Search

Objective: Repurposing Eplerenone (EPL) for wound healing through in silico molecular docking to explore its therapeutic potential beyond its traditional use (antihypertensive drug). In this study, for a first time we investigated the potential of EPL- loaded pectin nanoparticles to enhance human skin proliferation. Methods: Ionotropic gelation method was used for preparing these EPL-loaded PN using calcium chloride as a cross-linker. Design® Expert software was used to utilize a full factorial 23 design, where the selected factors were the pectin concentration (X1), EPL amount (X2), and pectin: calcium chloride concentration (X3). The selected responses were the EPL entrapment efficiency percentage, particle size and zeta potential for determining the optimum formula for further studies such as in-vitro release studies, transmission electron microscopy (TEM), X-ray diffraction, cell culture study and in-vitro evaluation on human skin fibroblast proliferation cell. Results: The selected system demonstrated high entrapment efficiency (80.56 ± 0.62%), a particle size of 509.1 ± 45.5 nm, and good zeta potential value (-21.73 ± 2.1 mV). A spherical morphology with no aggregation using TEM and amorphization of the crystalline drug in X-ray diffraction were obtained. The Sulfo-Rhodamine B assay was applied for its effect on cell viability on human skin cells, and the selected concentration was 50 μg/mL. Conclusions: The wound healing assay on human skin fibroblasts using scratch wound technique showed the superiority of EPL on wound healing; suggesting its promising effect in enhancing skin healing and tissue regeneration. Moreover, pectin activity as a wound healing accelerator, promoting a synergistic effect. [ABSTRACT FROM AUTHOR]

Introduction: Finerenone, a third-generation non-steroidal mineralocorticoid receptor antagonist (MRA), offers a targeted approach to managing cardiovascular outcomes, particularly in patients with chronic kidney disease (CKD) and type 2 diabetes (T2D). Unlike traditional MRAs such as spironolactone and eplerenone, which can cause off-target hormonal side effects and hyperkalemia, Finerenone selectively binds to mineralocorticoid receptors, reducing these risks. Recent randomized controlled trials have demonstrated Finerenone's potential to improve cardiovascular outcomes, making it a promising alternative in the management of heart failure and other cardiovascular conditions associated with CKD and T2D. Methods: We conducted a scoping review using PRISMA guidelines. A search for "Finerenone" in the PubMed, Embase, and Cochrane Library databases included randomized controlled trials (RCTs), post hoc analyses, and relevant meta-analyses on cardiovascular outcomes. Data were synthesized narratively, assessing study quality through strengths and limitations. Discussion: Finerenone has shown significant benefits and a superior safety profile compared with traditional MRAs like spironolactone and eplerenone in managing CKD, T2D, and heart failure. It effectively reduces cardiovascular and renal events while minimizing risks such as hyperkalemia and hormonal side effects associated with steroidal MRAs. Future studies, including the REDEFINE-HF, FINALITY-HF, and CONFIRMATION-HF trials, will further explore Finerenone's potential across diverse heart failure phenotypes, including its role in heart failure with mildly reduced and preserved ejection fractions, potentially establishing it as a cornerstone therapy in heart failure management. Conclusions: Finerenone represents a significant advancement in MRA therapy, offering enhanced safety and efficacy in managing cardiovascular outcomes in CKD and T2D patients. The current evidence supports its use as a promising alternative to traditional MRAs, particularly in patients intolerant to steroidal MRAs. Further trials are needed to fully establish its potential across diverse patient populations, including those with varying heart failure phenotypes. [ABSTRACT FROM AUTHOR]

