Effect of Finerenone on chronic kidney disease outcomes in type 2 diabetes

Background: Finerenone, a nonsteroidal, selective mineralocorticoid receptor antagonist, reduced albuminuria in short-term trials involving patients with chronic kidney disease (CKD) and type 2 diabetes. However, its long-term effects on kidney and cardiovascular outcomes are unknown. Methods: In this double-blind trial, we randomly assigned 5734 patients with CKD and type 2 diabetes in a 1:1 ratio to receive finerenone or placebo. Eligible patients had a urinary albumin-to-creatinine ratio (with albumin measured in milligrams and creatinine measured in grams) of 30 to less than 300, an estimated glomerular filtration rate (eGFR) of 25 to less than 60 ml per minute per 1.73 m2 of body-surface area, and diabetic retinopathy, or they had a urinary albumin-to-creatinine ratio of 300 to 5000 and an eGFR of 25 to less than 75 ml per minute per 1.73 m2. All the patients were treated with renin-angiotensin system blockade that had been adjusted before randomization to the maximum dose on the manufacturer's label that did not cause unacceptable side effects. The primary composite outcome, assessed in a time-to-event analysis, was kidney failure, a sustained decrease of at least 40% in the eGFR from baseline, or death from renal causes. The key secondary composite outcome, also assessed in a time-to-event analysis, was death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Results: During a median follow-up of 2.6 years, a primary outcome event occurred in 504 of 2833 patients (17.8%) in the finerenone group and 600 of 2841 patients (21.1%) in the placebo group (hazard ratio, 0.82; 95% confidence interval [CI], 0.73 to 0.93; P = 0.001). A key secondary outcome event occurred in 367 patients (13.0%) and 420 patients (14.8%) in the respective groups (hazard ratio, 0.86; 95% CI, 0.75 to 0.99; P = 0.03). Overall, the frequency of adverse events was similar in the two groups. The incidence of hyperkalemia-related discontinuation of the trial regimen was higher with finerenone than with placebo (2.3% and 0.9%, respectively). Conclusions: In patients with CKD and type 2 diabetes, treatment with finerenone resulted in lower risks of CKD progression and cardiovascular events than placebo. (Funded by Bayer; FIDELIO-DKD ClinicalTrials.gov number, NCT02540993.)

Effect of finerenone on chronic kidney disease outcomes in type 2 diabetes

BACKGROUND Finerenone, a nonsteroidal, selective mineralocorticoid receptor antagonist, reduced albuminuria in short-term trials involving patients with chronic kidney disease (CKD) and type 2 diabetes. However, its long-term effects on kidney and cardiovascular outcomes are unknown. METHODS In this double-blind trial, we randomly assigned 5734 patients with CKD and type 2 diabetes in a 1:1 ratio to receive finerenone or placebo. Eligible patients had a urinary albumin-to-creatinine ratio (with albumin measured in milligrams and creatinine measured in grams) of 30 to less than 300, an estimated glomerular filtration rate (eGFR) of 25 to less than 60 ml per minute per 1.73 m2 of bodysurface area, and diabetic retinopathy, or they had a urinary albumin-to-creatinine ratio of 300 to 5000 and an eGFR of 25 to less than 75 ml per minute per 1.73 m2. All the patients were treated with renin-angiotensin system blockade that had been adjusted before randomization to the maximum dose on the manufacturer's label that did not cause unacceptable side effects. The primary composite outcome, assessed in a time-to-event analysis, was kidney failure, a sustained decrease of at least 40% in the eGFR from baseline, or death from renal causes. The key secondary composite outcome, also assessed in a time-to-event analysis, was death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. RESULTS During a median follow-up of 2.6 years, a primary outcome event occurred in 504 of 2833 patients (17.8%) in the finerenone group and 600 of 2841 patients (21.1%) in the placebo group (hazard ratio, 0.82; 95% confidence interval [CI], 0.73 to 0.93; P = 0.001). A key secondary outcome event occurred in 367 patients (13.0%) and 420 patients (14.8%) in the respective groups (hazard ratio, 0.86; 95% CI, 0.75 to 0.99; P = 0.03). Overall, the frequency of adverse events was similar in the two groups. The incidence of hyperkalemia-related discontinuation of the trial regimen was higher with finerenone than with placebo (2.3% and 0.9%, respectively). CONCLUSIONS In patients with CKD and type 2 diabetes, treatment with finerenone resulted in lower risks of CKD progression and cardiovascular events than placebo. Copyright © 2020 Massachusetts Medical Society

Design and Baseline Characteristics of the Finerenone in Reducing Kidney Failure and Disease Progression in Diabetic Kidney Disease Trial

