Effects of the mineralocorticoid receptor antagonist eplerenone in experimental autoimmune encephalomyelitis.

There is growing evidence indicating that mineralocorticoid receptor (MR) expression influences a wide variety of functions in metabolic and immune response. The present study explored if antagonism of the MR reduces neuroinflammation in the spinal cord of mice with experimental autoimmune encephalomyelitis (EAE). Eplerenone (EPLE) (100 mg/kg dissolved in 30% 2-hydroxypropyl-ß-cyclodextrin) was administered intraperitoneally (i.p.) daily from EAE induction (day 0) until sacrificed on day 17 post-induction. The MR blocker (a) significantly decreased the inflammatory parameters TLR4, MYD88, IL-1ß, and iNOS mRNAs; (b) attenuated HMGB1, NLRP3, TGF-ß mRNAs, microglia, and aquaporin4 immunoreaction without modifying GFAP. Serum IL-1ß was also decreased in the EAE+EPLE group. Moreover, EPLE treatment prevented demyelination and improved clinical signs of EAE mice. Interestingly, MR was decreased and GR remained unchanged in EAE mice while EPLE treatment restored MR expression, suggesting that a dysbalanced MR/GR was associated with the development of neuroinflammation. Our results indicated that MR blockage with EPLE attenuated inflammation-related spinal cord pathology in the EAE mouse model of Multiple Sclerosis, supporting a novel therapeutic approach for immune-related diseases.

Glomerular and tubular effects of dapagliflozin, eplerenone and their combination in patients with chronic kidney disease: A post-hoc analysis of the ROTATE-3 study.

AIM: Sodium-glucose co-transporter 2 inhibitors and mineralocorticoid receptor antagonists reduce albuminuria and the risk of kidney failure. The aim of this study was to investigate the effects of both agents alone and in combination on markers of the glomerular endothelial glycocalyx and tubular function. METHODS: This post-hoc analysis utilized data of the ROTATE-3 study, a randomized cross-over study in 46 adults with chronic kidney disease and urinary albumin excretion ≥100 mg/24 h, who were treated for 4 weeks with dapagliflozin, eplerenone or its combination. The effects of dapagliflozin, eplerenone and the combination on outcome measures such as heparan sulphate, neuro-hormonal markers and tubular sodium handling were assessed with mixed repeated measures models. RESULTS: The mean percentage change from baseline in heparan sulphate after 4 weeks treatment with dapagliflozin, eplerenone or dapagliflozin-eplerenone was -34.8% (95% CI -52.2, -10.9), -5.9% (95% CI -32.5, 31.3) and -28.1% (95% CI -48.4, 0.1) respectively. The mean percentage change from baseline in plasma aldosterone was larger with eplerenone [38.9% (95% CI 2.8, 87.7)] and dapagliflozin-eplerenone [32.2% (95% CI -1.5, 77.4)], compared with dapagliflozin [-12.5% (95% CI -35.0, 17.8)], respectively. Mean percentage change from baseline in copeptin with dapagliflozin, eplerenone or dapagliflozin-eplerenone was 28.4% (95% CI 10.7, 49.0), 4.2% (95% CI -10.6, 21.4) and 23.8% (95% CI 6.6, 43.9) respectively. Dapagliflozin decreased proximal absolute sodium reabsorption rate by 455.9 mmol/min (95% CI -879.2, -32.6), while eplerenone decreased distal absolute sodium reabsorption rate by 523.1 mmol/min (95% CI -926.1, -120.0). Dapagliflozin-eplerenone decreased proximal absolute sodium reabsorption [-971.0 mmol/min (95% CI -1411.0, -531.0)], but did not affect distal absolute sodium reabsorption [-9.2 mmol/min (95% CI -402.0, 383.6)]. CONCLUSIONS: Dapagliflozin and eplerenone exert different effects on markers of glomerular and tubular function supporting the hypothesis that different mechanistic pathways may account for their kidney protective effects.

Mineralocorticoid Receptor Antagonism by Eplerenone and Arterial Inflammation in HIV: The MIRABELLA HIV Study.