Purpose To evaluate the efficacy of eplerenone in central serous chorioretinopathy (CSCR) patients in a clinical trial design. Methods In this double-blind clinical trial, naive acute. CSCR patients were divided into two groups: treatment with eplerenone 25 mg daily in the 1st week followed by 50 mg for the next 3 weeks and placebo group. Best-corrected visual acuity (BCVA), central macular thickness (CMT), macular volume (MV), and choroidal thickness (CT) were measured before and after 1 month of the intervention using the optical coherence tomography technique. Results Thirty-one CSCR (male: 23, female: 8) and 25 CSCR patients (male: 18, female: 7) with the mean age of 35.65 ± 5.94 and 37.08 ± 6.41 years were recruited and divided randomly into treatment and placebo groups, respectively. BCVA improved significantly in the treatment group (from 0.28 ± 0.26 to 0.11 ± 0.14, P = 0.002) compared with the placebo group (from 0.31 ± 0.26 to 0.21 ± 0.14, P = 0.052). Although CT, CMT, and MV improved significantly in each group, there were no significant differences between the groups. Conclusion In this study, we found favorable short-term clinical effects of eplerenone in acute CSCR patients, showing the pivotal role of mineralocorticoid receptors in the retina.

PURPOSE: To report eplerenone use by retina specialists worldwide for central serous chorioretinopathy (CSCR). METHODS: A self-reporting questionnaire was distributed to retina specialists worldwide to gather clinicians perspectives on CSCR cases treated, eplerenone dosage and duration, reasons to use it, and side effects. RESULTS: The survey included 241 retina specialists (122 Indian and 119 international) with an average experience of 15.69 ± 9.59 years. Oral eplerenone was used to treat CSCR by 149 (62%) participants. Only 6% (n = 9) had easy access to verteporfin dye and photodynamic therapy. 30 (20%) of the 149 respondents changed their treatment with eplerenone after VICI trial results. Eplerenone was prescribed mostly for chronic CSCR (n = 86, 58%), regardless of involvement laterality. 62% (n = 92) had fewer than 25% CSCR cases treated with eplerenone. 85 (57%) respondents used eplerenone only when other treatments failed, while 36 (24%) used it as first-line treatment. 73 (49%) respondents, prescribed eplerenone at a 50 mg daily dose and 137 (92%) retina specialists used eplerenone for 0-3 months. The drugs efficacy dissatisfied 21 (14%) study participants. 124 (83%) study participants did not encounter any ocular or systemic side effects with eplerenone use. Eplerenone related kidney and electrolyte issues were noted by 11 (7%) study participants. CONCLUSION: The treatment of CSCR varies around the world and is primarily influenced by the photodynamic therapy availability and the findings of VICI trial. Despite the limited benefit of eplerenone reported by the VICI trial, it is still used as evidenced by real-world experience. TRIAL REGISTRATION NUMBER: Not applicable.

Abstract Background Eplerenone and spironolactone, recognized as mineralocorticoid receptor antagonists (MRAs), have been reported to improve clinical prognosis among individuals diagnosed with heart failure (HF). However, the difference in the clinical effects between eplerenone and spironolactone in individuals with HF remains uncertain. We aimed to assess the impact of eplerenone compared to spironolactone on clinical outcomes within the HF population. Methods An extensive search was executed in several databases (PubMed, Web of Science, Scopus, Cochrane Library). All relevant studies evaluating eplerenone compared to spironolactone in patients with HF were included. Dichotomous data were pooled as Hazard ratio (HR) or Risk ratio (RR) with a 95% confidence interval (CI). Our main outcome was all-cause mortality. Secondary outcomes included death from cardiovascular causes, treatment withdrawal, and gynecomastia. Results Ten studies, comprising 21,930 HF individuals, were included in our investigation. Eplerenone showed a lower risk of all-cause mortality (HR = 0.78, 95%CI [0.64 to 0.94], P = 0.009) and cardiovascular mortality (HR = 0.54, 95%CI [0.39, 0.74], P = 0.0001) compared to spironolactone. Furthermore, eplerenone exhibited a reduced risk of treatment withdrawal (RR = 0.69, 95% CI [0.62, 0.78], P = 0.0001) and gynecomastia (RR = 0.07, 95% CI [0.02 to 0.31], P = 0.0001) than spironolactone. Conclusion Eplerenone revealed lower all-cause and cardiovascular mortality events in comparison to spironolactone. Moreover, eplerenone was associated with lower gynecomastia and treatment withdrawal events compared to spironolactone. Further well-designed randomized controlled trials are still warranted better to identify the clinical differences between eplerenone and spironolactone. Trial registration Protocol registration: https://doi.org/10.17605/OSF.IO/VNMGK