BACKGROUND: Among diabetics, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality, and progression of their underlying disease. Finerenone is a novel, non-steroidal, selective mineralocorticoid-receptor antagonist which has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD), while revealing only a low risk of hyperkalemia. However, the effect of finerenone on renal and CV outcomes has not been investigated in long-term trials yet. METHODS: The Finerenone in Reducing Kidney Failure and Disease Progression in Diabetic Kidney Disease -(FIDELIO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important renal and CV outcomes in T2D patients with CKD. FIDELIO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 5.5 years. FIDELIO-DKD randomized 5,734 patients with an estimated glomerular filtration rate (eGFR) ≥25-<75 mL/min/1.73 m2 and albuminuria (urinary albumin-to-creatinine ratio ≥30-≤5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of primary outcome (overall two-sided significance level α = 0.05), the composite of time to first occurrence of kidney failure, a sustained decrease of eGFR ≥40% from baseline over at least 4 weeks, or renal death. CONCLUSION: FIDELIO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of renal and CV events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen.status: publishe

Finerenone and Chronic Kidney Disease Outcomes in Type 2 Diabetes

10.1056/nejmc2036175New England Journal of Medicine38411e42-e4

Outcomes with Finerenone in Participants with Stage 4 CKD and Type 2 Diabetes: A FIDELITY Subgroup Analysis.

Background Patients with stage 4 chronic kidney disease (CKD) and type 2 diabetes have limited treatment options to reduce their persistent cardiovascular and kidney risk. In FIDELITY, a prespecified pooled analysis of FIDELIO-DKD and FIGARO-DKD, finerenone improved heart-kidney outcomes in participants with CKD and type 2 diabetes. Methods This FIDELITY subgroup analysis investigated the effects of finerenone in participants with stage 4 CKD (estimated glomerular filtration rate [eGFR]/min/1.73 m2). Efficacy outcomes included a cardiovascular composite (cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure) and a kidney composite (kidney failure, sustained ≥57% decrease in eGFR from baseline, or kidney disease death). Results Of 13,023 participants, 890 (7%) had stage 4 CKD. The hazard ratio for risk of cardiovascular composite outcome with finerenone versus placebo was 0.78 (95% confidence interval 0.57-1.07). The kidney composite outcome proportional hazards assumption was not met for the overall study period, with a protective effect only shown up to 2 years, after which the direction of association was inconsistent and an observed loss of precision over time incurred on finerenone versus placebo risk differences. Nonetheless, albuminuria and rate of eGFR decline were consistently reduced with finerenone versus placebo. Adverse events were balanced between treatment arms. Hyperkalemia was the most common AE reported (stage 4 CKD: 26% and 13% for finerenone versus placebo, respectively) however, the incidence of hyperkalemia leading to permanent discontinuation was low (stage 4 CKD: 3% and 2% for finerenone versus placebo, respectively). Conclusions The cardiovascular benefits and safety profile of finerenone in participants with stage 4 CKD were consistent with the overall FIDELITY population; this was also the case for albuminuria and the rate of eGFR decline. The effects on the composite kidney outcome were not consistent over time

Finerenone Reduces Onset of Atrial Fibrillation in Patients with Chronic Kidney Disease and Type 2 Diabetes

Background Patients with chronic kidney disease (CKD) and type 2 diabetes (T2D) are at risk of atrial fibrillation or flutter (AFF) due to cardiac remodeling and kidney complications. Finerenone, a novel, selective, nonsteroidal mineralocorticoid receptor antagonist, inhibited cardiac remodeling in preclinical models. Objectives To examine the effect of finerenone on new-onset AFF and cardiorenal effects by history of AFF in FIDELIO-DKD. Methods Patients with CKD and T2D were randomized (1:1) to finerenone or placebo. Eligible patients had a urine albumin-to-creatinine ratio ≥30 to ≤5,000 mg/g, an estimated glomerular filtration rate (eGFR) ≥25 to <75 ml/min/1.73 m2 and received optimized doses of renin–angiotensin system blockade. Effect on new-onset AFF was evaluated as a prespecified outcome adjudicated by an independent cardiologist committee. The primary composite outcome (kidney failure, sustained ≥40% decrease in eGFR from baseline, or renal death) and key secondary outcome (cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure) were analyzed by history of AFF. Results Of 5,674 patients, 461 (8.1%) had a history of AFF. New-onset AFF occurred in 82 (3.2%) patients on finerenone and 117 (4.5%) on placebo (hazard ratio: 0.71; 95% confidence interval: 0.53 to 0.94; p = 0.016). The effect of finerenone on primary and key secondary kidney and cardiovascular outcomes was not significantly impacted by baseline AFF (interaction p value: 0.16 and 0.85, respectively). Conclusions In patients with CKD and T2D, finerenone reduced the risk of new-onset AFF. The risk of kidney or cardiovascular events was reduced irrespective of history of AFF at baseline.Sin financiación20.589 JCR (2019) Q1, 3/138 Cardiac & Cardiovascular Systems10.315 SJR (2020) Q1, 1/349 Cardiology and Cardiovascular MedicineNo data IDR 2019UE

