38+/-1% versus 31+/-2%, P<0.001). In contrast, end-diastolic volume, end-systolic volume, and EF remained unchanged during the 3 months of treatment in eplerenone-treated dogs. LV end-diastolic wall stress increased significantly in control dogs but decreased significantly in eplerenone-treated dogs. Compared with control, eplerenone was associated with a 28% reduction in cardiomyocyte cross-sectional area, a 37% reduction of volume fraction of reactive interstitial fibrosis, and a 34% reduction of volume fraction of replacement fibrosis.. Our results indicate that long-term therapy with eplerenone prevents progressive LV dysfunction and attenuates LV remodeling in dogs with chronic HF.

Topics: Administration, Oral; Animals; Chronic Disease; Disease Models, Animal; Disease Progression; Dogs; Echocardiography; Enzyme Activation; Eplerenone; Fibroblast Growth Factor 2; Heart; Heart Failure; Hemodynamics; Mineralocorticoid Receptor Antagonists; Myocardium; RNA, Messenger; Spironolactone; Stroke Volume; Treatment Outcome; Ventricular Dysfunction, Left; Ventricular Remodeling