Multiple benefits of Finerenone- Reduces renal-risk besides cardiac protection in diabetics
Finerenone, a nonsteroidal, selective mineralocorticoid receptor antagonist, has been shown to reduce albuminuria in short-term trials involving patients with chronic kidney disease (CKD) and type 2 diabetes. Now, in a study published in NEJM, FIDELIO-DKD trial investigators have shown that finerenone slows CKD progression and reduces cardiovascular morbidity and mortality among patients with advanced CKD and type 2 diabetes.
Evidence supports a pathophysiological role for overactivation of the mineralocorticoid receptors in cardiorenal diseases, including CKD and diabetes, through inflammation and fibrosis that leads to progressive kidney and cardiovascular dysfunction. Strategies to decrease aldosterone activation for improving cardiovascular outcomes have attracted interest in the past 3 decades and steroidal drugs like spironolactone and eplerenone have been used but they have a significant side-effect profile (gynecomastia, erectile dysfunction, etc) and renal safety concerns due to the risk of hyperkalemia. In contrast, the non-steroidal dihydropyridine finerenone is a selective inhibitor and has better tolerability and safety profile.
Bakris et al. report have reported in NEJM, the results of the phase 3 Finerenone in Reducing Kidney Failure and Disease Progression in Diabetic Kidney Disease (FIDELIO-DKD) trial. In this double-blind trial, they randomly assigned 5734 patients with CKD and type 2 diabetes in a 1:1 ratio to receive finerenone or placebo. All the patients were pre-treated with a maximum tolerable dose of renin-angiotensin system blocking drugs.
1. 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.
2. 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.
During a median follow-up of 2.6 years, a primary outcome event occurred in 17.8% of patients in the finerenone group and 21.1% in the placebo group (hazard ratio, 0.82; P = 0.001). A key secondary outcome event occurred in 13.0% and 14.8% in the respective groups (hazard ratio of 0.86, 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), but this was markedly lower than in trials of dual RAS blockade (4.8% with combination therapy with a direct renin inhibitor and an ACE inhibitor or ARB and 9.2% with dual ACE inhibitor and ARB therapy)
To summarise, they found a benefit of finerenone as compared with placebo with respect to CKD progression among patients with relatively advanced CKD and diabetes and thus for persons at high risk for kidney-related (and heart-related) events. A cardiovascular benefit was evident early (as soon as a month) and continued in the long-term; the kidney-related benefit was seen after 1 year.
Further insight into the cardiorenal efficacy and safety of finerenone in patients with type 2 diabetes and less advanced CKD will be provided by the ongoing Finerenone in Reducing Cardiovascular Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial.
The complete article is available as Bakris GL, Agarwal R, Anker SD, et al. Effect of finerenone on chronic kidney disease outcomes in type 2 diabetes. N Engl J Med. DOI: 10.1056/NEJMoa2025845.
Available from: https://www.nejm.org/doi/full/10.1056/NEJMoa2025845
