We aim to review the mechanism of action and safety profile of mineralocorticoid receptor antagonists (MRAs) and discuss the differences between selective and non-selective MRAs. More specifically, finerenone is a new medication that is currently under investigation for its promising cardiovascular and nephrological effects. MRAs are well known for their utility in treating heart failure, refractory hypertension, and diverse nephropathies, namely, diabetic nephropathy. As their name denotes, MRAs inhibit the action of aldosterone at the mineralocorticoid receptor, preventing receptor activation. This prevents remodeling, decreases inflammation, and improves proteinuria. There are not significant differences in outcomes between selective and non-selective MRAs. A new selective MRA named finerenone (originally BAY 94-8862) has shown promising results in several trials (ARTS-HF and ARTS-DN) and smaller studies. Finerenone may have a dose-dependent benefit over older MRAs, decreasing rates of albuminuria and levels of BNP and NT-ProBNP without causing a significant increase in serum potassium levels. This medication is not yet approved as it is still in phase 3 clinical trials (FIGARO-DKD and FIDELIO-DKD trials). MRAs are beneficial in several disease states. Newer medications, such as finerenone, should be considered in patients with heart failure and diabetic nephropathy who may benefit from a reduction in albuminuria and BNP/NT-ProBNP. Data surrounding finerenone are limited to date. However, results from ongoing clinical trials, as well as new trials to evaluate use in other pathologies, could validate the implementation of this medication in daily practice.

Mineralocorticoid Receptor Antagonists: a Comprehensive Review of Finerenone

Aldosterone binds to the mineralocorticoid receptor (MR), a transcription factor of the nuclear receptor family, present in the kidney and in various other non-epithelial cells including the heart and the vasculature (Cannavo et al., 2018). Indeed, extra-renal pathophysiological effects of this hormone have been characterized, extending its actions to the cardiovascular (CV) system (Messaoudi et al., 2012). A growing body of clinical and pre-clinical evidence suggests that MR overactivation plays an important pathophysiological role in CV remodeling by promoting cardiac hypertrophy, fibrosis, arterial stiffness, as well as in inflammation and oxidative stress (Bauersachs et al., 2015). The following review article outlines the role of MR in CV disease with a focus on myocardial remodeling and heart failure (HF) including clinical trials as well as cellular and animal studies.

/pdf/mineralocorticoid-receptor-in-cardiovascular-diseases-1yw7bcuo1n.pdf

Mineralocorticoid receptor in cardiovascular diseases-Clinical trials and mechanistic insights.

Chronic kidney diseases (CKD) and cardiovascular diseases (CVD) are the main complications in type 2 diabetic mellitus (T2DM), increasing the risk of cardiovascular and all-cause mortality. Current therapeutic strategies that delay the progression of CKD and the development of CVD include angiotensin-converting enzyme inhibitors (ACEI), angiotensin II receptor blockers (ARB), sodium-glucose co-transporter 2 inhibitors (SGLT-2i) and GLP-1 receptor agonists (GLP-1RA). In the progression of CKD and CVD, mineralocorticoid receptor (MR) overactivation leads to inflammation and fibrosis in the heart, kidney and vascular system, making mineralocorticoid receptor antagonists (MRAs) as a promising therapeutic option in T2DM with CKD and CVD. Finerenone is the third generation highly selective non-steroidal MRAs. It significantly reduces the risk of cardiovascular and renal complications. Finerenone also improves the cardiovascular-renal outcomes in T2DM patients with CKD and/or chronic heart failure (CHF). It is safer and more effective than the first- and second-generation MRAs due to its higher selectivity and specificity, resulting in a lower incidence of adverse effects including hyperkalemia, renal insufficiency and androgen-like effects. Finerenone shows potent effect on improving the outcomes of CHF, refractory hypertension, and diabetic nephropathy. Recently studies have shown that finerenone may have potential therapeutic effect on diabetic retinopathy, primary aldosteronism, atrial fibrillation, pulmonary hypertension and so on. In this review, we discuss the characteristics of finerenone, the new third-generation MRA, and compared with the first- and second-generation steroidal MRAs and other nonsteroidal MRAs. We also focus on its safety and efficacy of clinical application on CKD with T2DM patients. We hope to provide new insights for the clinical application and therapeutic prospect.

https://www.frontiersin.org/articles/10.3389/fendo.2023.1125693/pdf

Cardiovascular-renal protective effect and molecular mechanism of finerenone in type 2 diabetic mellitus

