Biomedical subjects

James Lay-Flurrie

Publications and source records attributed to James Lay-Flurrie.

8 recordsLinked to original sources

PubMed2026

Finerenone and quality of life in heart failure: component-level analyses and clinical relevance of the Kansas City cardiomyopathy questionnaire.

AIMS: Finerenone was shown to improve overall health status, as measured by the aggregate 23-item Kansas City Cardiomyopathy Questionnaire (KCCQ) score, in heart failure with mildly reduced or preserved ejection fraction (HFmrEF/HFpEF). This study aimed to contextualize KCCQ changes in a manner that is relevant to patients and clinicians, thereby improving understanding of this metric in HFmrEF/HFpEF. METHODS AND RESULTS: In this prespecified analysis of FINEARTS-HF, a double-blind, randomized, placebo-controlled trial of finerenone in HFmrEF/HFpEF, we performed exploratory assessments of treatment effects on mean score changes from baseline to 12 months for each of the 23 KCCQ components (scaled from 0 [worst] to 100 [best]) using multivariable linear regression. We further compared the impact of finerenone on the KCCQ-overall summary score (KCCQ-OSS) at 12 months with the expected decline per year. Of 6001 participants in FINEARTS-HF, 5006 completed the KCCQ both at baseline and 12 months (age: 72 ± 10 years, women: 45%, baseline KCCQ-OSS: 63.9 ± 22.0). Finerenone, compared with placebo, numerically improved all but one KCCQ component, with the greatest nominal improvement observed in lower limb oedema frequency (+2.5, 95% CI: 0.9-4.1), fatigue burden (+2.2, 95% CI: 0.9-3.5), fatigue frequency (+2.1, 95% CI: 0.7-3.6), and lower limb oedema burden (+1.8, 95% CI: 0.6-2.9). KCCQ-OSS at 12 months was inversely related to age, with finerenone shifting the age-KCCQ-OSS relationship by 4.7 (95% CI: 0.4-9.1) years. CONCLUSIONS: In FINEARTS-HF, finerenone was associated with modest improvements in health status-most notably lower limb oedema and fatigue-in patients with HFmrEF/HFpEF.

Humans↗

PubMed2026

EMPEROR-Preserved Risk Model and Outcomes in the FINEARTS-HF Trial: A Prespecified Secondary Analysis of FINEARTS-HF.

IMPORTANCE: Patients with heart failure (HF) and mildly reduced ejection fraction (HFmrEF) or preserved EF (HFpEF) show substantial heterogeneity in prognosis. OBJECTIVES: To evaluate the performance of biomarker-driven prognostic models derived from the Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Preserved Ejection Fraction (EMPEROR-Preserved) Trial in the Finerenone Trial to Investigate Efficacy and Safety Superior to Placebo in Patients With Heart Failure (FINEARTS-HF) and to examine whether baseline risk modified the therapeutic effect of finerenone. DESIGN, SETTING, AND PARTICIPANTS: This is a prespecified secondary analysis of the FINEARTS-HF trial, which was conducted across 653 sites in 37 countries among adults aged 40 years and older with symptomatic HF and left ventricular EF (LVEF) of 40% or greater. Patients were randomized between September 2020 and January 2023, and data analysis for this study was conducted from September to October 2025. The median (IQR) follow-up period was 32 (23-37) months. INTERVENTION: Finerenone (titrated to 20 mg or 40 mg) or placebo. MAIN OUTCOMES AND MEASURES: EMPEROR-Preserved risk scores for the outcomes of first HF hospitalization or cardiovascular death, cardiovascular death, and all-cause death were calculated in FINEARTS-HF using models incorporating N-terminal pro-B-type natriuretic peptide, high-sensitivity cardiac troponin T, New York Heart Association functional class, history of chronic obstructive pulmonary disease and diabetes, insulin use, and-depending on outcome-age, hemoglobin and albumin levels, HF duration, time from prior HF hospitalization, and sodium-glucose transporter 2 inhibitor use. Estimated risks were compared with observed event rates, and model performance was assessed using Harrell C statistic. Treatment effects were evaluated across risk quintiles (Q1 to Q5) and across the continuous risk distribution. RESULTS: Among 6001 patients (mean [SD] age, 72.0 [9.6] years; 2732 [45.5%] women; 3003 randomized to finerenone and 2998 randomized to placebo), the EMPEROR-Preserved risk model estimated risk of outcomes, with Q5 vs Q1 hazard ratios (HRs) of 10.49 (95% CI, 8.14-13.52) for the composite of HF hospitalization or cardiovascular death and 13.47 (95% CI, 8.79-20.64) for cardiovascular death. The model demonstrated good discrimination. The treatment effect of finerenone was consistent across risk quintiles for first HF hospitalization or cardiovascular death (Q1: HR, 0.93 [95% CI, 0.58-1.49]; Q2: HR, 1.04 [95% CI, 0.76-1.43]; Q3: HR, 0.82 [95% CI, 0.62-1.07]; Q4: HR, 0.81 [95% CI, 0.65-1.01]; and Q5: HR, 0.88 [95% CI, 0.74-1.05]; P for interaction = .68) and remained uniform across the continuous risk spectrum. CONCLUSIONS AND RELEVANCE: The EMPEROR-Preserved risk models demonstrated good performance in FINEARTS-HF. Baseline risk did not modify the relative treatment effect of finerenone. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04435626.

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 mL/min/1.73 m2 at baseline were stratified at randomization to the low-dose group and started on 10 mg of finerenone once daily (titrated to a maximum 20 mg/d) or matching placebo, whereas those with an eGFR >60 mL/min/1.73 m2 at baseline were stratified to the high-dose group and started on 20 mg of finerenone once daily (titrated to a maximum 40 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 ± SD achieved dose was 32.3 ± 9.1 mg (finerenone) and 34.4 ± 7.8 mg (placebo) in the higher eGFR/high-dose stratum, and 15.6 ± 4.3 mg (finerenone) and 16.7 ± 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 mL/min/1.73 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).

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PubMed2025

Finerenone According to Frailty in Heart Failure: A Prespecified Analysis of the FINEARTS-HF Randomized Clinical Trial.

IMPORTANCE: Patients with frailty are often perceived to have a less favorable benefit-risk profile for novel therapies and therefore may be less likely to receive these. OBJECTIVE: To examine the efficacy and safety of finerenone, compared with placebo, according to frailty status in patients with heart failure (HF) and mildly reduced ejection fraction (HFmrEF) or with HF and preserved ejection fraction (HFpEF). DESIGN, SETTING, AND PARTICIPANTS: This was a prespecified secondary analysis of a phase 3 randomized clinical trial, the Finerenone Trial to Investigate Efficacy and Safety Superior to Placebo in Patients With Heart Failure (FINEARTS-HF), conducted across 653 sites in 37 countries. Patients with HF with New York Heart Association functional class II through IV, a left ventricular ejection fraction of 40% or higher, evidence of structural heart disease, and elevated natriuretic peptide levels were randomized between September 2020 and January 2023. Data analysis was conducted from October 1 to November 30, 2024. INTERVENTION: Addition of once-daily finerenone or placebo to usual therapy. MAIN OUTCOMES AND MEASURES: The primary outcome was a composite of cardiovascular death and total worsening HF events. Frailty was measured using the Rockwood cumulative deficit approach. RESULTS: Of the 6001 patients randomized in FINEARTS-HF, a frailty index (FI) was calculable in 5952 patients (mean [SD] age, 72.0 [9.6] years; 3241 [54.4%] male). In total, 1588 patients (26.7%) had class I frailty (FI ≤0.210 [not frail]), 2141 (36.0%) had class II frailty (FI 0.211-0.310 [more frail]), and 2223 (37.3%) had class III frailty (FI ≥0.311 [most frail]). Compared with patients with class I frailty, those with class II and III frailty had a higher risk of the primary outcome (unadjusted rate ratio [RR], 1.88 [95% CI, 1.54-2.28] for class II and 3.86 [95% CI, 3.22-4.64] for class III). The effect of finerenone on the primary outcome did not vary significantly by frailty class (class I: RR, 1.07 [95% CI, 0.77-1.49]; class II: RR, 0.66 [95% CI, 0.52-0.83]; class III: RR, 0.91 [95% CI, 0.76-1.07]; P for interaction = .77). Frailty class did not modify the effects of finerenone on the components of the primary outcome, all-cause death, or improvement in the Kansas City Cardiomyopathy Questionnaire total symptom score. The effects of finerenone, compared with placebo, on experiencing hypotension, elevated creatinine level, hyperkalemia, or hypokalemia did not differ by frailty class. CONCLUSIONS AND RELEVANCE: In FINEARTS-HF, finerenone reduced the risk of total worsening HF events and cardiovascular death, and it improved symptoms; these effects were not modified by frailty status. In addition, the effects of finerenone on experiencing hypotension, elevated creatinine level, hyperkalemia, or hypokalemia did not differ by frailty status. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04435626.

Humans↗

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 = .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 < .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 = .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↗

PubMed2025

Mode of Death in Patients With Heart Failure With Mildly Reduced or Preserved Ejection Fraction: The FINEARTS-HF Randomized Clinical Trial.

IMPORTANCE: The mode of death in patients with heart failure with mildly reduced ejection fraction (HFmrEF) or heart failure with preserved ejection fraction (HFpEF) remains poorly understood and may vary by EF. OBJECTIVE: To evaluate the mode of death according to EF and the treatment effect of finerenone on cause-specific mortality in patients with HFmrEF/HFpEF. DESIGN, SETTING, AND PARTICIPANTS: This was a prespecified secondary analysis of the Finerenone Trial to Investigate Efficacy and Safety Superior to Placebo in Patients With Heart Failure (FINEARTS-HF) randomized clinical trial, which evaluated clinical outcomes in 6001 patients with HF and EF greater than or equal to 40% randomly assigned to finerenone or placebo. The mode of death in relation to baseline EF categories (<50%, ≥50-<60%, and ≥60%) was examined, and the effect of randomized treatment on cause-specific death in Cox regression models was assessed. Data analysis was conducted between September 2024 and January 2025. INTERVENTIONS: Finerenone vs placebo. MAIN OUTCOMES AND MEASURES: Mode of death as centrally adjudicated by a clinical end points committee. RESULTS: Of 1013 patients (16.9%; median [IQR] age, 76 [69-82] years; 594 male [58.6%]) who died during median (IQR) follow-up of 32 (23-36) months, mode of death was ascribed to cardiovascular causes in 502 (49.6%), noncardiovascular causes in 368 (36.3%), and undetermined cause in 143 (14.1%). Of cardiovascular deaths, 215 (42.8%) were due to sudden death, 163 (32.4%) to HF, 48 (9.6%) to stroke, 25 (5.0%) to myocardial infarction, and 51 (10.2%) to other cardiovascular causes. The proportion of all-cause, cardiovascular, and sudden death was higher in those with EF less than 50%. The proportion of deaths related to HF was similar across EF categories, and the proportion of deaths due to myocardial infarction, stroke, and other cardiovascular causes was low regardless of EF. Randomization to finerenone did not significantly reduce death or cause-specific death compared with placebo in any EF category. CONCLUSIONS AND RELEVANCE: Among patients with HFmrEF/HFpEF in the FINEARTS-HF randomized clinical trial, higher proportions of cardiovascular and overall mortality in those with EF less than 50% were related principally to higher proportions of sudden death. A clear treatment effect of finerenone on cardiovascular or cause-specific mortality was not identified, although the trial was likely underpowered for these outcomes. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04435626.