Importance: The risk for atherosclerotic disease is increased 1.5- to 2.0-fold among persons with HIV (PWH). Increased activation of the renin-angiotensin-aldosterone system may contribute to increased arterial inflammation in this population. Objective: To determine the effects of eplerenone on arterial inflammation among well-treated PWH without known cardiovascular disease (CVD). Design, Setting, and Participants: Well-treated PWH who participated in the double-blinded, placebo-controlled, Mineralocorticoid Receptor Antagonism for Cardiovascular Health in HIV (MIRACLE HIV) study between February 2017 and March 2022 assessing the effects of eplerenone on myocardial perfusion were invited to participate in the Mineralocorticoid Receptor Antagonism By Eplerenone to Lower Arterial Inflammation in HIV (MIRABELLA) substudy if there was no current statin use. Participants were enrolled in the MIRABELLA study and underwent additional 18F-fludeoxyglucose-positron emission tomography/computed tomography (18F-FDG PET/CT) imaging of the aorta and carotid arteries to assess arterial inflammation over 12 months of treatment with eplerenone vs placebo. Interventions: Eplerenone, 50 mg, twice a day vs identical placebo. Main Outcomes and Measures: The primary outcome was change in target to background ratio (TBR), a measure of arterial wall inflammation, in the index vessel after 12 months of treatment. The index vessel was defined as the vessel (aorta, left carotid artery, or right carotid artery) with the highest TBR at baseline in each participant. Results: A total of 26 participants (mean [SD] age, 54 [7] years; 18 male [69%]) were enrolled in the study. Treatment groups (eplerenone, 13 vs placebo, 13) were of similar age, sex, and body mass index. Eplerenone was associated with a reduction in TBR of the primary end point, the index vessel (eplerenone vs placebo: model treatment effect, -0.31; 95% CI, -0.50 to -0.11; P = .006; percentage change, -12.4% [IQR, -21.9% to -2.6%] vs 5.1% [IQR, -1.6% to 11.0%]; P = .003). We further observed a significant reduction of the TBR of the most diseased segment (MDS) of the index vessel (eplerenone vs placebo: -19.1% [IQR, -27.0% to -11.9%] vs 6.8% [IQR, -9.1% to 12.1%]; P = .007). A similar result was seen assessing the index vessel of the carotids (eplerenone vs placebo: -10.0% [IQR, -21.8% to 3.6%] vs 9.7% [IQR, -9.8% to 15.9%]; P = .046). Reduction in the TBR of MDS of the index vessel on 18F-FDG PET/CT correlated with improvement in the stress myocardial blood flow on cardiac magnetic resonance imaging (Spearman ρ = -0.67; P = .01). Conclusion and Relevance: In this small randomized clinical trial, eplerenone was associated with reduction in arterial inflammation among well-treated PWH without known CVD. In addition, reductions in arterial inflammation as measured by 18F-FDG PET/CT were related to improvements in stress myocardial perfusion. Further larger studies should explore whether eplerenone is a potential treatment strategy for inflammatory-mediated CVD in PWH. Trial Registration: ClinicalTrials.gov Identifier: NCT02740179.

Unilateral adrenalectomy for a drug-resistant bilateral primary aldosteronism with heart failure: pathophysiology and surgical indication.

