scholarly journals Advances in the Development of Non-steroidal Mineralocorticoid-receptor Antagonists

2019 ◽  
Author(s):  
Felipe L. Pérez-Gordillo ◽  
Maria Jesús Pérez de Vega ◽  
Guillermo Gerona-Navarro ◽  
Yoel Rodríguez ◽  
Diego Alvarez de la Rosa ◽  
...  
Keyword(s):  
Mineralocorticoid Receptor ◽  
Mineralocorticoid Receptor Antagonists ◽  
Receptor Antagonists

scholarly journals Mineralocorticoid receptor antagonists for nephroprotection and cardioprotection in patients with diabetes mellitus and chronic kidney disease

2021 ◽  
Author(s):  
Alberto Ortiz ◽  
Charles J Ferro ◽  
Olga Balafa ◽  
Michel Burnier ◽  
Robert Ekart ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Kidney Failure ◽  
Mineralocorticoid Receptor ◽  
Diabetic Kidney Disease ◽  
Renin Angiotensin System ◽  
Cardiovascular Death ◽  
Mineralocorticoid Receptor Antagonists ◽  
Receptor Antagonists ◽  
Diabetic Kidney

Abstract Diabetic kidney disease develops in about 40% of patients with diabetes and is the commonest cause of chronic kidney disease worldwide. Patients with chronic kidney disease, especially those with diabetes mellitus, are at high risk of both developing kidney failure and cardiovascular death. The use of renin-angiotensin system blockers to reduce the incidence of kidney failure in patients with diabetic kidney disease dates back to studies that are now 20 or more years old. During the last few years sodium-glucose co-transporter-2 inhibitors have shown beneficial renal effects in randomized trials. However, even in response to combined treatment with renin-angiotensin system blockers and sodium-glucose co-transporter-2 inhibitors, the renal residual risk remains high with kidney failure only deferred, but not avoided. The risk of cardiovascular death also remains high even with optimal current treatment. Steroidal mineralocorticoid receptor antagonists reduce albuminuria and surrogate markers of cardiovascular disease in patients already on optimal therapy. However, their use has been curtailed by the significant risk of hyperkalaemia. In The FInerenone in reducing kiDnEy faiLure and dIsease prOgression in Diabetic Kidney Disease (FIDELIO-DKD) study comparing the actions of the non-steroidal mineralocorticoid receptor antagonist finerenone with placebo, finerenone reduced the progression of diabetic kidney disease and the incidence of cardiovascular events with a relatively safe adverse event profile. This document presents in detail the available evidence on the cardioprotective and nephroprotective effects of mineralocorticoid receptor antagonists, analyses the potential mechanisms involved and discusses their potential future place in the treatment of patients with diabetic chronic kidney disease.

Cardiovascular Protection With Sodium-Glucose Cotransporter-2 Inhibitors and Mineralocorticoid Receptor Antagonists in Chronic Kidney Disease

Hypertension ◽  
2021 ◽  
Vol 77 (5) ◽  
pp. 1442-1455
Author(s):  
Pantelis Sarafidis ◽  
Christodoulos E. Papadopoulos ◽  
Vasilios Kamperidis ◽  
George Giannakoulas ◽  
Michael Doumas
Keyword(s):  
Risk Factors ◽  
Cardiovascular Disease ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Cardiovascular Events ◽  
Mineralocorticoid Receptor ◽  
Mineralocorticoid Receptor Antagonists ◽  
Receptor Antagonists ◽  
Cardiovascular Protection ◽  
Sodium Glucose Cotransporter

Chronic kidney disease (CKD) and cardiovascular disease are intimately linked. They share major risk factors, including age, hypertension, and diabetes, and common pathogenetic mechanisms. Furthermore, reduced renal function and kidney injury documented with albuminuria are independent risk factors for cardiovascular events and mortality. In major renal outcome trials and subsequent meta-analyses in patients with CKD, ACE (angiotensin-converting enzyme) inhibitors and ARBs (angiotensin II receptor blockers) were shown to effectively retard CKD progression but not to significantly reduce cardiovascular events or mortality. Thus, a high residual risk for cardiovascular disease progression under standard-of-care treatment is still present for patients with CKD. In contrast to the above, several outcome trials with SGLT-2 (sodium-glucose cotransporter-2) inhibitors and MRAs (mineralocorticoid receptor antagonists) clearly suggest that these agents, apart from nephroprotection, offer important cardioprotection in this population. This article discusses existing evidence on the effects of SGLT-2 inhibitors and MRAs on cardiovascular outcomes in patients with CKD that open new roads in cardiovascular protection of this heavily burdened population.