Mineralocorticoid receptor antagonists (MRAs) have proven to be highly effective therapeutic options in the treatment of patients with heart failure with reduced ejection fraction (HFrEF) based on randomized clinical trials. Current evidence in these patients clearly indicates that MRAs reduce morbidity and mortality in heart failure patients. Results from the three major trials involving HFrEF patients (RALES, EPHESUS, EMPHASIS-HF) have led both spironolactone and eplerenone to become pivotal drugs in the management of HFrEF patients, with class I indications according to ESC and ACC/AHA heart failure guidelines. The anti-remodeling and anti-fibrotic effects of MRAs may extend their clinical utility to a broader cardiovascular patient population, such as asymptomatic HFrEF patients and certain populations of HFpEF patients. Regarding the latter, the TOPCAT trial demonstrated that although the primary endpoint of the trial was negative, spironolactone significantly reduced heart failure-related hospitalizations without a detrimental effect on mortality. Hopefully, results from future prospective studies, which include investigations with the latest third-generation MRAs (finerenone), will expand the clinical indications of this drug class.

Aims Methods Conclusion Benefits of mineralocorticoid receptor antagonists (MRAs) in heart failure with preserved and mildly reduced ejection fraction (HFpEF/HFmrEF) have not been established. Conventional randomized controlled trials are complex and expensive. The Spironolactone Initiation Registry Randomized Interventional Trial in Heart Failure with Preserved Ejection Fraction (SPIRRIT‐HFpEF) is a unique pragmatic registry‐based randomized controlled trial.SPIRRIT‐HFpEF is a multicentre, prospective, randomized, open‐label, blinded endpoint trial conducted on platforms in the Swedish Heart Failure Registry (SwedeHF) and the United States (US) Trial Innovation Network. Patients with HFpEF/HFmrEF are randomized 1:1 to spironolactone (or eplerenone) in addition to usual care, versus usual care alone. The primary outcome is total number of cardiovascular deaths and hospitalizations for heart failure. Outcomes are collected from Swedish administrative complete coverage registries and a US call centre and subsequently adjudicated. Simple eligibility criteria were based on data available in SwedeHF: heart failure as outpatient or at discharge from hospital, left ventricular ejection fraction ≥40%, N‐terminal pro‐B‐type natriuretic peptide >300 ng/L (in sinus rhythm) or >750 ng/L (in atrial fibrillation), with pre‐specified adjustment for elevated body mass index, and chronic loop diuretic use. Power and sample size assessments were based on an event‐driven design allowing enrolment over approximately 6 years, and application of hazard ratios from the TOPCAT trial, Americas subset. The final sample size is expected to be approximately 2400 patients.SPIRRIT‐HFpEF will be informative on the effectiveness of generic MRAs in HFpEF and HFmrEF, and on the feasibility of conducting pragmatic and registry‐based trials in heart failure and other chronic conditions. [ABSTRACT FROM AUTHOR]

Background: Eplerenone and spironolactone, recognized as mineralocorticoid receptor antagonists (MRAs), have been reported to improve clinical prognosis among individuals diagnosed with heart failure (HF). However, the difference in the clinical effects between eplerenone and spironolactone in individuals with HF remains uncertain. We aimed to assess the impact of eplerenone compared to spironolactone on clinical outcomes within the HF population. Methods: An extensive search was executed in several databases (PubMed, Web of Science, Scopus, Cochrane Library). All relevant studies evaluating eplerenone compared to spironolactone in patients with HF were included. Dichotomous data were pooled as Hazard ratio (HR) or Risk ratio (RR) with a 95% confidence interval (CI). Our main outcome was all-cause mortality. Secondary outcomes included death from cardiovascular causes, treatment withdrawal, and gynecomastia. Results: Ten studies, comprising 21,930 HF individuals, were included in our investigation. Eplerenone showed a lower risk of all-cause mortality (HR = 0.78, 95%CI [0.64 to 0.94], P = 0.009) and cardiovascular mortality (HR = 0.54, 95%CI [0.39, 0.74], P = 0.0001) compared to spironolactone. Furthermore, eplerenone exhibited a reduced risk of treatment withdrawal (RR = 0.69, 95% CI [0.62, 0.78], P = 0.0001) and gynecomastia (RR = 0.07, 95% CI [0.02 to 0.31], P = 0.0001) than spironolactone. Conclusion: Eplerenone revealed lower all-cause and cardiovascular mortality events in comparison to spironolactone. Moreover, eplerenone was associated with lower gynecomastia and treatment withdrawal events compared to spironolactone. Further well-designed randomized controlled trials are still warranted better to identify the clinical differences between eplerenone and spironolactone. Trial registration: Protocol registration: https://doi.org/10.17605/OSF.IO/VNMGK [ABSTRACT FROM AUTHOR]