Background Hypertension is a prevalent cardiovascular complication caused by genetic and nongenetic factors. Blood pressure (BP) management is difficult because most patients become resistant to monotherapy soon after treatment initiation. Although many antihypertensive drugs are available, some patients do not respond to multiple drugs. Identification of personalized antihypertensive treatments is a key for better BP management. Objective This review aimed to elucidate aspects of rational drug design and other methods to develop better hypertension management. Results Among hypertension-related signaling mechanisms, the renin-angiotensin-aldosterone system is the leading genetic target for hypertension treatment. Identifying a single drug that acts on multiple targets is an emerging strategy for hypertension treatment, and could be achieved by discovering new drug targets with less mutated and highly conserved regions. Extending pharmacogenomics research to include patients with hypertension receiving multiple antihypertensive drugs could help identify the genetic markers of hypertension. However, available evidence on the role of pharmacogenomics in hypertension is limited and primarily focused on candidate genes. Studies on hypertension pharmacogenomics aim to identify the genetic causes of response variations to antihypertensive drugs. Genetic association studies have identified single nucleotide polymorphisms affecting drug responses. To understand how genetic traits alter drug responses, computational screening of mutagenesis can be utilized to observe drug response variations at the protein level, which can help identify new inhibitors and drug targets to manage hypertension. Conclusion Rational drug design facilitates the discovery and design of potent inhibitors. However, further research and clinical validation are required before novel inhibitors can be clinically used as antihypertensive therapies.

Computational and Pharmacogenomic Insights on Hypertension Treatment: Rational Drug Design and Optimization Strategies

Aim The aim of this study was to evaluate the effects of canrenone compared to hydrochlorothiazide (HCTZ) added to angiotensin II receptor blockers (ARBs) on glycemia, lipid profile, potassium, aldosterone and renal function in patients with hypertension and type 2 diabetes mellitus. Patients and methods The study enrolled 182 Caucasian patients with hypertension and type 2 diabetes mellitus. Patients were already taking ARBs and were randomized to canrenone, 50 mg once a day, or HCTZ, 12.5 mg once a day for 1 month. After the first month, patients not reaching an adequate blood pressure (BP) were up-titrated to canrenone 100 mg or HCTZ 25 mg once a day for 12 months. The following parameters were considered at 6 and 12 months: BP, body weight, body mass index (BMI), fasting plasma glucose (FPG), post-prandial glucose (PPG), fasting plasma insulin (FPI), homeostasis model assessment insulin (HOMA-IR), lipid profile, potassium, plasma aldosterone, urine albumin excretion rate and estimated glomerular filtration rate (eGFR). Results We observed a similar decrease in BP with both treatments. Canrenone led to a significant decrease in FPG, PPG and HOMA index compared to baseline, while there was a significant increase in the same parameters with HCTZ. HCTZ also worsened glycated hemoglobin (HbA1c), while canrenone did not change it. No variations in lipid profile were recorded with canrenone, while there was a worsening of total cholesterol (TC) and triglycerides (Tg) with HCTZ. Potassium levels were decreased and uric acid levels were increased by HCTZ, but not by canrenone that had a neutral effect on these parameters. We recorded a slight decrease in eGFR with HCTZ and an improvement with canrenone; creatinine and eGFR were improved by canrenone compared to HCTZ. Plasma aldosterone levels were decreased by canrenone and increased by HCTZ. Conclusion Canrenone and HCTZ have a similar effect on BP; however, canrenone seems to improve metabolic parameters, while HCTZ worsens them.

/pdf/a-randomized-double-blind-clinical-trial-of-canrenone-vs-vafgqmdi92.pdf

A randomized, double-blind clinical trial of canrenone vs hydrochlorothiazide in addition to angiotensin II receptor blockers in hypertensive type 2 diabetic patients.

SummaryAim
To evaluate the effects of canrenone as add-on therapy in patients already treated with angiotensin-converting enzyme inhibitors (ACE-I) or angiotensin II receptor blockers (ARBs) and hydrochlorothiazide at the maximum dosage (25 mg/d).

Method
In this randomized, open-label, controlled trial, we enrolled 175 Caucasian patients with essential hypertension not well controlled by concomitant ACE-I or ARBs and hydrochlorothiazide. At baseline, 87 patients (57 males and 30 females) were randomized to add canrenone 50 mg, and 88 (56 males and 32 females) patients to canrenone 100 mg, once a day, for 3 months. At baseline and after 3 months, we evaluated blood pressure (BP), pulse pressure (PP), heart rate (HR), fasting plasma glucose (FPG), homeostasis model assessment insulin (HOMA Index), lipid profile, electrolytes, uric acid, estimated glomerular filtration rate (eGFR), plasma urea, aldosterone, B-type natriuretic peptide (BNP), and galectin-3.

Results
Blood pressure decreased with both dosages of canrenone, with a better effect with canrenone 100 mg (−20.26 vs −23.68 mm Hg for SBP, and −10.58 vs −12.38 mm Hg for DBP), without a clinically relevant increase in potassium levels. We did not observe any differences regarding FPG or HOMA Index, nor of lipid profile, with the exception of triglycerides, which increased compared to baseline with canrenone 50 mg (+0.25 vs +0.34 mEq/L). Creatinine slightly increased with canrenone 100 mg (+0.02 vs +0.05 mg/dL), although no variations of eGFR were observed in neither groups. There was an increase in aldosterone levels with canrenone 50 mg. No changes in BNP or galectin-3 were recorded.

Conclusion
Both canrenone dosages gave a decrease in blood pressure, with a better effect with the higher dose, with only a slight increase in potassium and creatinine levels, which were not clinically relevant. Clinical Trials Registration Eudract number: 2010-023606-13; ClinicalTrials.gov NCT02687178.