BACKGROUND: Patients with bilateral primary aldosteronism (PA) generally are treated with antihypertensive drugs, but optimal treatment for patients with complications due to refractory hypertension has not been established. In this report, we present a case with bilateral PA who presented with persistent hypertension, despite treatment with 6 drugs, and left-dominant heart failure, which was improved after unilateral adrenalectomy. CASE PRESENTATION: A 61-year-old man was admitted to our hospital because of severe left-dominant heart failure. His heart rhythm was atrial fibrillation and the left ventricle was diffusely hypertrophic and hypokinetic. Coronary arteries were normal on coronary arteriogram. Primary aldosteronism was suspected based on severe hypokalemia (2.5 mEq/L) and plasma aldosterone concentration (PAC; 1,410 pg/mL). Although computed tomography (CT) showed a single left cortical nodule, adrenal vein sampling (AVS) indicated bilateral PA. Early in the case, heart failure and hyperkalemia in this patient were improved by treatment with a combination of 6 antihypertensive drugs (spironolactone 25 mg/day, eplerenone 100 mg/day, azosemide 60 mg/day, tolvaptan 7.5 mg/day, enalapril 5 mg/day, and bisoprolol fumarate 10 mg/day); however, heart failure relapsed after four months of treatment. We hypothesized that hypertension caused by excess aldosterone was inducing the patient's heart failure. In order to reduce aldosterone secretory tissue, a laparoscopic adrenalectomy was performed for the left adrenal gland, given the higher level of aldosterone from the left gland compared to the right. Following surgery, the patient's heart failure was successfully controlled despite the persistence of high PAC. Treatment with anti-hypertensive medications was reduced to two drugs (eplerenone 100 mg/day and bisoprolol fumarate 10 mg/day). In order to elucidate the mechanism of drug resistance, immunohistochemistry (IHC) and real time-polymerase chain reaction (RT-PCR) assays were performed to assess the expression of steroidogenic factor 1 (SF-1), a regulator of steroid synthesis in adrenal tissue. IHC and RT-PCR demonstrated that the expression of SF-1 in this patient (at both the protein and mRNA levels) was higher than that observed in unilateral PA cases that showed good responsivity to drug treatment. CONCLUSIONS: Unilateral adrenalectomy to reduce aldosterone secretory tissue may be useful for patients with drug-refractory, bilateral PA. Elevated expression of SF-1 may be involved in drug resistance in PA.

Agoraphobia and panic attacks complicated by primary aldosteronism improved by treatment with eplerenone: a case report.

BACKGROUND: Primary aldosteronism (PA) is an adrenal gland disease, that induces increased secretion of the mineralocorticoid, aldosterone, resulting in symptoms such as hypertension. This study reports a patient with agoraphobia and panic attacks, associated with PA. This patient's psychiatric symptoms improved after treatment with eplerenone, a mineralocorticoid receptor antagonist. CASE PRESENTATION: The patient was a 40-year-old female with agoraphobia, which refers to the irrational fear of situations that may cause anxiety, and panic attacks characterized by profuse sweating, palpitations, and generalized weakness. She was diagnosed with hypertension from PA. Subsequently, she received treatment with eplerenone, which improved her agoraphobia and panic attacks. CONCLUSIONS: There have been no previous reports on PA associated with agoraphobia and panic attacks that improved with pharmacotherapy. Patients with agoraphobia and panic attacks should be evaluated for PA. In patients with PA, pharmacotherapy with eplerenone should be considered.

Underutilization of Mineralocorticoid Antagonists in Patients With Heart Failure With Reduced Ejection Fraction.

BACKGROUND: It is unknown how the efficacy and safety of mineralocorticoid receptor antagonists vary according to duration of heart failure with reduced ejection fraction (HFrEF). OBJECTIVES: In this study, we sought to evaluate the safety and efficacy of eplerenone according to duration of HFrEF. METHODS: In the EMPHASIS-HF trial, 3 patient groups were created according to HFrEF duration: <1 year, 1 to <5 years, and ≥5 years. The primary outcome was the composite of heart failure (HF) hospitalization or cardiovascular death. Outcomes were adjusted for prespecified prognostic variables and examined with the use of Cox regression models. RESULTS: The numbers of patients in each group were: 975, <1 year; 769, 1 to <5 years; and 988, ≥5 years. Patients with longer-standing HF were older and more frequently had cardiovascular and noncardiovascular comorbidities. The rate of the primary outcome (per 100 person-years) increased with HFrEF duration: 9.8 (95% CI: 8.4-11.4) for <1 year, 13.5 (95% CI: 11.6-15.7) for 1 to <5 years, and 17.6 (95% CI: 15.6-19.8) for ≥5 years. The benefits of eplerenone were consistent across HF duration: HRs for the primary outcome were 0.57 (95% CI: 0.42-0.79) for <1 year, 0.81 (95% CI: 0.60-1.10) for 1 to <5 years, and 0.61 (95% CI: 0.48-0.78) for ≥5 years; Pinteraction = 0.24. The absolute benefit was greatest in the longest-duration group: the number needed to treat for the primary outcome was 14 for <1 year, 13 for 1 to <5 years, and 10 for ≥5 years duration. CONCLUSIONS: Patients with longer-standing HFrEF had worse clinical status and a higher rate of events, but the benefit of eplerenone was consistent regardless of HFrEF duration. (A Comparison of Outcomes in Patients in NYHA Class II Heart Failure When Treated With Eplerenone or Placebo in Addition to Standard Heart Failure Medicines [EMPHASIS-HF]; NCT00232180).