Eplerenone is a medication used to manage hypertension and chronic heart failure by inhibiting aldosterone receptors. This study's objective is to prepare sublingual dissolving films containing Eplerenone, to enhance patient adherence, avoid first-pass metabolism, and minimize the need for repeated dosing. To achieve this goal, eight different formulations were prepared using a solvent-casting method. The study examined how various formulation factors influenced the physical and mechanical characteristics of the films, as well as their drug-release behavior. Notably, the results showed that the Eplerenone oral film, which included a combination of hydroxypropyl methylcellulose (HPMC E5) and polyvinyl alcohol (PVA), exhibited the fastest disintegration time, dissolving within just 27 seconds. Furthermore, formula F3, containing 25 mg of HPMC E5, 25 mg of PVA, and 30% glycerin, demonstrated a remarkable drug release rate of 72.4% within a 2-minute period with satisfactory mechanical properties. To summarize, this investigation successfully developed sublingual dissolving films for Eplerenone to improve patient adherence and decrease the necessity for frequent dosing. These films disintegrate rapidly and provide effective drug release, offering a patient-friendly alternative for managing conditions such as hypertension and chronic heart failure. [ABSTRACT FROM AUTHOR]

Mineralocorticoid receptor antagonists (MRAs) are one of the renin–angiotensin–aldosterone system inhibitors widely used in clinical practice. While spironolactone and eplerenone have a long-standing profile in clinical medicine, finerenone is a novel agent within the MRA class. It has a higher specificity for mineralocorticoid receptors, eliciting less pronounced adverse effects. Although approved for clinical use in patients with chronic kidney disease and heart failure, intensive non-clinical research aims to further elucidate its mechanism of action, including dose-related selectivity. Within the field, animal models remain the gold standard for non-clinical testing of drug pharmacological and toxicological properties. Their role, however, has been challenged by recent advances in in vitro models, mainly through sophisticated analytical tools and developments in data analysis. Currently, in vitro models are gaining momentum as possible platforms for advanced pharmacological and pathophysiological studies. This article focuses on past, current, and possibly future in vitro cell models research with clinically relevant MRAs. [ABSTRACT FROM AUTHOR]

Introduction: Eplerenone is approved for the treatment of hypertension as well as symptomatic heart failure with reduced ejection fraction (HFrEF) following an acute myocardial infarction. However, the adverse events (AEs) have not been systematically analyzed. The aim of this study was to identify adverse drug reactions (ADRs) related to eplerenone using the FDA Adverse Event Reporting System (FAERS) database. By identifying previously unreported AEs, the study could potentially contribute to updating the drug's label. Methods: In order to find significant AEs, four algorithms, including Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN) and Empirical Bayesian Geometric Mean (EBGM), were used to analyze the signal strength of the ADRs connected to eplerenone that were gathered from the FAERS database over the previous 20 years. Results: From 2004Q1 to 2023Q4, a total of 20, 629, 811 reported cases were gathered from the FAERS database for this study. After processing the data and filtering, 1,874 case reports were analyzed. Of these cases, 1,070 AEs were identified, 128 of which were eplerenone-related ADRs. We investigated the occurrence of ADRs induced by eplerenone in 27 organ systems. Our study showed that the AEs listed in the medication's package insert correspond with those listed in the literature, including hyperkalemia and increased creatinine. Additionally, the prescription label for eplerenone does not include all system organ class (SOC) terms, like Vascular disorders, hepatobiliary Disorders, etc. Discussion: The study used multiple algorithms to quantify the signal strength and then identified any previously unrecognized ADRs, further studies are needed to confirm the association of ADRs with eplerenone. The findings of this study may provide important insights into the safety profile of eplerenone, ensure that healthcare providers have up-to-date information about their potential risks and help guide them in the correct use of the drug. [ABSTRACT FROM AUTHOR]

Objectives: Evidence suggests that renal function increasingly deteriorates in patients with apparently treatment-resistant hypertension (ATRH) in comparison with those who have non-resistant arterial hypertension (NAH). We aimed to assess the long-term decline in renal function between these patient groups and identify specific risk factors contributing to the progression of renal dysfunction. Methods: Data for 265 patients with ATRH and NAH in a hypertension excellence centre were retrospectively evaluated. Demographic characteristics, co-morbidities, laboratory findings, secondary causes of hypertension, medication and exposure to contrast agents were assessed. To address differences between groups, adjustment with linear mixed-effect models was used. Results: Data from the first 4 years of follow-up were evaluated. After adjustment for age and diabetes, which were identified as independent risk factors for renal dysfunction progression in the study cohort, the mean decrease in estimated glomerular filtration rate per year was steeper with ATRH than with NAH (−1.49 vs. −0.65 mL/min/1.73 m2 per year; difference in slope, 0.83 mL/min/1.73 m2 per year; 95% confidence interval [CI]: 0.25–1.41, p = 0.005). In subgroup analyses, without Holm–Bonferroni correction, the prescription of MRA indicated a faster decline in renal function in ATRH. Following correction, no specific therapeutic risk factor was associated with faster progression of renal dysfunction. Conclusions: Renal function declines twice as fast with ATRH compared with NAH, independently of age and diabetes. Larger studies are needed to reveal risk factors for renal dysfunction in patients with hypertension.

Kidney dysfunction often leads to reluctance to start or continue life-saving heart failure (HF) therapy. This study sought to examine the efficacy and safety of mineralocorticoid receptor antagonists (MRAs) in patients with HF with reduced ejection fraction experiencing significant kidney dysfunction. We pooled individual patient data from the RALES (Randomized Aldactone Evaluation Study) and EMPHASIS-HF (Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure) trials. The association between MRA treatment and outcomes was assessed according to whether the estimated glomerular filtration rate (eGFR) declined to <30 mL/min/1.73 m2 or not. The primary outcome was cardiovascular death or HF hospitalization. Among 4,355 patients included, 295 (6.8%) experienced a deterioration of eGFR after randomization to <30 mL/min/1.73 m2. These patients had more impaired baseline cardiac and kidney function (eGFR 47.3 ± 13.4 mL/min/1.73 m2 vs 70.5 ± 21.8 mL/min/1.73 m2) and had a higher risk of the primary outcome than patients without eGFR deterioration (HR: 2.49; 95% CI: 2.01-3.08; P < 0.001). However, the risk reduction in the primary outcome with MRA therapy was similar in those who experienced a decrease in eGFR to <30 mL/min/1.73 m2 (HR: 0.65; 95% CI: 0.43-0.99) compared with those who did not (HR: 0.63; 95% CI: 0.56-0.71) (P interaction = 0.87). In patients with a decrease in eGFR to <30 mL/min/1.73 m2, 21 fewer individuals (per 100 person-years) experienced the primary outcome with MRA treatment, vs placebo, compared with an excess of 3 more patients with severe hyperkalemia (>6.0 mmol/L). Because patients experiencing a decrease in eGFR to <30 mL/min/1.73 m2 are at very high risk, the absolute risk reduction with an MRA in these patients is large and this decline in eGFR should not automatically lead to treatment discontinuation. [Display omitted] [ABSTRACT FROM AUTHOR]

