Finerenone, a non-steroidal MRA

Finerenone, a non-steroidal MRA

Finerenone is a nonsteroidal, selective mineralocorticoid receptor antagonist. Finerenone is thought to have lower risk of hyperkalemia and renal issues compared to other MRAs. It has been shown to reduce albuminuria in patients with chronic kidney disease and type 2 diabetes mellitus. FInerenone in reducing kiDnEy faiLure and dIsease prOgression in Diabetic Kidney Disease (FIDELIO-DKD) study evaluated the renal and cardiovascular outcomes in patients with CKD and type 2 diabetes mellitus. 5734 patients with CKD and type 2 diabetes were randomized to finerenone or placebo. All patients were on renin-angiotensin system blockade before randomization to the maximum tolerated safe dose. It was shown that treatment with finerenone resulted in lower risk of progression of CKD and cardiovascular events than placebo [1].

A subsequent report gave the individual cardiovascular outcomes in patients with without history of atherosclerotic cardiovascular disease. The composite cardiovascular outcome assessed included time to cardiovascular death, myocardial infarction, stroke, or hospitalization for heart failure. Over a median follow-up of 2.6 years, finerenone reduced the risk of the composite cardiovascular outcome compared with placebo. There was no significant difference between patients with and without history of cardiovascular disease. There was no significant difference in the hyperkalemia related permanent discontinuation between these two groups. The figures for finerenone were 2.3 and 2.2% compared to 0.8% and 1.0% for placebo, showing a low incidence [2].

Still another analysis of FIDELIO-DKD reported that  finerenone reduced the risk of new-onset atrial fibrillation or flutter [3]. It may be noted that patients with CKD and type 2 diabetes mellitus are at risk of atrial fibrillation or flutter due cardiac remodeling. Finerenone had been shown to inhibit cardiac remodeling in preclinical studies.

FInerenone in reducinG cArdiovascular moRtality and mOrbidity in Diabetic Kidney Disease (FIGARO-DKD) study also reported cardiovascular outcomes with finerenone in patients with CKD and type 2 diabetes mellitus. These patients were also on recommended maximum tolerated doses of renin-angiotensin system blockers. The double blind trial had randomized 7437 patients. Primary outcome was a composite of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke or hospitalization for heart failure, assessed in a time-to-event analysis. During a median follow up of 3.4 years, primary outcome event occurred in 458 patients in finerenone group and 519 patients in the placebo group. The benefit was driven primarily by a lower incidence of hospitalization for heart failure. Overall frequency of adverse events were not substantially different between the groups. Hyperkalemia-related discontinuation was 1.2% with finerenone and 0.4% with placebo [4].

Another analysis from FIGARO-DKD reported that finerenone reduces the risk of incident heart failure in patients with CKD and type 2 diabetes mellitus. New onset heart failure was 1.9% in the finerenone group while it was 2.8% in the placebo group. There was 29% lower risk of first hospitalization for heart failure and 30% lower risk of total hospitalization for heart failure. This improvement was not modified by a history of heart failure [5].

FINEARTS – HF (Finerenone in Heart Failure Patients) is evaluating the effect of finerenone in heart failure with left ventricular ejection fraction of 40% or more. The study (ClinicalTrials.gov Identifier: NCT04435626) started in September 2020 is planning to enroll 6000 patients  and is expected to be completed in September 2024.

References

1. Bakris GL, Agarwal R, Anker SD, Pitt B, Ruilope LM, Rossing P, Kolkhof P, Nowack C, Schloemer P, Joseph A, Filippatos G; FIDELIO-DKD Investigators. Effect of Finerenone on Chronic Kidney Disease Outcomes in Type 2 Diabetes. N Engl J Med. 2020 Dec 3;383(23):2219-2229. doi: 10.1056/NEJMoa2025845. Epub 2020 Oct 23. PMID: 33264825.
2. Filippatos G, Anker SD, Agarwal R, Pitt B, Ruilope LM, Rossing P, Kolkhof P, Schloemer P, Tornus I, Joseph A, Bakris GL; FIDELIO-DKD Investigators. Finerenone and Cardiovascular Outcomes in Patients With Chronic Kidney Disease and Type 2 Diabetes. Circulation. 2021 Feb 9;143(6):540-552. doi: 10.1161/CIRCULATIONAHA.120.051898. Epub 2020 Nov 16. PMID: 33198491; PMCID: PMC7864612.
3. Filippatos G, Bakris GL, Pitt B, Agarwal R, Rossing P, Ruilope LM, Butler J, Lam CSP, Kolkhof P, Roberts L, Tasto C, Joseph A, Anker SD; FIDELIO-DKD Investigators. Finerenone Reduces New-Onset Atrial Fibrillation in Patients With Chronic Kidney Disease and Type 2 Diabetes. J Am Coll Cardiol. 2021 Jul 13;78(2):142-152. doi: 10.1016/j.jacc.2021.04.079. Epub 2021 May 17. PMID: 34015478.
4. Pitt B, Filippatos G, Agarwal R, Anker SD, Bakris GL, Rossing P, Joseph A, Kolkhof P, Nowack C, Schloemer P, Ruilope LM; FIGARO-DKD Investigators. Cardiovascular Events with Finerenone in Kidney Disease and Type 2 Diabetes. N Engl J Med. 2021 Dec 9;385(24):2252-2263. doi: 10.1056/NEJMoa2110956. Epub 2021 Aug 28. PMID: 34449181.
5. Filippatos G, Anker SD, Agarwal R, Ruilope LM, Rossing P, Bakris GL, Tasto C, Joseph A, Kolkhof P, Lage A, Pitt B; FIGARO-DKD Investigators. Finerenone Reduces Risk of Incident Heart Failure in Patients With Chronic Kidney Disease and Type 2 Diabetes: Analyses From the FIGARO-DKD Trial. Circulation. 2022 Feb 8;145(6):437-447. doi: 10.1161/CIRCULATIONAHA.121.057983. Epub 2021 Nov 13. PMID: 34775784; PMCID: PMC8812430.
6. Study to Evaluate the Efficacy and Safety of Finerenone on Morbidity  & Mortality  in Participants With Heart Failure and Left Ventricular Ejection Fraction Greater or Equal to 40% (FINEARTS-HF). (ClinicalTrials.gov Identifier: NCT04435626. Accessed on 24 September 2022.