Long-term effect of eplerenone treatment in children with chronic allograft nephropathy.

BACKGROUND: Literature supports the protective role of mineralocorticoid antagonist (MRA) against the renal injury induced by aldosterone in kidney transplant recipients. However, there is limited data available regarding the safety and efficacy of MRAs in pediatric renal transplant patients. Therefore, we aimed to investigate the effect of long-term eplerenone administration in children with chronic allograft nephropathy (CAN). METHODS: Twenty-six renal transplant children with biopsy-proven CAN, an estimated glomerular filtration rate (eGFR ) > 40 mL/min per 1.73 m2 and with a significant proteinuria were included. Selected patients were randomly divided into two groups as follows; Group 1 (n = 10) patients received 25 mg/day eplerenone and Group 2 (n = 16) patients did not receive eplerenone for 36 months. Patients were examined in the renal transplant outpatient clinic biweekly for the first month and once a month thereafter. The primary outcome of the patients was compared. RESULTS: Mean eGFR stayed stable in group 1 patients, but significantly decreased in group 2 at 36 months (57.53 ± 7.53 vs. 44.94 ± 8.04 mL/min per 1.73 m2 , p = .001). Similarly, spot protein-creatinine ratio was significantly lower in group 1 compared to group 2 patients at 36 months (1.02 ± 7.53 vs. 3.61 ± 0.53, p < .001). Eplerenone associated hyperkalemia was not observed in group 1 patients (4.6 ± 0.2 vs. 4.56 ± 0.3, p = .713). CONCLUSION: The long-term eplerenone administration blunted the chronic allograft nephropathy by maintaining a stable eGFR levels and decreasing urine protein-creatinine ratio. Eplerenone associated hyperkalemia was not observed in our study.

The Effectiveness of Eplerenone vs Spironolactone on Left Ventricular Systolic Function, Hospitalization and Cardiovascular Death in Patients With Chronic Heart Failure-HFrEF.

Background: 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. Objective: 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. Methods: 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. Results: 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). Conclusion: 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.

Time to clinical benefit of eplerenone among patients with heart failure and reduced ejection fraction: A subgroups analysis from the EMPHASIS-HF trial.

AIM: Eplerenone reduces the risk of cardiovascular death or first hospitalization for heart failure (HF) in patients with HF and a reduced ejection fraction (HFrEF), but it is still frequently underused in routine practice. We evaluated the time course of benefits of eplerenone after its initiation in HFrEF patients from the EMPHASIS-HF trial. METHODS AND RESULTS: The EMPHASIS-HF trial was a double-blind randomized clinical trial assessing the effect of eplerenone in patients (n = 2737, mean age 68.6 ± 7.6 years, 22.3% women) with HFrEF and mild symptoms. The time trajectories for the effect of eplerenone versus placebo on the primary composite endpoint (cardiovascular death or first hospitalization for HF) were investigated using Cox proportional hazards models with truncated data at each day post-randomization. A significant reduction in the primary composite endpoint was observed 26 days after randomization (hazard ratio 0.58; 95% confidence interval, 0.34-1.00, p = 0.049). Eplerenone was first associated with a significant reduction in the primary endpoint in 35 days or less in most subgroups, including patients with HF history ≥18 months (day 24), estimated glomerular filtration rate <60 ml/min (day 12), ischaemic HF aetiology (day 28), age ≥65 years (day 28), narrow QRS (day 30), higher MAGGIC score (day 35), lower potassium (day 30), left ventricular ejection fraction ≥30% (day 28) or already treated with beta-blockers (day 25). CONCLUSIONS: Eplerenone provides statistically significant and clinically meaningful benefits shortly after treatment initiation in most patients, irrespective of clinical profile. This result reinforces the need for an early initiation of eplerenone in HFrEF, as part of rapidly instituting guideline-directed medical therapy.