Stress is often associated with anxiety and depressive symptoms in adolescents. Stress is associated with components of metabolic syndrome and inflammation. The present study hypothesizes that aldosterone, more than corticosterone, promotes chronic stress-hepatic steatosis and fibrosis, as well as renal inflammation and fibrosis in young adult rats. Thirty-two young adult male Wistar rats of 51 days old were divided into four groups (n = 8 per group): Control (C), chronic unpredictable mild stress (CUMS), control plus vehicle (C plus veh), CUMS plus eplerenone, a selective aldosterone blocker (CUMS plus EP). On postnatal day 51, eplerenone was administered orally through a gastric tube two hours before the start of the stress test. The CUMS paradigm was administered once daily at different times, with no repetition of the stressor sequence for four weeks. Renal inflammation and fibrosis were measured, as well as liver glycogen, triacylglycerol, and fibrosis levels. The serum concentrations of corticosterone, aldosterone, sodium, and creatinine were measured in urine and serum. The CUMS group showed a high level of serum aldosterone without affecting the level of corticosterone, increased urinary sodium, tubular atrophy, glomerular sclerosis, the presence of inflammation, and fibrosis, without affecting creatinine, increased glycogen content, triacylglycerol, and moderate fibrosis in the liver, and treatment with eplerenone prevented the inflammation, fibrosis, glycogen, and triacylglycerol. Our results show that chronic stress-induced aldosterone promotes hepatic steatosis and renal injury more than corticosterone. The prevention by eplerenone supports our hypothesis. [ABSTRACT FROM AUTHOR]

Background: The renin-angiotensin-aldosterone system (RAAS) members, especially Ang II and aldosterone, play key roles in the pathogenesis of diabetic cardiomyopathy (DCM). Angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers combined with aldosterone receptor antagonists (mineralocorticoid receptor antagonists) have substantially improved clinical outcomes in patients with DCM. However, the use of the combination has been limited due to its high risk of inducing hyperkalemia. Methods: Type 1 diabetes was induced in 8-week-old male C57BL/6J mice by intraperitoneal injection of streptozotocin at a dose of 55 mg/kg for 5 consecutive days. Adeno-associated virus 9-mediated short-hairpin RNA (shRNA) was used to knock down the expression of ADAM17 in mice hearts. Eplerenone was administered via gavage at 200 mg/kg daily for 4 weeks. Primary cardiac fibroblasts were exposed to high glucose (HG) in vitro for 24 h to examine the cardiac fibroblasts to myofibroblasts transformation (CMT). Results: Cardiac collagen deposition and CMT increased in diabetic mice, leading to cardiac fibrosis and dysfunction. In addition, ADAM17 expression and activity increased in the hearts of diabetic mice. ADAM17 inhibition and eplerenone treatment both improved diabetes-induced cardiac fibrosis, cardiac hypertrophy and cardiac dysfunction, ADAM17 deficiency combined with eplerenone further reduced the effects of cardiac fibrosis, cardiac hypertrophy and cardiac dysfunction compared with single therapy in vivo. High-glucose stimulation promotes CMT in vitro and leads to increased ADAM17 expression and activity. ADAM17 knockdown and eplerenone pretreatment can reduce the CMT of fibroblasts that is induced by high glucose levels by inhibiting TGFβ1/Smad3 activation; the combination of the two can further reduce CMT compared with single therapy in vitro. Conclusion: Our findings indicated that ADAM17 knockout could improve diabetes-induced cardiac dysfunction and remodeling through the inhibition of RAAS overactivation when combined with eplerenone treatment, which reduced TGF-β1/Smad3 pathway activation-mediated CMT. The combined intervention of ADAM17 deficiency and eplerenone therapy provided additional cardiac protection compared with a single therapy alone without disturbing potassium level. Therefore, the combination of ADAM17 inhibition and eplerenone is a potential therapeutic strategy for human DCM. [ABSTRACT FROM AUTHOR]