Efficacy and safety of two dosages of canrenone as add-on therapy in hypertensive patients taking ace-inhibitors or angiotensin II receptor blockers and hydrochlorothiazide at maximum dosage in a randomized clinical trial: The ESCAPE-IT trial.

BACKGROUND Blockade of the renin-angiotensin-aldosterone system is a cornerstone in cardiovascular disease prevention and hypertension treatment. The relevance of ambulatory blood pressure monitoring (ABPM) has been widely confirmed for both increasing the accuracy of blood pressure (BP) measurements, particularly in pharmacological trials, and focusing on 24 h BP prognostic parameters. The aim of this study was to assess the effects of canrenone addition on ambulatory BP in uncontrolled hypertensive patients already treated with the highest tolerated dose of angiotensin-converting enzyme (ACE) inhibitors or angiotensin II type 1 receptor (AT1R) antagonists plus hydrochlorothiazide (HCT). METHODS ABPM was performed at baseline and after 3 months of combination therapy in 158 outpatients with stage 1 or 2 hypertension who were randomized to add canrenone (50 or 100 mg) to the pre-existing therapy with ACE inhibitors or AT1R antagonists plus HCT. Twenty-four-hour systolic and diastolic BPs were considered normalized when the values were 10% with respect to diurnal values did not change during combination therapy. CONCLUSION Canrenone addition to ACE inhibitors or AT1R antagonists plus HCT was associated with a significant reduction of 24 h BP and to an increased number of patients meeting 24 h ABPM targets in a clinical setting of uncontrolled stage 1 or 2 hypertension.

/pdf/ambulatory-blood-pressure-parameters-after-canrenone-dc69ys26bd.pdf

Ambulatory blood pressure parameters after canrenone addition to existing treatment regimens with maximum tolerated dose of angiotensin-converting enzyme inhibitors/angiotensin II type 1 receptor blockers plus hydrochlorothiazide in uncontrolled hypertensive patients

Canrenone on cardiovascular mortality in congestive heart failure: CanrenOne eFFects on cardiovascular mortality in patiEnts with congEstIve hearT failure: The COFFEE-IT study.

Handle everyday research tasks with reliable, citation-backed results

Your personal Research Agent to handle research tasks with citation-backed results

Popular Tasks used by Researchers

How can I help with your research?

Meet SciSpace

Get more enhanced response by uploading the PDFs you want me to reference.

No relevant PDFs in your library

SciSpace is the AI research assistant for academics. Run systematic literature reviews on 280M+ papers, and write papers with cited sources. Trusted by 1M+ students, PhDs & researchers.

SciSpace | AI for Research

Analyze PDFs

Code & Manuscripts

Funding & Grants

Literature & Patents

Medical & Clinical Data

Systematic Review

Visualize & Present

Web & Data

Build a Google Scholar-like website for your research.

Build a website

Create charts and images for your research

Create a Chart

Write a paper for submission to a journal

Draft a manuscript

Patent Search

Design eye-catching scientific posters in minutes.

Scientific Poster Generation

Systematic Literature Review

One task is running at the moment. Your messages will be shown right after.

Drag and drop or click here to browse

Loved by <highlight>1 million+</highlight> researchers

Extract a list of specific topics and their sources from unstructured text

Topics

Compare and analyze relevant papers that matches with your search

Papers

Get insights from PDFs and bookmarked papers from your library

My library

Recent searches

Try searching for:

Catch AI-generated content in scholarly and non-scholarly content

{ai} Detector

Ai Writer

Get PDF Summaries, highlighted text explanations 

Chat with PDF

Effortlessly create in-text citations and bibliographies in APA and 2,500 other formats

Citation generator

Get explanations, summaries, and answers on academic papers

Ease up your research workflow with {scispace}'s cohort of exciting AI tools

Elevate your academic writing skills and convey your ideas the way you want

Paraphraser

Explore our range of reading and writing tools

Your file is being prepared and should be ready in a few minutes. If it's a large file, it might take a bit longer. You can close this window, and we'll email you the file when it's done.

You have reached a maximum limit of <strong>{limit}</strong> columns in the table. Remove at least <strong>1</strong> column to add or create another one.

Massimo Vanasia

Author Tools

Chat about Author

Papers

Efficacy and safety of two dosages of canrenone as add-on therapy in hypertensive patients taking ace-inhibitors or angiotensin II receptor blockers and hydrochlorothiazide at maximum dosage in a randomized clinical trial: The ESCAPE-IT trial.

Ambulatory blood pressure parameters after canrenone addition to existing treatment regimens with maximum tolerated dose of angiotensin-converting enzyme inhibitors/angiotensin II type 1 receptor blockers plus hydrochlorothiazide in uncontrolled hypertensive patients

Canrenone on cardiovascular mortality in congestive heart failure: CanrenOne eFFects on cardiovascular mortality in patiEnts with congEstIve hearT failure: The COFFEE-IT study.