Finerenone cardiovascular and kidney outcomes by age and sex: FIDELITY post hoc analysis of two phase 3, multicentre, double-blind trials.

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=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=0.99). Effects on HHF reduction were not modified by age (P=0.70) but appeared more pronounced in males (P=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=0.51). In sex subgroups, finerenone consistently reduced kidney events (P=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.