Abstract 040: Mineralocorticoid Receptor Antagonists After Hospitalization of Patients With Heart Failure With a Reduced Ejection Fraction

2017 ◽  
Vol 10 (suppl_3) ◽  
Author(s):  
Matthew S Durstenfeld ◽  
Stuart D Katz ◽  
Hannah Park ◽  
Saul Blecker
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Mineralocorticoid Receptor ◽  
Secondary Diagnosis ◽  
Mineralocorticoid Receptor Antagonists ◽  
Principal Diagnosis ◽  
Receptor Antagonists ◽  
Reduced Ejection Fraction ◽  
Patients With Heart Failure ◽  
Before And After

Background: Mineralocorticoid receptor antagonists (MRAs) are an important component of guideline-directed therapy for patients with heart failure with a reduced ejection fraction (HFrEF) but are underutilized in clinical practice. Hospitalization is a quality-improvement opportunity to increase appropriate use of MRAs, particularly as this therapy is associated with reduced readmission following both hospitalizations with a principal and secondary diagnosis of heart failure. We studied MRA prescription for heart failure patients before and after hospitalization. Methods: We performed a retrospective cohort study of adults hospitalized within an academic tertiary-care hospital system in 2013-2015 with a principal or secondary discharge diagnosis of heart failure. We included patients with ejection fraction ≤35%, systolic blood pressure ≥100 mm Hg, estimated glomerular filtration rate >30 ml/min/1.73 m 2 , and potassium <5.0 mEq/L. We recorded MRA prescription before and after hospitalization. We used McNemar’s test to compare MRA prescription before and after hospitalization, with pre-specified principal and secondary diagnosis subgroups. We used the chi-square test to compare prescriptions between groups. Results: Among 1176 hospitalizations of patients who met the inclusion criteria, the mean age was 72.7±13.4 years and 366 (31%) were female. Of these patients, 303 (25.8%) were prescribed MRAs prior to hospitalization and 331 (28.2%) were prescribed them at discharge, a small but statistically significant increase (p=0.02). Among patients previously prescribed MRAs, 241 (79.5%) continued them at discharge. Among 873 patients not previously prescribed MRAs, 90 (10.3%) had MRAs initiated at discharge. Among 347 patients with a principal diagnosis of heart failure, 95 had MRAs continued, 27 had MRAs discontinued, and 39 had MRAs initiated, a non-significant increase of 12 patients (+3.6%, p=0.14). Among 829 patients with a secondary diagnosis, 146 had MRAs continued, 35 had MRAs discontinued, and 51 had MRAs initiated, a non-significant increase of 16 patients (+1.9%, p=0.08). More patients with a principal diagnosis received MRAs at discharge: 134/347 (38.6%) compared to 197/829 (23.7%) patients discharged with a secondary diagnosis of HFrEF, p<0.0001; similarly, patients with a principal diagnosis of HFrEF had higher rates of MRA initiation at discharge: 39/225 (17.3%) versus 51/648 (7.9%), p=0.0004. Conclusions: Over 70% of hospitalized HFrEF patients did not receive MRAs before or after hospitalization. Although more patients with a principal diagnosis than secondary diagnosis of heart failure received MRAs and had them initiated, over 80% of eligible patients not on MRAs were not initiated on them at discharge. Hospitalization remains an opportunity to identify patients indicated for MRAs and initiate guideline-directed heart failure pharmacotherapy.

Non-steroidal mineralocorticoid receptor antagonists

2021 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Kristin Watson ◽  
Alina Kukin ◽  
Allie K Wasik ◽  
Christine E Shulenberger
Keyword(s):  
Mineralocorticoid Receptor ◽  
Mineralocorticoid Receptor Antagonists ◽  
Receptor Antagonists
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