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Gerasimos Filippatos

Publications and source records attributed to Gerasimos Filippatos.

4 recordsLinked to original sources
PubMed2026

Proteomic patterns according to ejection fraction: an EMPEROR-programme analysis.

AIMS: Left ventricular ejection fraction (LVEF) has been incorporated as an inclusion criterion in HF trials. Patient's characteristics, event risk, and treatment response vary according to LVEF. A better understanding of the biological processes across LVEF is warranted. To study proteomic biomarker expression across LVEF using data from the EMPEROR-Programme. METHODS: Two thousand two hundred and fifty-four patients who had proteomic measurements available using 1134 proteins overlapping between the Explore 1536 and 3072 Olink® platforms were included. Main analyses were performed within the EMPEROR-Preserved dataset due to differences in entry criteria between EMPEROR-Preserved and EMPEROR-Reduced with higher entry N-terminal pro B-type natriuretic peptide (NT-proBNP) levels that varied by LVEF cut-offs in the latter. Protein concentrations were compared using ordinal logistic regression across LVEF categories: 41%-49%, 50%-59%, and ≥60%. The resulting β-coefficient indicates the change in the log-odds for the outcome of being in a lower LVEF category for every NPX unit in log2 scale. Analyses were adjusted for covariates and a false-discovery-rate (FDR) correction was applied. RESULTS: A total of 297 proteins exhibited a trend of expression across LVEF categories in EMPEROR-Preserved after adjustment for potential confounders and correction for test multiplicity. Of these, the top 10 proteins were: NT-pro BNP (β = 0.18, 95% CI 0.09-0.27), Wnt inhibitory factor-1 (β = 0.40, 95% CI 0.19-0.61), sialomucin core protein 24 (β = 0.48, 95% CI 0.22-0.74), phospholipid transfer protein (β = 0.38, 95% CI 0.17-0.59), natriuretic peptides B (β = 0.13, 95% CI 0.06-0.20), intercellular adhesion molecule 5 (β = 0.31, 95% CI 0.14-0.49), neural cell adhesion molecule 2 (β = 0.45, 95% CI 0.19-0.70), neural cell adhesion molecule L1-like protein (β = 0.45, 95% CI 0.19-0.71), interactor protein for cytohesin exchange factors 1 (β = 0.12, 95% CI 0.05-0.19), and 3-ketoacyl-CoA thiolase, peroxisomal (β = 0.17, 95% CI 0.07-0.26). The correlation between these proteins and LVEF was generally weak (Rho ≤0.2). CONCLUSIONS: Within EMPEROR-Preserved, the top differentially expressed circulating proteins suggest that pathways related to natriuretic peptides, cell-adhesion, and clonal haematopoiesis are overexpressed at mildly-reduced ejection fraction, but none of the proteins passed the 5%FDR cut-off, and the correlation between circulating proteins and LVEF was weak. These findings suggest that circulating proteins may not be a good discriminant of ejection fraction.

Humans↗
PubMed2026

Efficacy and Safety of the Kidney Function-Based Finerenone Dosing Strategy Used in FINEARTS-HF.

BACKGROUND: Given that mineralocorticoid receptor antagonists have the potential to impair renal function and induce hyperkalemia, close monitoring of estimated glomerular filtration rate (eGFR) and serum potassium levels is essential to ensure the safe administration of this therapy. OBJECTIVES: In this prespecified analysis, the authors evaluated the efficacy and safety of the kidney function-based finerenone dosing strategy used in the FINEARTS-HF trial. METHODS: In FINEARTS-HF, patients with an eGFR of 25 to 60&#x2009;mL/min/1.73&#x2009;m2 at baseline were stratified at randomization to the low-dose group and started on 10&#x2009;mg of finerenone once daily (titrated to a maximum 20&#x2009;mg/d) or matching placebo, whereas those with an eGFR >60&#x2009;mL/min/1.73&#x2009;m2 at baseline were stratified to the high-dose group and started on 20&#x2009;mg of finerenone once daily (titrated to a maximum 40&#x2009;mg/d) or matching placebo. The primary outcome was the composite of total (first and recurrent) heart failure events and cardiovascular death. RESULTS: Among 5,986 (99.8%) analyzable patients, 3,159 were assigned to the higher eGFR/high-dose stratum and 2,827 to the lower eGFR/low-dose stratum group. The mean &#xb1; SD achieved dose was 32.3&#x2009;&#xb1;&#x2009;9.1&#x2009;mg (finerenone) and 34.4&#x2009;&#xb1;&#x2009;7.8&#x2009;mg (placebo) in the higher eGFR/high-dose stratum, and 15.6&#x2009;&#xb1;&#x2009;4.3&#x2009;mg (finerenone) and 16.7&#x2009;&#xb1;&#x2009;4.0 mg (placebo) in the lower eGFR/low-dose stratum. The effect of finerenone on the primary outcome was consistent across the 2 dosing strata (higher eGFR/high-dose stratum: rate ratio: 0.77 [95% CI: 0.63-0.94] vs lower eGFR/low-dose stratum: rate ratio: 0.87 [95% CI: 0.74-1.03]; P for interaction = 0.34). Consistent benefits were observed for the components of the primary outcome and all-cause death. Safety was also consistent between dosing strata, except for hypokalemia, where the reduction in the odds of hypokalemia with finerenone compared to placebo was greater in the higher eGFR/high-dose stratum (P-interaction < 0.01). CONCLUSIONS: In FINEARTS-HF, an eGFR-based dosing strategy allowed effective and safe use of finerenone in patients with heart failure with mildly reduced ejection fraction/ heart failure with preserved ejection fraction with a baseline eGFR as low as 25&#x2009;mL/min/1.73&#x2009;m2. We recommend that clinicians implement the trial-validated dosing strategy and incorporate appropriate uptitration to the target dose to ensure optimal therapeutic outcomes. (FINEARTS-HF [Study to Evaluate the Efficacy (Effect on Disease) and Safety of Finerenone in Participants With Heart Failure and Left Ventricular Ejection Fraction (Proportion of Blood Expelled Per Heart Stroke) Greater or Equal to 40%; NCT04435626).