Eplerenone (EPL) and spironolactone (SPR) belong to the class of potassium-sparing diuretics. Both drugs are prescribed for the treatment of hypertension and heart failure. Spironolactone is structurally like progesterone and binds to progesterone, androgen and mineralocorticoid receptors. Eplerenone is a selective mineralocorticoid receptor antagonist, so it lacks the anti-androgenic side effects of spironolactone. Using a thorough computer assisted literature survey; this review article touches upon the reported analytical methods for the quantification of both drugs in raw materials, pharmaceutical dosage forms and biological fluids. Bioanalytical methods are widely used for quantitative estimation of drugs and their metabolites in biological matrices. Various analytical methods such as spectrophotometry, spectrofluorimetry, HPLC, TLC, and UPLC have been used in laboratories for the quantitative analysis of these drugs in biological samples and pharmaceutical preparations. Therefore, the aim of this review is to give a summary of the current analytical methods used for the assay of both drugs. The review represents a guide for the QC labs and the bioequivalence centers to analyze the studied drugs. [ABSTRACT FROM AUTHOR]

Multiple studies have shown that finerenone (BAY 94-8862), a third-generation non-steroidal mineralocorticoid receptor antagonist (MRA), possesses different or superior mechanisms of action to traditional MRAs. Specifically, animal and cell-based experiments have demonstrated that this compound exerts multiple effects including fibrosis inhibition, reduced pulmonary artery pressure, improved diabetic retinopathy, enhanced endothelial functions, metabolic optimization as well as reduced oxidative stress, thereby exerting overall positive effects on renal and cardiovascular diseases. Consequently, clinical research, such as the FIGARO-DKD and FIDELIO-DKD trials, has demonstrated dual benefits for patients with type 2 diabetes mellitus and chronic kidney disease (T2DM-CKD), especially by validating MRAs’ potential in reducing risks of renal and cardiovascular composite endpoints. Currently, cardiovascular indications for finerenone are limited to patients with T2DM-CKD, while its use in non-T2DM CKD patients remains at clinical trial stages. Despite showing good safety and efficacy in T2DM-CKD patients, there are insufficient corresponding data for those presenting chronic kidney disease without diabetes (ndCKD). Furthermore, the application of this compound in diseases such as primary aldosteronism and its association with cancer risk need to be further validated through larger-scale and longer-term clinical studies. Nevertheless, the development of finerenone provides an additional option for treating cardiovascular and renal diseases. With further research, it is expected that finerenone will be relevant to a broader range of CKD patient populations by addressing current knowledge gaps to comprehensively evaluate its clinical value and potentially alter existing treatment strategies. The current review aims to comprehensively analyze the basic research and clinical advancements involving finerenone in order to explore its prospects for treating cardiovascular and renal diseases, while addressing unmet needs in current treatment strategies. Additionally, through a comprehensive analysis of relevant research findings, a deeper understanding of finerenone's drug characteristics will be provided alongside scientific guidance for future treatment strategies and their clinical significance.

Background and Aims Mineralocorticoid receptor antagonists (MRAs) improve cardiovascular outcomes in a variety of settings. This study aimed to assess whether cardioprotective effects of MRAs are modified by heart failure (HF) and atrial fibrillation (AF) status and to study their impact on AF events. Methods MEDLINE, Embase, and Cochrane Central databases were searched to 24 March 2023 for randomized controlled trials evaluating the efficacy of MRAs as compared with placebo or usual care in reducing cardiovascular outcomes and AF events in patients with or at risk for cardiovascular diseases. Random-effects models and interaction analyses were used to test for effect modification. Results Meta-analysis of seven trials (20 741 participants, mean age: 65.6 years, 32% women) showed that the efficacy of MRAs, as compared with placebo, in reducing a composite of cardiovascular death or HF hospitalization remains consistent across patients with HF [risk ratio = 0.81; 95% confidence interval (CI): 0.67–0.98] and without HF (risk ratio = 0.84; 95% CI: 0.75–0.93; interaction P =.77). Among patients with HF, MRAs reduced cardiovascular death or HF hospitalization in patients with AF (hazard ratio = 0.95; 95% CI: 0.54–1.66) to a similar extent as in those without AF (hazard ratio = 0.82; 95% CI: 0.63–1.07; interaction P =.65). Pooled data from 20 trials (21 791 participants, mean age: 65.2 years, 31.3% women) showed that MRAs reduce AF events (risk ratio = 0.76; 95% CI: 0.67–0.87) in both patients with and without prior AF. Conclusions Mineralocorticoid receptor antagonists are similarly effective in preventing cardiovascular events in patients with and without HF and most likely retain their efficacy regardless of AF status. Mineralocorticoid receptor antagonists may also be moderately effective in preventing incident or recurrent AF events. [ABSTRACT FROM AUTHOR]

