open access publication

Article, 2024

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

BMJ Open, ISSN 2044-6055, Volume 14, 3, Page e076444, 10.1136/bmjopen-2023-076444

Contributors

Bansal, Shweta 0000-0002-3306-2799 (Corresponding author) [1] Canziani, Maria Eugênia Fernandes 0000-0002-9645-5303 [2] Birne, Rita 0000-0001-5172-025X [3] [4] Anker, Stefan D [5] Bakris, George Louis 0000-0003-1183-1267 [6] Filippatos, Gerasimos S 0000-0002-5640-0332 [7] Rossing, Peter R 0000-0002-1531-4294 [8] [9] Ruilope, Luis M [10] [11] [12] Farjat, Alfredo E [13] Kolkhof, Peter 0000-0003-3425-7528 [14] Lage, Andrea Z [15] Brinker, Meike Daniela [14] Pitt, Bertram A 0000-0001-5880-275X [16]

Affiliations

  1. [1] The University of Texas Health Science Center at San Antonio
    2. [NORA names: United States; America, North; OECD];
  2. [2] Federal University of São Paulo
    3. [NORA names: Brazil; America, South];
  3. [3] Centro Hospitalar de Lisboa Ocidental
    4. [NORA names: Portugal; Europe, EU; OECD];
  4. [4] University of Lisbon
    5. [NORA names: Portugal; Europe, EU; OECD];
  5. [5] Charité - University Medicine Berlin
    6. [NORA names: Germany; Europe, EU; OECD];

Abstract

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.

Keywords

FIDELIO-DKD, FIGARO-DKD, HHF, Secondary outcome measures, adults, age, age groups, age subgroups, albuminuria, analysis, antagonist, cardiovascular benefits, categories, chronic kidney disease, composite outcome, decline, discontinuation, discontinuation rates, disease, double-blind trial, eGFR, eGFR decline, effect, efficacy, events, fidelity, finerenone, follow-up, group, gynaecomastia, heterogeneity, hoc analysis, hyperkalaemia, inhibitors, kidney, kidney composite outcome, kidney disease, kidney events, kidney outcomes, lt;65, male, mean age, measurements, median follow-up, mineralocorticoid receptor antagonists, multicentre, non-steroidal mineralocorticoid receptor antagonist, outcomes, phase, phase 3, placebo, post hoc analysis, primary, profile, rate, receptor antagonist, reduction, renin-angiotensin system inhibitors, safety, safety of finerenone, safety profile, secondaries, sex, sex categories, sex subgroups, study, subgroups, system inhibitors, treatment, treatment effects, treatment groups, trials, type, type 2 diabetes, years

Funders

  • Bayer (United States)
  • Johnson Space Center

Data Provider: Digital Science

LINKS
-

Matching Records in NORA

SUBJECTS
+

METRICS
+