Efficacy and safety of finerenone in patients with chronic kidney disease and type 2 diabetes by GLP-1RA treatment: A subgroup analysis from the FIDELIO-DKD trial

Aims Finerenone significantly reduced the risk of kidney and cardiovascular (CV) outcomes in patients with chronic kidney disease and type 2 diabetes in the FIDELIO-DKD trial (NCT02540993). This exploratory subgroup analysis investigates the effect of glucagon-like peptide-1 receptor agonist (GLP-1RA) use on the treatment effect of finerenone. Materials and Methods Patients with type 2 diabetes, urine albumin-to-creatinine ratio (UACR) 30-5000 mg/g and estimated glomerular filtration rate 25- Of the 5674 patients analysed, overall, 394 (6.9%) received GLP-1RAs at baseline. A reduction in UACR with finerenone was observed with or without baseline GLP-1RA use; ratio of least-squares means 0.63 (95% confidence interval 0.56, 0.70) with GLP-1RA use and 0.69 (95% confidence interval 0.67, 0.72) without GLP-1RA use (p value for interaction .20). Finerenone also significantly reduced the primary kidney (time to kidney failure, sustained decrease in estimated glomerular filtration rate &gt;= 40% from baseline, or renal death) and key secondary CV outcomes (time to CV death, non-fatal myocardial infarction, non-fatal stroke, or hospitalization for heart failure) versus placebo, with no clear difference because of GLP-1RA use at baseline (p value for interaction .15 and .51 respectively) or any time during the trial. The safety profile of finerenone was similar between subgroups. Conclusions This exploratory subgroup analysis suggests that finerenone reduces UACR in patients with or without GLP-1RA use at baseline, and the effects on kidney and CV outcomes are consistent irrespective of GLP-1RA use

Finerenone Reduces New-Onset Atrial Fibrillation in Patients With Chronic Kidney Disease and Type 2 Diabetes

BACKGROUND Patients with chronic kidney disease (CKD) and type 2 diabetes (T2D) are at risk of atrial fibrillation or flutter (AFF) due to cardiac remodeling and kidney complications. Finerenone, a novel, selective, nonsteroidal mineralocorticoid receptor antagonist, inhibited cardiac remodeling in preclinical models. OBJECTIVES This work aims to examine the effect of finerenone on new-onset AFF and cardiorenal effects by history of AFF in the Finerenone in Reducing Kidney Failure and Disease Progression in Diabetic Kidney Disease (FIDELIO-DKD) study. METHODS Patients with CKD and T2D were randomized (1:1) to finerenone or placebo. Eligible patients had a urine albumin-to-creatinine ratio &gt;= 30 to &lt;= 5,000 mg/g, an estimated glomerular filtration rate (eGFR) &gt;= 25 to &lt;75 ml/min/1.73 m(2) and received optimized doses of renin-angiotensin system blockade. Effect on new-onset AFF was evaluated as a pre-specified outcome adjudicated by an independent cardiologist committee. The primary composite outcome (time to first onset of kidney failure, a sustained decrease of &gt;= 40% in eGFR from baseline, or death from renal causes) and key secondary outcome (time to first onset of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure) were analyzed by history of AFF. RESULTS Of 5,674 patients, 461 (8.1%) had a history of AFF. New-onset AFF occurred in 82 (3.2%) patients on finerenone and 117 (4.5%) patients on placebo (hazard ratio: 0.71; 95% confidence interval: 0.53-0.94; p = 0.016). The effect of finerenone on primary and key secondary kidney and cardiovascular outcomes was not significantly impacted by baseline AFF (interaction p value: 0.16 and 0.85, respectively). CONCLUSIONS In patients with CKD and T2D, finerenone reduced the risk of new-onset AFF. The risk of kidney or cardiovascular events was reduced irrespective of history of AFF at baseline. (EudraCT 2015-000990-11 [A randomized, double-blind, placebo-controlled, parallel-group, multicenter, event-driven Phase III study to investigate the efficacy and safety of finerenone, in addition to standard of care, on the progression of kidney disease in subjects with type 2 diabetes mellitus and the clinical diagnosis of diabetic kidney disease]; Efficacy and Safety of Finerenone in Subjects With Type 2 Diabetes Mellitus and Diabetic Kidney Disease [FIDELIO-DKD]; NCT02540993)((C) 2021 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation.