Search

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]

• The ATHENA-HF clinical trial did not find additional decongestive benefit of spironolactone 100 mg/day for 96 hours in acute heart failure. • We performed a post hoc analysis of whether this spironolactone dosage had any pharmacodynamic effects. • We found that increased spironolactone dosing limited potassium losses in acute heart failure treatment and reduced the need for potassium replacement. • However, patients with acute heart failure and lower serum potassium levels did not experience greater decongestion with this intervention. The ATHENA-HF (Aldosterone Targeted Neurohormonal Combined with Natriuresis Therapy in Heart Failure) clinical trial found no improvements in natriuretic peptide levels or clinical congestion when spironolactone 100 mg/day for 96 hours was used in addition to usual treatment for acute heart failure. We performed a post hoc analysis of ATHENA-HF to determine whether spironolactone treatment induced any detectable pharmacodynamic effects and whether patients with potentially greater aldosterone activity experienced additional decongestion. Trial subjects previously treated with spironolactone were excluded. We first examined for changes in renal potassium handling. Using the baseline serum potassium level as a surrogate marker of spironolactone activity, we then divided each treatment arm into tertiles of baseline serum potassium and explored for differences in laboratory and clinical congestion outcomes. Among spironolactone-naïve patients, the change in serum potassium did not differ after 24 hours or 48 hours but was significantly greater with spironolactone treatment compared to placebo at 72 hours (0.23 ± 0.55 vs 0.03 ± 0.60 mEq/L; P = 0.042) and 96 hours (0.32 ± 0.51 vs 0.13 ± 0.72 mEq/L; P = 0.046). Potassium supplementation was similar at treatment start and at 24 hours, but spironolactone-treated patients required substantially less potassium replacement at 48 hours (24% vs 36%; P = 0.048), 72 hours (21% vs 37%; P = 0.013), and 96 hours (11% vs 38%; P < 0.001). When the treatment arms were divided into tertiles of baseline serum potassium, there were no differences in the 96-hour log N-terminal pro-B-type natriuretic peptide levels, net fluid loss, urine output, or dyspnea relief in any of the potassium groups, with no effect modification by treatment exposure. Spironolactone 100 mg/day for 96 hours in patients receiving intravenous loop diuresis for acute heart failure has no clear added decongestive ability but does meaningfully limit potassium wasting. [ABSTRACT FROM AUTHOR]

Overactivation of mineralocorticoid receptors occurs in cardiorenal diseases. Many patients with type 2 diabetes often progress to chronic kidney disease (CKD) and require dialysis. Finerenone is the first oral non-steroidal mineralocorticoid receptor antagonist used in patients with diabetic kidney disease and heart failure. Finerenone (Kerendia®) is more potent than spironolactone in reducing inflammation and fibrosis in CKD and exerts its effect equally on the heart and kidneys, improving cardiovascular outcomes. Research demonstrates that finerenone improves proteinuria and glomerular filtration rate if taken alone or in combination with sodium-glucose transporter 2 inhibitors. Finerenone has been found to decrease mortality in patients with diabetic renal disease and improve quality of life. Its side effects, unlike those of spironolactone, do not include gynecomastia. However, it can result in hyperkalemia, which needs to be monitored. In this review, we aim to investigate the mechanisms of action of finerenone and its implications in patients with type 2 diabetes. [ABSTRACT FROM AUTHOR]

Background: Spironolactone (SPL) is an effective treatment for women acne, but other effects on skin biophysical properties remain to be investigated. Objective s : The aim of the current study was to explore the effects of oral SPL used to treat women acne on skin biophysical properties, including hydration, transepidermal water loss (TEWL), skin surface lipid (SSL) levels, mechanical properties, color, pH, and pore size. Materials and Methods: Twenty‐five Thai women with acne treated with oral SPL were followed for 6 months. Skin hydration, TEWL, SSL levels, mechanical properties, color, pH, and pore size of the forehead, chest, and inner arm were evaluated at baseline and 2, 4, and 6 months after treatment with oral SPL. Facial and upper back pore size were also assessed. Clinical outcomes were changes in these skin biophysical properties at each visit compared with baseline. Results: Skin hydration, TEWL, SSL levels, color, pH, and pore size remained stable throughout the study. Facial skin parameters at 6 months demonstrated the following changes: hydration levels, 7.60 (95% confidence interval [CI], −59.74 to 74.94); TEWL, −2.36 (95% CI, −5.77 to 1.06); L* value, 0.51 (95% CI, −0.70 to 1.72); individual typology angle, 1.65 (95% CI −2.27 to 5.57); pH, 0.01 (95% CI −0.43 to 0.46); pore size, −0.24 (95% CI, −1.21 to 0.73); and SSL levels, 7.60 (95% CI −59.74 to 74.94). Improvement of facial mechanical properties was observed. R0 (indicating skin tightness) and R1 (indicating elasticity) showed significant decreases (−0.076 [95% CI, −0.141 to −0.010] and −0.016 [95% CI, −0.033 to −0.001]). R3 and R4 (representing tiring effects) were also improved (−0.091 [95% CI, −0.158 to −0.025] and −0.022 [95% CI, −0.044 to −0.001]). Parameters in the truncal and inner arm areas remained stable, except for skin elasticity and tiring effects, which exhibited a similar trend of improvement as the facial area. The changes were notable as early as 4 months. Conclusion: Oral SPL used for acne did not impair the skin barrier. Moreover, the skin mechanical properties were improved at 4 to 6 months. [ABSTRACT FROM AUTHOR]

