Finerenone and Cardiovascular Outcomes in Patients With Chronic Kidney Disease and Type 2 Diabetes

Abstract

Background: The FIDELIO-DKD trial evaluated the effect of the nonsteroidal, selective mineralocorticoid receptor antagonist finerenone on kidney and cardiovascular (CV) outcomes in patients with chronic kidney disease (CKD) and type 2 diabetes (T2D) with optimized renin-angiotensin system blockade. Compared with placebo, finerenone reduced the composite kidney and CV outcomes. We report the effect of finerenone on individual CV outcomes and in patients with and without history of atherosclerotic CV disease (CVD). Methods: This randomized, double-blind, placebo-controlled trial included patients with T2D and urine albumin-to-creatinine ratio 30-5000 mg/g and an estimated glomerular filtration rate (eGFR) ≥25-<75 mL/min/1.73 m 2 , treated with optimized renin-angiotensin system blockade. Patients with a history of heart failure with reduced ejection fraction were excluded. Patients were randomized 1:1 to receive finerenone or placebo. The composite CV outcome included time to CV death, myocardial infarction, stroke, or hospitalization for heart failure. Prespecified CV analyses included analyses of the components of this composite and outcomes according to CVD history at baseline. Results: Between September 2015 and June 2018, 13,911 patients were screened and 5674 were randomized; 45.9% of patients had CVD at baseline. Over a median follow-up of 2.6 years (interquartile range, 2.0-3.4 years), finerenone reduced the risk of the composite CV outcome compared with placebo (hazard ratio [HR], 0.86; 95% confidence interval [CI], 0.75-0.99; P=0.034), with no significant interaction between patients with and without CVD (HR, 0.85; 95% CI, 0.71-1.01 in patients with a history of CVD; HR, 0.86; 95% CI, 0.68-1.08 in patients without a history of CVD; P-value for interaction, 0.85). The incidence of treatment-emergent adverse events was similar between treatment arms, with a low incidence of hyperkalemia-related permanent treatment discontinuation (2.3% with finerenone vs 0.8% with placebo in patients with CVD and 2.2% with finerenone vs 1.0% with placebo in patients without CVD). Conclusions: Among patients with CKD and T2D, finerenone reduced incidence of the composite CV outcome, with no evidence of differences in treatment effect based on pre-existing CVD status. Clinical Trial Registration: URL: https://clinicaltrials.gov Unique Identifier: NCT02540993 (Funded by Bayer AG)

Management of Kidney Failure in Patients with Diabetes Mellitus: What Are the Best Options?

“…Another drug of interest is finerenone (non-steroidal antagonist of the mineralocorticoid receptor). In the FIDELIO-DKD study, it shows a decrease in the incidence of cardiovascular events (HR, 0.86; 95% CI, 0.75 to 0.99; p = 0.034), as well as a decreased in kidney events (HR, 0.82; 95% CI, 0.73 to 0.93; p = 0.001) in patients with GFR 25-75 mL/min/1.73 m 2 [53,54].…”

Mineralocorticoid Receptor Antagonists in Diabetic Kidney Disease

“…Hyperkalemia was more common in the finerenone group, but discontinuation of the trial due to it was uncommon (2.3%). An additional subgroup analysis of these data showed that finerenone lowered the incidence of the composite cardiovascular outcome independent of preexisting cardiovascular diseases [133]. Another big phase 3 clinical trial was FIGARO-DKD (FInerenone in reducinG cArdiovascular moRtality and mOrbidity in Diabetic Kidney Disease), that investigated the role of finerenone in reducing major cardiovascular events, with slowing DKD progression as a prespecified secondary endpoint [15,134].…”

Posttranslational Modifications of the Mineralocorticoid Receptor and Cardiovascular Aging

“…However, when looking at subgroups, some benefits of MR antagonists were found depending on the geographical origin of the patients, sex and age (Pitt et al, 2014;Pfeffer et al, 2015;Merrill et al, 2019). Recently published results show that new MR antagonists reduce the risk of chronic kidney disease progression and cardiovascular events in patients with chronic kidney disease and type 2 diabetes regardless of pre-existing cardiovascular problems (Bakris et al, 2020;Filippatos et al, 2021). Therefore, results from clinical trials suggest that an overactive RAAS is accountable for some of the cardiovascular changes occurring in cardiovascular diseases and in an attenuated form also during healthy aging.…”