Aged↗
PubMed2025

Finerenone and Atrial Fibrillation in Heart Failure: A Secondary Analysis of the FINEARTS-HF Randomized Clinical Trial.

IMPORTANCE: Heart failure (HF) with mildly reduced or preserved ejection fraction and atrial fibrillation (AF) are closely intertwined. OBJECTIVE: To examine the efficacy and safety of the nonsteroidal mineralocorticoid receptor antagonist finerenone in patients with HF with mildly reduced or preserved ejection fraction according to the absence or presence of AF and the type of AF (paroxysmal vs persistent or permanent). DESIGN, SETTING, AND PARTICIPANTS: Prespecified analyses were conducted in the Finerenone Trial to Investigate Efficacy and Safety Superior to Placebo in Patients With Heart Failure (FINEARTS-HF) randomized clinical trial. The trial was conducted across 653 sites in 37 countries. Participants were adults aged 40 years and older with symptomatic HF and left ventricular ejection fraction of 40% or greater, randomized between September 2020 and January 2023. Data analysis was conducted from September 1 to October 1, 2024. INTERVENTION: Finerenone (titrated to 20 mg or 40 mg) or placebo. MAIN OUTCOMES AND MEASURES: The primary outcome was the composite of total HF events and cardiovascular death. New-onset AF or atrial flutter (AFL) was a prespecified exploratory outcome. RESULTS: Among 5984 patients (mean [SD] age, 72.0 [9.6] years; 2724 [45.5%] female) with known AF status at baseline, 1384 (23.1%) had paroxysmal AF and 1886 (31.5%) had persistent or permanent AF. Patients with both types of AF were older and had worse HF status compared with those without AF (2714 patients [45.4%]). Both types of AF were associated with a higher unadjusted risk of the primary outcome compared with no AF (event rate per 100 person-years of follow-up, 20.3 [95% CI, 17.9-23.1] with paroxysmal AF, 19.8 [95% CI, 17.8-22.0] with persistent or permanent AF, and 11.9 [95% CI, 10.7-13.3] with no AF; rate ratio [RR], 1.62 [95% CI, 1.37-1.92] with paroxysmal AF and 1.66 [95% CI, 1.43-1.93] with persistent or permanent AF vs no AF); however, the associations were attenuated after adjustment for known prognostic variables. The benefit of finerenone on the primary outcome (overall RR, 0.84 [95% CI, 0.74-0.95]) was not modified by baseline AF status (RR, 0.80 [95% CI, 0.65-0.98] with no AF, 0.83 [95% CI, 0.65-1.06] with paroxysmal AF, and 0.85 [95% CI, 0.69-1.05] with persistent or permanent AF; P for interaction&#x2009;=&#x2009;.94). New-onset AF or AFL occurred in 6.5% of patients and was associated with a higher subsequent adjusted risk of the primary outcome (rate ratio, 3.65 [95% CI, 2.57-5.18]; P&#x2009;<&#x2009;.001). The subdistribution hazard ratio for new-onset AF or AFL among those receiving finerenone vs placebo was 0.77 (95% CI, 0.57-1.04; P&#x2009;=&#x2009;.09). CONCLUSIONS AND RELEVANCE: The efficacy of finerenone was consistent regardless of AF status. New-onset AF was associated with a substantially higher risk of subsequent outcomes. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04435626.

Humans↗