TY - JOUR

T1 - Finerenone cardiovascular and kidney outcomes by age and sex

T2 - FIDELITY post hoc analysis of two phase 3, multicentre, double-blind trials

AU - Bansal, Shweta

AU - Canziani, Maria E.F.

AU - Birne, Rita

AU - Anker, Stefan D

AU - Bakris, George L

AU - Filippatos, Gerasimos

AU - Rossing, Peter

AU - Ruilope, Luis M

AU - Farjat, Alfredo E.

AU - Kolkhof, Peter

AU - Lage, Andrea

AU - Brinker, Meike

AU - Pitt, Bertram

N1 - Publisher Copyright: © 2024 BMJ Publishing Group. All rights reserved.

PY - 2024

Y1 - 2024

N2 - Objectives This study aimed to evaluate the efficacy and safety of finerenone, a selective, non-steroidal mineralocorticoid receptor antagonist, on cardiovascular and kidney outcomes by age and/or sex. Design FIDELITY post hoc analysis; median follow-up of 3 years. Setting FIDELITY: a prespecified analysis of the FIDELIO-DKD and FIGARO-DKD trials. Participants Adults with type 2 diabetes and chronic kidney disease receiving optimised renin-angiotensin system inhibitors (N=13 026). Interventions Randomised 1:1; finerenone or placebo. Primary and secondary outcome measures Cardiovascular (cardiovascular death, non-fatal myocardial infarction, non-fatal stroke or hospitalisation for heart failure (HHF)) and kidney (kidney failure, sustained ≥57% estimated glomerular filtration rate (eGFR) decline or renal death) composite outcomes. Results Mean age was 64.8 years; 45.2%, 40.1% and 14.7% were aged <65, 65-74 and ≥75 years, respectively; 69.8% were male. Cardiovascular benefits of finerenone versus placebo were consistent across age (HR 0.94 (95% CI 0.81 to 1.10) (<65 years), HR 0.84 (95% CI 0.73 to 0.98) (65-74 years), HR 0.80 (95% CI 0.65 to 0.99) (≥75 years); P interaction =0.42) and sex categories (HR 0.86 (95% CI 0.77 to 0.96) (male), HR 0.89 (95% CI 0.35 to 2.27) (premenopausal female), HR 0.87 (95% CI 0.73 to 1.05) (postmenopausal female); P interaction =0.99). Effects on HHF reduction were not modified by age (P interaction =0.70) but appeared more pronounced in males (P interaction =0.02). Kidney events were reduced with finerenone versus placebo in age groups <65 and 65-74 but not ≥75; no heterogeneity in treatment effect was observed (P interaction =0.51). In sex subgroups, finerenone consistently reduced kidney events (P interaction =0.85). Finerenone reduced albuminuria and eGFR decline regardless of age and sex. Hyperkalaemia increased with finerenone, but discontinuation rates were <3% across subgroups. Gynaecomastia in males was uncommon across age subgroups and identical between treatment groups. Conclusions Finerenone improved cardiovascular and kidney composite outcomes with no significant heterogeneity between age and sex subgroups; however, the effect on HHF appeared more pronounced in males. Finerenone demonstrated a similar safety profile across age and sex subgroups.

AB - Objectives This study aimed to evaluate the efficacy and safety of finerenone, a selective, non-steroidal mineralocorticoid receptor antagonist, on cardiovascular and kidney outcomes by age and/or sex. Design FIDELITY post hoc analysis; median follow-up of 3 years. Setting FIDELITY: a prespecified analysis of the FIDELIO-DKD and FIGARO-DKD trials. Participants Adults with type 2 diabetes and chronic kidney disease receiving optimised renin-angiotensin system inhibitors (N=13 026). Interventions Randomised 1:1; finerenone or placebo. Primary and secondary outcome measures Cardiovascular (cardiovascular death, non-fatal myocardial infarction, non-fatal stroke or hospitalisation for heart failure (HHF)) and kidney (kidney failure, sustained ≥57% estimated glomerular filtration rate (eGFR) decline or renal death) composite outcomes. Results Mean age was 64.8 years; 45.2%, 40.1% and 14.7% were aged <65, 65-74 and ≥75 years, respectively; 69.8% were male. Cardiovascular benefits of finerenone versus placebo were consistent across age (HR 0.94 (95% CI 0.81 to 1.10) (<65 years), HR 0.84 (95% CI 0.73 to 0.98) (65-74 years), HR 0.80 (95% CI 0.65 to 0.99) (≥75 years); P interaction =0.42) and sex categories (HR 0.86 (95% CI 0.77 to 0.96) (male), HR 0.89 (95% CI 0.35 to 2.27) (premenopausal female), HR 0.87 (95% CI 0.73 to 1.05) (postmenopausal female); P interaction =0.99). Effects on HHF reduction were not modified by age (P interaction =0.70) but appeared more pronounced in males (P interaction =0.02). Kidney events were reduced with finerenone versus placebo in age groups <65 and 65-74 but not ≥75; no heterogeneity in treatment effect was observed (P interaction =0.51). In sex subgroups, finerenone consistently reduced kidney events (P interaction =0.85). Finerenone reduced albuminuria and eGFR decline regardless of age and sex. Hyperkalaemia increased with finerenone, but discontinuation rates were <3% across subgroups. Gynaecomastia in males was uncommon across age subgroups and identical between treatment groups. Conclusions Finerenone improved cardiovascular and kidney composite outcomes with no significant heterogeneity between age and sex subgroups; however, the effect on HHF appeared more pronounced in males. Finerenone demonstrated a similar safety profile across age and sex subgroups.

KW - cardiovascular disease

KW - diabetes & endocrinology

KW - diabetic nephropathy & vascular disease

KW - risk factors

U2 - 10.1136/bmjopen-2023-076444

DO - 10.1136/bmjopen-2023-076444

M3 - Journal article

C2 - 38508632

AN - SCOPUS:85188318691

VL - 14

JO - BMJ Open

JF - BMJ Open

SN - 2044-6055

IS - 3

M1 - e076444

ER -