Beneficial effects of non-steroidal MRA on HF-related outcomes in CKD and T2DM
Finerenone and heart failure outcomes by kidney function/albuminuria in chronic kidney disease and diabetes
Literature - Filippatos G, Anker SD, Pitt B, et al. - JACC Heart Fail. 2022 Nov;10(11):860-870. doi: 10.1016/j.jchf.2022.07.013.Introduction and methods
Background
In patients with T2DM, the risk of CV death and HF increases with decreasing kidney function (eGFR) and increasing albuminuria (urine albumin-to-creatinine ratio, UACR) [1,2]. Finerenone is a selective, non-steroidal MRA approved by the FDA and EMA for the treatment of CKD in adult patients with T2DM [3,4]. Previously, a pooled analysis of individual patient data from the FIDELIO-DKD and FIGARO-DKD trials (FIDELITY study) showed that treatment with finerenone improves cardiorenal outcomes in these patients [5-7]. However, it is unclear whether this also applies to HF-related outcomes.
Aim of the study
The aim of this analysis of the FIDELITY study was to examine the effects of finerenone on HF-related outcomes in adult patients with CKD and T2DM, stratified by baseline eGFR and/or UACR.
Methods
The researchers performed a pooled analysis of individual patient data from the FIDELIO-DKD and FIGARO-DKD trials (FIDELITY study). In these placebo-controlled, double-blind, randomized phase 3 studies, a total of 13,026 adults with CKD (defined as UACR 30-<300 mg/g with eGFR ≥25 to<60 mL/min per 1.73 m2 and retinopathy in FIDELIO-DKD or eGFR 25 to ≤90 mL/min per 1.73 m2 in FIGARO-DKD; or UACR of 300-5000 mg/g and eGFR ≥25 to <75 mL/min/1.73 m2 in FIDELIO-DKD or ≥60 mL/min/1.73 m2 in FIGARO-DKD) and T2DM were randomized to treatment with once-daily 10 or 20 mg finerenone or placebo. Additional inclusion criteria were treatment with an ACEi or ARB for ≥4 weeks at a maximum tolerated labeled dose and a serum potassium concentration 4.8 mmol/L. Patients with HFrEF and NYHA class II-IV symptoms, patients with a history of stroke, TIA or ACS, and patients hospitalized for worsening HF within the past 30 days were excluded from participation.
Outcomes
'Time-to-event' outcomes were: (a) first hospitalization for HF; (b) CV death or first hospitalization for HF; (c) recurrent hospitalization for HF; and (d) CV death or recurrent hospitalization for HF. These outcomes were analyzed in the overall study population and in subgroups based on baseline eGFR (<60 and ≥60 mL/min per 1.73 m2) and/or UACR (<300 and ≥300 mg/g).
Main results
Overall study population
- Compared with placebo, finerenone reduced the risk of first hospitalization for HF (HR: 0.78; 95%CI: 0.66-0.92; P=0.003), CV death or first hospitalization for HF (HR: 0.83; 95%CI: 0.74-0.93; P=0.002), recurrent hospitalization for HF (HR: 0.79; 95%CI: 0.64-0.96; P=0.021), and CV death or recurrent hospitalization for HF (HR: 0.82; 95%CI: 0.72-0.95; P=0.006).
Subgroups
- There was no difference in the reductions of HF-related outcomes with finerenone vs. placebo in patients with a baseline eGFR ≥60 mL/min per 1.73 m2 compared with patients with baseline <60 mL/min per 1.73 m2 (Pinteractions≥0.15).
- Consistently, reductions in risk of HF-related outcomes with finerenone vs. placebo in patients with UACR <300 mg/g compared with patients with UACR ≥300 mg/g were not significantly different (Pinteractions>0.20).
- The largest relative risk reduction was seen in the combined subgroup of patients with an eGFR ≥60 mL/min per 1.73 m2 and a UACR <300 mg/g (43-70% reduction across all HF-related outcomes).
Conclusion
This analysis of the FIDELITY study (FIDELITY-HF) shows that in adult patients with CKD and T2DM, treatment with finerenone improved HF-related outcomes, compared with placebo. The beneficial effects of finerenone were independent of baseline eGFR and/or UACR.
References
1. Fox CS, Matsushita K, Woodward M, et al. Associations of kidney disease measures with mortality and end-stage renal disease in individuals with and without diabetes: a meta-analysis. Lancet. 2012;380(9854):1662-73.
2. Matsushita K, Coresh J, Sang Y, et al. Estimated glomerular filtration rate and albuminuria for prediction of cardiovascular outcomes: a collaborative meta-analysis of individual participant data. Lancet Diabetes Endocrinol. 2015;3(7): 514-25.
3. Kerendia: EPAR – Public Assessment Report. EMA/78746/2022. Amsterdam: European Medicines Agency; 2021.
4. FDA approves drug to reduce risk of serious kidney and heart complications in adults with chronic kidney disease associated with type 2 diabetes | FDA
5. Bakris GL, Agarwal R, Anker SD, et al. Effect of finerenone on chronic kidney disease outcomes in type 2 diabetes. N Engl J Med. 2020;383(23): 2219-29.
6. Filippatos G, Anker SD, Agarwal R, et al. 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;145(6):437-47.
7. Agarwal R, Filippatos G, Pitt B, et al. Cardiovascular and kidney outcomes with finerenone in patients with type 2 diabetes and chronic kidney disease: the FIDELITY pooled analysis. Eur Heart J. 2022;43(6):474-84.
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