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)
Angiotensin Receptor-Neprilysin Inhibition Based on History of Heart Failure and Use of Renin-Angiotensin System Antagonists