Finerenone lowers CV events in diabetic CKD patients

In the FIDELIO-DKD trial, finerenone treatment lowered the risk of chronic kidney disease (CKD) progression and of cardiovascular (CV) events in patients with type 2 diabetes and advanced CKD [1]. There were no differences in treatment effect depending on pre-existing CVD status. The results demonstrated benefits of finerenone for both primary and secondary CV prevention.

Prof. Gerasimos Filippatos (National and Kapodistrian University of Athens, Greece) shared the results of the phase 3 FIDELIO-DKD trial (NCT02540993), which was designed to evaluate the efficacy of finerenone in slowing CKD progression and reducing CV events in patients diagnosed with advanced CKD and type 2 diabetes; these results were simultaneously published in the New England Journal of Medicine [1,2]. Finerenone is a non-steroidal, selective mineralocorticoid receptor antagonist which reduces the urinary albumin-to-creatinine ratio in patients with.

FIDELIO-DKD randomised 5,734 participants across 48 countries to receive either a once-daily dose of 10 mg or 20 mg oral finerenone or placebo. During a run-in period of 4–16 weeks, CV and diabetes therapy was optimised; RAS inhibitors were titrated to a maximum dose. Adults with type 2 diabetes and CKD who were treated with a RAS inhibitor at the maximum dose on the manufacturer’s label were eligible. Median follow-up was 2.6 years. The primary endpoint was a kidney composite endpoint of time to kidney failure, sustained ≥40% decrease of estimated glomerular filtration rate (eGFR) decrease from baseline, or death from renal causes.

The primary endpoint occurred in 504 (17.8%) and 600 (21.1%) participants in the finerenone and control group, respectively (HR 0.82; 95% CI 0.73–0.93; P=0.0014). The number of participants requiring finerenone treatment to prevent one primary outcome was 29. The key secondary endpoint was a CV composite endpoint of time to CV death, non-fatal MI, non-fatal stroke, or hospitalisation for HF. This endpoint was reached by 367 (13.0%) versus 420 (14.8%) participants in the finerenone and placebo groups, respectively (HR 0.86; 95% CI 0.75–0.99; P=0.03). In the finerenone group, there was a relative risk reduction of 20% for non-fatal MI (HR 0.80; 95% CI 0.58–1.09), while the incidence of non-fatal stroke was similar (HR 1.03; 95% CI 0.76–1.38). Prof. Filippatos added that the CV benefit on finerenone was consistent across subgroups with CV disease (including atherosclerotic CV disease and HF) and without CV disease.

The incidence of treatment-emergent adverse events (AE) and serious AEs was similar between both groups. The rate of serious AEs was 31.9% in the finerenone group and 34.3% in the placebo group. Specifically, hyperkalaemia-related AEs were twice as frequent in the finerenone group (18.3% versus 9.0%); these events were manageable. There was a modest effect on blood pressure, with a mean maximum decrease of 3.2 mmHg. The safety profile was similar for patients with and without CV disease.

In conclusion, FIDELIO-DKD demonstrated that finerenone treatment lowered the risk of CKD progression and CV events in participants diagnosed with type 2 diabetes and advanced CKD.

1. 
   
   1. Filippatos G, et al. Finerenone and Cardiovascular Outcomes in Patients With Chronic Kidney Disease and Type 2 Diabetes. LBS.07, AHA Scientific Sessions 2020, 13–17 Nov.
   2. Bakris GL, et al. New Engl J Med 2020;383:2219-2229.

 



Posted on 18 February 202117 May 2024