Role of eplerenone in the threatment of cardiovascular diseases.

Eplerenone is a selective mineralocorticoid receptor antagonist. Its approved for the therapy of patients with chronic heart failure with left ventricular systolic dysfunction and for the patients after myocardial infarction complicated by heart failure and left ventricular dysfunction. It´s also recommended for the therapy of primary hyperaldosteronism and the treatment of drug resistant hypertension.

Randomized controlled trials in central serous chorioretinopathy: A review.

Central serous chorioretinopathy (CSCR), a common chorioretinal disease, presents with a myriad of manifestations. Acute CSCR presents with localized neurosensory detachment whereas chronic CSCR may show widespread retinal pigment epithelium (RPE) changes, chronic shallow subretinal fluid, and choroidal neovascularization (CNV) suggestive of a variable natural history leading to suboptimal visual outcomes. Even though multiple treatment options including laser photocoagulation, photodynamic therapy, micropulse laser, anti-vascular endothelial growth factors, and systemic drugs (spironolactone, eplerenone, melatonin, mifepristone) are available, there is an absence of any standardized treatment protocol or gold standard treatment modality. Moreover, their performance compared to observation especially in acute CSCR is still debatable. Compared to other chorioretinal diseases such as age-related macular degeneration, diabetic retinopathy, diabetic macular oedema, and retinal vein occlusion, there is a relative dearth of randomized controlled trials in CSCR. Multiple inconsistencies including reliance on history of disease duration, variable inclusion criteria/disease descriptors/study endpoints, and availability of multiple treatment modalities lead to difficulties in designing RCTs. A consensus-based treatment protocol, therefore, is still elusive. We reviewed the literature and compiled the list of papers published to date, wherein we analyse and compare the inclusion criteria, imaging modalities, study endpoints, study duration, and study results. Correcting these discrepancies and deficiencies will help standardize future study designs, facilitating a next step toward a standardized treatment protocol.

Hyperkalemia by eplerenone or esaxerenone in the presence or absence of clarithromycin in hypertensive patients: a retrospective observational cohort study.

OBJECTIVE: Mineralocorticoid receptor antagonists (MRAs), eplerenone and esaxerenone, cause hyperkalemia dose-dependently. We investigated the cytochrome P450 3A4-mediated drug-drug interaction between the MRAs and clarithromycin. METHODS: This retrospective observational study included adult hypertensive patients with MRA plus clarithromycin or MRA alone with a propensity score matching (1:1). The difference in serum potassium level (ΔK, maximum level - baseline level) between groups was compared using the Mann-Whitney U -test. Linear regression analysis was used to detect variables that correlated with ΔK in patients with MRA plus clarithromycin. RESULTS: After propensity score matching (each nine patients), serum potassium level was elevated after treatment with MRA plus clarithromycin [4.3 (3.5 to 5.1) meq/l to 4.9 (4.0 to 5.5) meq/l, P  = 0.0234] and MRA alone [4.3 (4.0 to 4.7) meq/l to 4.6 (4.4 to 5.2) meq/l, P  = 0.0469]. Although there was no significant difference in ΔK between groups [MRA plus clarithromycin: 0.5 (0.1 to 1.1) meq/l vs. MRA alone: 0.3 (0.1 to 1.2) meq/l, P  = 0.7231], ΔK was significantly higher in esaxerenone plus clarithromycin than in esaxerenone alone [0.6 (0.5 to 1.1) meq/l vs. 0.1 (0.1 to 0.2) meq/l, P  = 0.0495]. Conversely, clarithromycin did not show a significant effect on ΔK in patients with eplerenone [0.4 (-0.2 to 1.2) meq/l vs. 0.8 (0.1 to 1.3) meq/l, P  = 0.5745]. A positive correlation was found between ΔK and age in patients with MRA plus clarithromycin ( y  = 0.03 ×  x - 1.38, r  = 0.71, P  = 0.0336). CONCLUSION: The drug-drug interaction between MRAs and clarithromycin was evident, particularly in esaxerenone. Serum potassium levels should be closely monitored in older patients.

Choroidal modifications assessed by means of choroidal vascularity index after oral eplerenone treatment in chronic central serous chorioretinopathy.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Primary aldosteronism in pregnancy.

