Finerenone improves cardiorenal outcomes among patients of diabetes with CKD: The FIDELITY Trial

U.S.A.: A trial that was recently published in the Journal of the American College of Cardiology reported that finerenone, a selective, nonsteroidal mineralocorticoid receptor antagonist, improved cardiorenal outcomes in patients who had chronic kidney disease (CKD) and Type 2 Diabetes.

"Despite current treatments, patients with chronic kidney disease (CKD) and type 2 diabetes have significant rates of residual cardiorenal morbidity and mortality, and the likelihood that kidney failure will eventually set in as well as cardiovascular events rises with the severity and stage of CKD," the authors wrote.

In preclinical kidney and cardiovascular disease models, finerenone has shown anti-inflammatory and anti-fibrotic properties. It is a new, selective, nonsteroidal MR antagonist (MRA) that inhibits MR-mediated salt reabsorption and MR overactivation. Yet, finerenone's effectiveness and safety have not been well assessed in type 2 diabetic patients with CKD across the board.

"Screening for albuminuria to identify at-risk patients among patients with type 2 diabetes facilitates reduction of both cardiovascular and kidney disease burden," added the researchers.

In this study, the efficacy of finerenone on HF outcomes by eGFR and/or UACR categories were assessed.

13,026 participants with T2D and CKD (UACR 30-5,000 mg/g and eGFR ≥ 25 mL/min/1.73 m2) were randomly assigned to finerenone or placebo in this FIDELITY trial. First heart failure hospitalization (HHF), cardiovascular death or first HHF, recurring HHF, and cardiovascular death or recurrent HHF were time-to-event outcomes that were divided into subgroups based on baseline eGFR (<60 and ≥60 mL/min/1.73 m2) and/or UACR (<300 and ≥300 mg/g).

Key results of the trial:

• As compared to placebo, finerenone substantially decreased the incidence of first HHF (HR: 0.78 [95% CI: 0.66-0.92]; P = 0.003), cardiovascular death or first HHF (HR: 0.83 [95% CI: 0.74-0.93]; P = 0.002), recurrent HHF (HR: 0.79 [95% CI: 0.64-0.96]; P = 0.021), and recurrent HHF (HR: 0.82 [95% CI: 0.72-0.95]; P = 0.006).
• In all baseline eGFR and UACR categories, the risk of outcomes rose; the patients with the lowest occurrences had eGFRs of 60 mL/min/1.73 m2 and UACRs of 300 mg/g.
• No matter the initial eGFR or UACR classifications (all P interaction values >0.10), finerenone enhanced HF outcomes.

The authors concluded that, compared to placebo, finerenone decreased the probability of clinically significant renal and cardiovascular outcomes in patients with type 2 diabetes across the full range of CKD.

REFERENCE

Filippatos G, Anker S, Pitt B, et al. Finerenone and Heart Failure Outcomes by Kidney Function/Albuminuria in Chronic Kidney Disease and Diabetes. J Am Coll Cardiol HF. null2022, 0 (0) . https://doi.org/10.1016/j.jchf.2022.07.013