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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]

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.

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]

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.

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Abstract 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 drug’s 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.

The latest anti-diabetic medication sodium-glucose co-transporter inhibitor along with the lowering of blood glucose has a cardioprotective and reno-protective effect, it has the ability to reduce the development of heart failure and decrease hospitalization in heart failure subjects with and without diabetes. This study was conducted to evaluate the effect of sodium-glucose co-transporter inhibitor dapagliflozin alone and in combination with eplerenone on the aldosterone hormone in the treatment of rats with experimentally induced heart failure

Background: High aldosterone levels contribute to kidney disease progression, while spironolactone in combination with ACEi or ARBs can potentially reduce proteinuria and ameliorate kidney function deterioration. However, evidence on the impact of eplerenone in patients with glomerulonephritis is scarce. Methods: In this prospective observational study, we assessed the effects of eplerenone in patients with biopsy-proven glomerulonephritis who were already treated with ACEi or ARBs. Patients received either eplerenone (25 mg daily) on top of ACEi or ARBs or standard treatment alone. Proteinuria (24 h total protein excretion), kidney function, blood pressure and serum K+ levels were assessed at 3, 6 and 12 months after the initiation of treatment. Results: Sixty-six patients were included in the study. Eplerenone was administered in 30 patients, while 36 received only ACEi or ARB. Proteinuria decreased from 1768 to 1152 mg/24 h after 1 year of eplerenone treatment, while it remained stable in controls. Eplerenone showed significant impact on proteinuria in those with baseline proteinuria of >1000 mg/24 h. Patients who received eplerenone showed a reduction in systolic blood pressure, while eGFR and serum K+ levels remained stable. Conclusions: Addition of eplerenone has a beneficial effect on proteinuria in patients with glomerulonephritis and significant baseline proteinuria. [ABSTRACT FROM AUTHOR]

Keywords: Phospholamban; Eplerenone; Fibrosis; Cardiomyopathy; Heart failure; Randomized clinical trial EN Phospholamban Eplerenone Fibrosis Cardiomyopathy Heart failure Randomized clinical trial 4284 4287 4 10/25/23 20231021 NES 231021 Introduction Phospholamban ( I PLN i ; p.Arg14del) cardiomyopathy is an inherited disease caused by the pathogenic p.Arg14del variant in the I PLN i gene. The phospholamban p.(Arg14del) pathogenic variant leads to cardiomyopathy with heart failure and is unresponsive to standard heart failure therapy. Future research into I PLN i p.Arg14del cardiomyopathy disease progression or modification - and more broadly, research into asymptomatic carriers of pathogenic variations associated with genetic cardiomyopathies - may be better designed using the knowledge obtained in this study. Phospholamban R14del mutation in patients diagnosed with dilated cardiomyopathy or arrhythmogenic right ventricular cardiomyopathy: evidence supporting the concept of arrhythmogenic cardiomyopathy. [Extracted from the article]

Decision-analytic models (DAMs) with varying structures and assumptions have been applied in economic evaluations (EEs) to assist decision making for heart failure with reduced ejection fraction (HFrEF) therapeutics. This systematic review aimed to summarize and critically appraise the EEs of guideline-directed medical therapies (GDMTs) for HFrEF. A systematic search of English articles and gray literature, published from January 2010, was performed on databases including MEDLINE, Embase, Scopus, NHSEED, health technology assessment, Cochrane Library, etc. The included studies were EEs with DAMs that compared the costs and outcomes of angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, angiotensin-receptor neprilysin inhibitors, beta-blockers, mineralocorticoid-receptor agonists, and sodium-glucose cotransporter-2 inhibitors. The study quality was evaluated using the Bias in Economic Evaluation (ECOBIAS) 2015 checklist and Consolidated Health Economic Evaluation Reporting Standards (CHEERS) 2022 checklists. A total of 59 EEs were included. Markov model, with a lifetime horizon and a monthly cycle length, was most commonly used in evaluating GDMTs for HFrEF. Most EEs conducted in the high-income countries demonstrated that novel GDMTs for HFrEF were cost-effective compared with the standard of care, with the standardized median incremental cost-effectiveness ratio (ICER) of $21 361/quality-adjusted life-year. The key factors influencing ICERs and study conclusions included model structures, input parameters, clinical heterogeneity, and country-specific willingness-to-pay threshold. Novel GDMTs were cost-effective compared with the standard of care. Given the heterogeneity of the DAMs and ICERs, alongside variations in willingness-to-pay thresholds across countries, there is a need to conduct country-specific EEs, particularly in low- and middle-income countries, using model structures that are coherent with the local decision context. • Consistent with previous review, Markov model was most commonly used in evaluating the cost-effectiveness of guideline-directed medical therapies for heart failure with reduced ejection population. • This study revealed that novel guideline-directed medical therapies for heart failure with reduced ejection (including sacubitril-valsartan, dapagliflozin, empagliflozin, and eplerenone) were cost-effective, particularly in high-income countries. • Given the heterogeneity of decision-analytic models and incremental cost-effectiveness ratios, alongside variations in willingness-to-pay thresholds across countries, there is a need to conduct country-specific economic evaluations, particularly in low- and middle-income countries, using model structures that are coherent with the local decision context. [ABSTRACT FROM AUTHOR]