Primary aldosteronism (PA) is the most common form of secondary hypertension. Although hypertensive disorders seem to affect around 5-10% of pregnancies worldwide, literature counts less than 80 cases of PA diagnosed during the peri-partum period. In this review we discuss about current knowledge on pathophysiology, natural history, diagnosis and treatment of PA in pregnancy. Because of the physiologic changes in the renin-angiotensin-aldosterone system (RAAS) and the contraindication to both confirmatory test and subtype differentiation, diagnosis of PA during pregnancy is challenging and relies mostly on detection of low/suppressed renin and high aldosterone levels. The course of pregnancy in patients with PA is highly variable, ranging from progesterone-induced amelioration of blood pressure (BP) control to severe and resistant hypertension with potential maternal and fetal complications. Mineralcorticoid receptor antagonists (MRA) are the recommended and most effective drugs for treatment of PA. As the anti-androgenic effect of spironolactone can potentially interfere with sexual development, their prescription is not recommended during pregnancy. On the other side, eplerenone, has proven to be safe and effective in 6 pregnant women and may be added to conventional first line drug regimen in presence of resistant hypertension or persistent hypokalemia. Ideally, patients with unilateral forms of PA should undergo adrenalectomy prior to conception, however, when PA is diagnosed during pregnancy and medical therapy fails to adequately control hypertension or its complications, adrenalectomy can be considered during the second trimester in case of unilateral adrenal mass at MRI-scan.

Evaluating the clinical and mechanistic effects of eplerenone and amiloride monotherapy, and combination therapy with cinacalcet, in primary hyperparathyroidism: A placebo-controlled randomized trial.

OBJECTIVES: Human physiology and epidemiology studies have demonstrated complex interactions between the renin-angiotensin-aldosterone system, parathyroid hormone and calcium homeostasis. Several of these studies have suggested that aldosterone inhibition may lower parathyroid hormone (PTH) levels. The objective of this study was to assess the effect of 4 weeks of maximally tolerated mineralocorticoid receptor antagonist therapy with eplerenone on PTH levels in patients with primary hyperparathyroidism (P-HPT) when compared to amiloride and placebo. We also investigated the synergistic effect of these interventions when combined with cinacalcet for an additional 2 weeks. DESIGN: Randomized, double-blinded, three parallel-group, placebo-controlled trial. PATIENTS: Patients with P-HPT. RESULTS: Most patients were women (83%) and White (76%). Maximally tolerated doses of eplerenone and amiloride induced significant reductions in blood pressure and increases in renin and aldosterone production; however, despite these physiologic changes, neither intervention induced significant changes in PTH or calcium levels when compared to the placebo. Both eplerenone and amiloride therapy induced significant reductions in procollagen type 1 N-terminal propeptide levels when compared to placebo. When cinacalcet therapy was added, PTH and calcium levels were markedly reduced in all groups; however, there was no significant difference in PTH or serum calcium reductions between groups. CONCLUSIONS: Although maximally tolerated therapy with eplerenone and amiloride induced expected changes in renin, aldosterone and blood pressure, there were no meaningful changes in PTH or serum calcium levels in P-HPT patients. These results suggest that inhibition of aldosterone action does not have a clinically meaningful role in medical therapy for P-HPT.

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.

PURPOSE: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Effect of eplerenone on clinical stability of Japanese patients with acute heart failure.