Diabetic kidney disease (DKD) is a growing epidemic worldwide and a leading cause of end‐stage kidney disease. Mineralocorticoid receptor (MR) blockade using Finerenone is a recently approved therapeutic approach to slow down the progression of DKD in patients with type 2 diabetes in addition to other therapies such as angiotensin‐II converting enzyme inhibitors (ACEIs), angiotensin II receptor blockers (ARBs), sodium‐glucose co‐transporter 2 (SGLT2) inhibitors, and glucagon‐like peptide 1 (GLP‐1) analogs. This review elaborates on the pathophysiologic pathways activated by aldosterone (the human mineralocorticoid) in DKD, the pharmacology of three different generations of mineralocorticoid receptor antagonists (MRAs), specifically, spironolactone, eplerenone, and finerenone, and the mechanisms by which these MRAs elicit their protective effects on the kidney under diabetic settings. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

We aimed to assess the efficacy of eplerenone, a steroidal mineralocorticoid receptor antagonist known to reduce blood pressure and mitigate cardiovascular disease (CVD) progression, in retarding the progression of chronic kidney disease (CKD) and CVD in a rat model of type 4 cardiorenal syndrome (CRS). We grouped rats into four experimental categories: sham surgery, sham treatment with eplerenone, nephrectomy without eplerenone (Nx), and nephrectomy with eplerenone (Nx + EP). For the Nx + EP group, rats received five-sixths nephrectomy, inducing CKD and CVD conditions such as renal hypertension and hyperglycemia, and were then treated with eplerenone (100 mg/kg/day, orally) over 4 weeks after an initial 4-week observation period. Heart rate, blood pressure, blood sugar levels, and sympathetic nerve excitation were monitored biweekly. In addition, assessments of renal and cardiac tissues, including evaluation of renal tubulointerstitial injury, glomerular injury, and cardiomyocyte hypertrophy, were conducted at week 8. Eplerenone administration mitigated CKD and CVD progression in the Nx + EP group, evident by improved blood pressure (217.3 ± 5.4 versus 175.3 ± 5.6), blood sugar (121.8 ± 1.3 versus 145.6 ± 6.0) level, reduced sympathetic nerve excitation, and cardiomyocyte hypertrophy compared to the Nx group. However, renal tubulointerstitial injury, glomerular injury, and cardiovascular dysfunction, which were increased in rats with type 4 CRS, did not show significant changes with eplerenone treatment. Our study demonstrated that eplerenone treatment did not exacerbate type 4 CRS but improved blood pressure, blood sugar levels, sympathetic nerve excitation, and cardiomyocyte hypertrophy in this model. [ABSTRACT FROM AUTHOR]

The overactivation of the mineralocorticoid receptor (MR) promotes pathophysiological processes related to multiple physiological systems, including the heart, vasculature, adipose tissue and kidneys. The inhibition of the MR with classical MR antagonists (MRA) has successfully improved outcomes most evidently in heart failure. However, real and perceived risk of side effects and limited tolerability associated with classical MRA have represented barriers to implementing MRA in settings where they have been already proven efficacious (heart failure with reduced ejection fraction) and studying their potential role in settings where they might be beneficial but where risk of safety events is perceived to be higher (renal disease). Novel non-steroidal MRA have distinct properties that might translate into favourable clinical effects and better safety profiles as compared with MRA currently used in clinical practice. Randomised trials have shown benefits of non-steroidal MRA in a range of clinical contexts, including diabetic kidney disease, hypertension and heart failure. This review provides an overview of the literature on the systemic impact of MR overactivation across organ systems. Moreover, we summarise the evidence from preclinical studies and clinical trials that have set the stage for a potential new paradigm of MR antagonism. [ABSTRACT FROM AUTHOR]

Copyright of Canadian Journal of Hospital Pharmacy / Journal Canadien de la Pharmacie Hospitalière is the property of Canadian Society of Hospital Pharmacists and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)