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 - © Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
PY - 2024/3/19
Y1 - 2024/3/19
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); Pinteraction=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); Pinteraction=0.99). Effects on HHF reduction were not modified by age (Pinteraction=0.70) but appeared more pronounced in males (Pinteraction=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 (Pinteraction=0.51). In sex subgroups, finerenone consistently reduced kidney events (Pinteraction=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.TRIAL REGISTRATION NUMBERS: NCT02540993, NCT02545049.
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); Pinteraction=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); Pinteraction=0.99). Effects on HHF reduction were not modified by age (Pinteraction=0.70) but appeared more pronounced in males (Pinteraction=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 (Pinteraction=0.51). In sex subgroups, finerenone consistently reduced kidney events (Pinteraction=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.TRIAL REGISTRATION NUMBERS: NCT02540993, NCT02545049.
KW - Adult
KW - Humans
KW - Male
KW - Female
KW - Middle Aged
KW - Diabetes Mellitus, Type 2/complications
KW - Kidney
KW - Naphthyridines/therapeutic use
KW - Double-Blind Method
KW - Renal Insufficiency, Chronic/drug therapy
KW - Heart Failure/complications
KW - cardiovascular disease
KW - risk factors
KW - diabetes & endocrinology
KW - diabetic nephropathy & vascular disease
UR - http://www.scopus.com/inward/record.url?scp=85188318691&partnerID=8YFLogxK
U2 - 10.1136/bmjopen-2023-076444
DO - 10.1136/bmjopen-2023-076444
M3 - Journal article
C2 - 38508632
SN - 2044-6055
VL - 14
SP - e076444
JO - BMJ Open
JF - BMJ Open
IS - 3
M1 - e076444
ER -