BACKGROUND: In the EARLIER (Efficacy and Safety of Early Initiation of Eplerenone Treatment in Patients with Acute Heart Failure) trial, eplerenone did not reduce heart failure (HF) hospitalizations or all-cause mortality in 300 patients admitted for acute HF (AHF). However, the trial might have been underpowered for these endpoints, and a comprehensive overview of the effect of eplerenone on diuretic doses and patients' clinical stability is warranted. METHODS: The EARLIER trial included Japanese patients hospitalized for AHF randomly assigned to eplerenone or placebo over 6 months. Cox proportional hazards and mixed-effects models were used for analyses. RESULTS: Three hundred patients were included (mean age, 67 ± 13 years; 73% males). The median furosemide equivalent dose was 40 (20-62) mg at randomization. Patients with higher furosemide-equivalent doses had more severe signs and symptoms of congestion and a higher risk of all-cause mortality or HF hospitalization during 6-month follow-up (adjusted-hazard ratio per 10 mg/day increase = 1.25, 95% confidence interval: 1.05-1.49). Eplerenone significantly decreased furosemide-equivalent diuretic doses and b-type natriuretic levels throughout the follow-up (overall-joint-p < 0.05 for both) and reduced E/e' and inferior vena cava diameter at 4 weeks (both p < 0.05). Additionally, eplerenone significantly reduced left ventricular (LV) end-diastolic diameter at 24 weeks (p < 0.05). CONCLUSIONS: Eplerenone treatment improved the clinical stability particularly during short period following hospitalization for AHF, translated by lower diuretic doses, natriuretic peptide levels, indirect markers of filling pressure and venous congestion, and a smaller LV volume.

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

PURPOSE: 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. METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.

Effects of plasma aldosterone concentration and treatment with eplerenone on the survival of cats with chronic kidney disease.

This study investigated the plasma aldosterone concentration (PAC) in cats with chronic kidney disease (CKD) and retrospectively evaluated the survival of cats with high PAC. Furthermore, this study prospectively examined eplerenone's effect on survival time in CKD cats with high PAC. The PAC was measured retrospectively in blood samples obtained from 156 client-owned cats that visited a veterinary hospital. The cats were designated into 2 groups: clinically healthy (n = 101) and those with CKD (n = 55). The PAC was measured by solid-phase radioimmunoassay; median (minimum-maximum) PAC in healthy cats was 97 pg/mL (range: 10 to 416 pg/mL) and the upper limit (95th percentile) was 243 pg/mL. In the CKD group, PAC [126 pg/mL (range: 10 to 981 pg/mL)] was higher (P < 0.01) than in the clinically healthy group. In cats with CKD, the survival time of those with high PAC (n = 16) (> 243 pg/mL) was shorter (P = 0.019) than that of those (n = 39) with normal PAC. Administering an aldosterone antagonist, eplerenone, at 2.5 to 5 mg/kg body weight prolonged survival (P = 0.005) in CKD cats with high PAC (n = 8). In conclusion, PAC could be a prognostic marker of CKD in cats and eplerenone may prolong survival in cats with CKD and a high PAC.

Effets de la concentration plasmatique d'aldostérone et du traitement à l'éplérénone sur la survie des chats atteints d'insuffisance rénale chronique. Cette étude a examiné la concentration plasmatique d'aldostérone (PAC) chez les chats atteints d'insuffisance rénale chronique (IRC) et a évalué rétrospectivement la survie des chats ayant une PAC élevée. De plus, cette étude a examiné de manière prospective l'effet de l'éplérénone sur le temps de survie chez les chats IRC avec une PAC élevée. La PAC a été mesurée rétrospectivement dans des échantillons de sang prélevés sur 156 chats appartenant à des clients ayant visité un hôpital vétérinaire. Les chats ont été répartis en 2 groupes : cliniquement sains (n = 101) et ceux atteints d'IRC (n = 55). La PAC a été mesurée par radio-immunodosage en phase solide; la PAC médiane (minimale-maximale) chez les chats sains était de 97 pg/mL (plage : 10 à 416 pg/mL) et la limite supérieure (95e centile) était de 243 pg/mL. Dans le groupe IRC, la PAC [126 pg/mL (plage : 10 à 981 pg/mL)] était plus élevée (P < 0,01) que dans le groupe cliniquement sain. Chez les chats atteints d'IRC, le temps de survie de ceux avec une PAC élevée (n = 16) (> 243 pg/mL) était plus court (P = 0,019) que celui de ceux (n = 39) avec une PAC normale. L'administration d'un antagoniste de l'aldostérone, l'éplérénone, à raison de 2,5 à 5 mg/kg de poids corporel a prolongé la survie (P = 0,005) chez les chats atteints d'IRC avec une PAC élevée (n = 8). En conclusion, la PAC pourrait être un marqueur pronostique de l'IRC chez le chat et l'éplérénone pourrait prolonger la survie des chats atteints d'IRC et d'une PAC élevée.(Traduit par Dr Serge Messier).