Myocardial infarction (MI) is a type of cardiovascular disease that influences millions of human beings worldwide and has a great rate of mortality and morbidity. Spironolactone has been used as a critical drug for the treatment of cardiac failure and it ameliorates cardiac dysfunction post-MI. Despite these findings, whether there is a relationship between the therapeutic effects of spironolactone and the gut microorganism after MI has not been determined. In our research, we used male C57BL/6 J mice to explore whether the gut microbiota mediates the beneficial function of spironolactone after myocardial infarction. We demonstrated that deletion of the gut microbiota eliminated the beneficial function of spironolactone in MI mice, displaying exacerbated cardiac dysfunction, cardiac infarct size. In addition, the gut microbiota was altered by spironolactone after sham or MI operation in mice. We also used male C57BL/6 J mice to investigate the function of a probiotic in the myocardial infarction. In summary, our findings reveal a precious role of the gut flora in the therapeutic function of spironolactone on MI. [ABSTRACT FROM AUTHOR]

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]

Aims: The aim of the study was to implement a quality improvement project using the Lean Six Sigma framework of Define, Measure, Analyze, Improve, and Control in an outpatient urban medical dermatology clinic; educate providers about polycystic ovarian syndrome; increase endocrinology referrals; and optimize spironolactone use in these patients ages 12–45 years old. Background: Patients with polycystic ovarian syndrome experience delays in endocrinology referrals and often suboptimally treated with spironolactone because of lack of provider understanding. Method: Lean Six Sigma was used to increase provider ability to diagnose and manage polycystic ovarian syndrome, improve spironolactone dosing, and increase endocrinology referral rates through education. Pre-intervention collection occurred July to September 2023. Intervention occurred from September to December 2023. Post-intervention occurred December 2023 to February 2024. Provider surveys were collected through Microsoft Forms, and endocrinology referral rates were collected through the electronic health record, Epic. Results: Improved provider understanding of polycystic ovarian syndrome was demonstrated in survey results for rate of recognition, confidence, and awareness of diagnostic criteria. Referral rates increased by 90% via SlicerDicer tool within Epic. Conclusion: Through further education, dermatology providers can improve identification of the polycystic ovarian syndrome, patient outcomes, and patient experience. With identification of the need in this department, there is a platform to incorporate a multidisciplinary clinic. [ABSTRACT FROM AUTHOR]

Introduction: Uncontrolled hypertension is the leading risk factor for global mortality. Most hypertensive patients can be controlled with standard medication combinations, but some may not respond adequately to ≥3 or even to ≥5 antihypertensive agents. Areas covered: In this review, we summarize the recent literature on difficult-to-treat hypertension identified by a Medline search, and we discuss the options for fourth line and subsequent therapy. Expert opinion: It is essential to confirm resistant hypertension with out-of-office blood pressure measurements and to consider lifestyle factors, adherence to medication and secondary causes of hypertension. When true resistant hypertension is confirmed and blood pressure is not controlled with an optimal triple combination, preferably as a fixed dose combination tablet, spironolactone is usually recommended as the fourth medication. Comorbid conditions should be treated as appropriate with sodium-glucose-cotransporter 2 inhibitors, glucagon-like peptide-1 receptor agonists, sacubitril-valsartan or finerenone. Renal denervation appears to be a useful addition to overcome some of the problems of medication adherence. The endothelin antagonist aprocitentan may be a final option in some countries. Of the drugs in development, the RNA based therapeutics that inhibit angiotensinogen synthesis appear to be some of the most promising. [ABSTRACT FROM AUTHOR]

Diogo Pazzini Bomfim,1 Marco Alexandre Dias da Rocha,2 Adriana Sanudo,3 Edileia Bagatin2 1Translational Medicine, Federal University of Sao Paulo (UNIFESP), Sao Paulo, Brazil; 2Department of Dermatology, Federal University of Sao Paulo (UNIFESP), Sao Paulo, Brazil; 3Department of Preventive medicine, Federal University of Sao Paulo (UNIFESP), Sao Paulo, BrazilCorrespondence: Diogo Pazzini Bomfim, Email pazzini.bomfim@unifesp.brIntroduction: In several countries, recent research has shown an increase in the prevalence of adult female acne (AFA), defined as the acne that appears in women aged over 25. This disease brings some particularities and challenges, such as a greater impact on quality of life (QoL) and chronicity. A negative impact on QoL has been observed, as well as anxiety, depression, anger, low self-esteem, and feelings of embarrassment and frustration.Purpose: To quantify AFA’s impact on QoL and the influence of two dermatological treatments.Material and Methods: A prospective study including 40 women, aging from 25 to 44 years old, with mild-to-moderate acne was conducted. Participants underwent clinical, laboratory, and photographic evaluations. They were randomized into two treatment groups: group 1 – azelaic acid (AZA) 15% gel twice daily; group 2 – spironolactone (SPIRO) 100 mg/day and treated for 6 months. At baseline and at the end of treatments, a specific QoL questionnaire for acne, already translated and validated for Brazilian Portuguese (Acne-QoL-BR), was applied. It contains 19 questions allotted in four domains. Each item within a domain is scored from 0 to 6. The total score ranges from 0 to 114 and domains are distributed as follows: 0– 30 (self-perception), 0– 30 (role-emotional), 0– 24 (role-social), 0– 30 (acne-symptoms). Higher scores reflect better QoL.Results: The mean age was 32.7 (SD: 5.42); 85% presented persistent acne. After treatment regardless of group, there was a significant improvement in total score and all domains’ scores of acne QoL-BR (p < 0.001), with no difference between groups, despite one treatment being topical and the other systemic (p=0.918).Conclusion: Acne-QoL-BR is a useful tool for quantifying the impact of acne and should be used as an efficacy parameter in clinical trials.Keywords: adult female acne, quality of life, azelaic acid, spironolactone

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