Intraocular pressure (IOP) is the main modifiable risk factor for glaucoma. Current therapies target the anterior outflow of aqueous humor or its production. This study aims to demonstrate eplerenone could reduce IOP through a possible posterior outflow path via retinal pigment epithelium (RPE). Methods: In this retrospective study, IOP changes in patients undergoing eplerenone treatment were investigated. Inclusion criteria were IOP data immediately before and during treatment. Exclusion criteria included ophthalmic procedures, changes in topical glaucoma treatment, or taking systemic medications affecting IOP. After reviewing 162 charts, 41 subjects were eligible. Pearson correlation test was used to investigate the correlation between continuous IOP and eplerenone dosage. Results: The mean ± SD IOP before eplerenone treatment was 14.31 ± 3.73 mmHg and decreased to 13.50 ± 4.04 mmHg; however, this was not statistically significant (P = 0.39). In subset of patients with eplerenone dose of more than 25 mg/day and baseline IOP equal to or less than 15 mmHg, the mean IOP before eplerenone treatment was 12.33 ± 2.59 mmHg and decreased to 10.33 ± 2.99, which is a trend toward IOP reduction with a 16% reduction in IOP (P = 0.055). Conclusion: A possible dose-dependent decrease in IOP with eplerenone provides indirect evidence for the posterior flow model and suggests the mineralocorticoid receptors (MRs) in RPE play a role in the posterior flow of aqueous humor. It can be deduced that the RPE pumps responsible for the posterior flow of aqueous humor are MR-regulated and their function can be enhanced with MR antagonists. [ABSTRACT FROM AUTHOR]

Background and Aims To investigate the cardiovascular effects of sodium–glucose co-transporter-2 inhibitors (SGLT2i) with concomitant mineralocorticoid receptor antagonist (MRA) use in heart failure (HF) regardless of ejection fraction (EF) and explore the risk of MRA-associated adverse events in individuals randomized to SGLT2i vs. placebo. Methods PubMed/MEDLINE, Web of Science, Embase, and clinical trial registries were searched for randomized controlled trials/ post-hoc analyses evaluating SGLT2i in HF with or without MRA use (PROSPERO: CRD42023397129). The main outcomes were composite of first hospitalization or urgent visit for HF/cardiovascular death (HHF/CVD), HHF, and CVD. Others were all-cause mortality, composite renal and safety outcomes. Hazard ratios (HR)/risk ratios were extracted. Fixed-effects meta-analyses and subgroup analyses were performed. Results Five eligible studies were included, pooling data from 21 947 people with HF (type 2 diabetes mellitus, n = 10 805). Compared to placebo, randomization to SGLT2i showed a similar reduction in HHF/CVD and HHF in people who were or were not using MRAs [HHF/CVD: hazard ratio (HR) 0.75; 95% confidence interval (CI) 0.68–0.81 vs. HR 0.79; 95% CI 0.72–0.86; P -interaction =.43; HHF: HR 0.74; 95% CI 0.67–0.83 vs. HR 0.71; 95% CI 0.63–0.80; P -interaction =.53], with a suggestion of greater relative reduction in CVD in chronic HF people randomized to SGLT2i and using MRAs irrespective of EF (HR 0.81; 95% CI 0.72–0.91 vs. HR 0.98; 95% CI 0.86–1.13; P -interaction =.034). SGLT2i reduced all-cause mortality (P -interaction =.27) and adverse renal endpoints regardless of MRA use (P -interaction =.73) despite a higher risk of volume depletion with concomitant MRAs (P -interaction =.082). SGLT2i attenuated the risk of mild hyperkalaemia (P -interaction <.001) and severe hyperkalaemia (P -interaction =.051) associated with MRA use. Conclusions MRAs did not influence SGLT2i effects on the composite of HHF/CVD, HHF or all-cause mortality; however, findings hinted at a more pronounced relative reduction in CVD in chronic HF patients regardless of EF who were randomized to SGLT2i and receiving an MRA compared to those randomized to SGLT2i and not receiving MRAs. SGLT2i attenuated the risk of MRA-associated treatment-emergent hyperkalaemia. These findings warrant further validation in well-designed randomized controlled trials. [ABSTRACT FROM AUTHOR]