Humans↗

PubMed2025

Finerenone for Heart Failure and Risk Estimated by the PREDICT-HFpEF Model: A Secondary Analysis of FINEARTS-HF.

IMPORTANCE: Patients with heart failure (HF) and mildly reduced ejection fraction (HFmrEF) or preserved ejection fraction (HFpEF) have a spectrum of risk, and the effect of therapies may vary by risk. OBJECTIVES: To validate the Prognostic Models for Mortality and Morbidity in HFpEF (PREDICT-HFpEF) in the phase 3 randomized clinical trial Finerenone Trial to Investigate Efficacy and Safety Superior to Placebo in Patients With Heart Failure (FINEARTS-HF) and to evaluate the effect of finerenone, compared with placebo, across the spectrum of risk in these patients. DESIGN, SETTING, AND PARTICIPANTS: The FINEARTS-HF trial was conducted across 653 sites in 37 countries. Participants were adults 40 years and older with symptomatic HF and left ventricular EF of 40% or greater randomized between September 2020 and January 2023. INTERVENTION: Finerenone (titrated to 20 mg or 40 mg) or placebo. MAIN OUTCOMES AND MEASURES: The 3 PREDICT-HFpEF risk scores for the composite outcome of cardiovascular death or HF hospitalization, cardiovascular death, and all-cause death, respectively, were calculated. Predicted risk was compared with observed outcomes. Model performance was assessed using the Harrell C statistic. The rates of the predicted outcomes (plus the composite of cardiovascular death and worsening HF events, which was the primary end point in the trial) were examined according to quintiles of risk score, as was the effect of finerenone according to risk quintiles. RESULTS: A total of 6001 patients (mean [SD] age, 72 [9.6] years; 3269 male [54.5%]) were randomized in the FINEARTS-HF trial. The C statistics for cardiovascular death or HF hospitalization, cardiovascular death, and all-cause death at 2 years were 0.71 (95% CI, 0.69-0.72), 0.68 (95% CI, 0.66-0.71), and 0.69 (95% CI, 0.67-0.71), respectively. The risk of the composite outcomes was approximately 8- to 10-fold higher in those in the highest compared with the lowest risk quintile. The relative risk reduction with finerenone compared with placebo was consistent across the spectrum of risk for all outcomes examined (eg, interaction P value for primary outcome = .24). CONCLUSIONS AND RELEVANCE: Results of the FINEARTS-HF randomized clinical trial demonstrate that the PREDICT-HFpEF models performed well in terms of calibration and discrimination. Baseline risk did not modify the benefit of finerenone. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04435626.

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PubMed2025

Estimated Long-Term Benefits of Finerenone in Heart Failure: A Prespecified Secondary Analysis of the FINEARTS-HF Randomized Clinical Trial.

IMPORTANCE: People living with heart failure (HF) with mildly reduced or preserved ejection fraction have substantially curtailed life expectancy free from clinical events compared with their peers of comparable age. The nonsteroidal mineralocorticoid receptor antagonist, finerenone, was recently shown to reduce risks of cardiovascular events in this population over a median follow-up of 2.6 years; as patients with HF typically continue treatment beyond this time frame, estimating the potential long-term benefits of finerenone could inform shared clinical decision-making. OBJECTIVE: To estimate the projected long-term treatment effects of finerenone in patients with HF with mildly reduced or preserved ejection fraction if treated over a patient's lifetime. DESIGN, SETTING, AND PARTICIPANTS: Prespecified analyses were conducted of the FINEARTS-HF trial, a phase 3 randomized clinical trial conducted across 653 sites in 37 countries. Adults 40 years and older with symptomatic HF and left ventricular ejection fraction of 40% or greater were randomized from September 2020 to January 2023. Median (IQR) follow-up was 2.6 (1.9-3.0) years. INTERVENTIONS: Finerenone (titrated to either 20 mg or 40 mg) or placebo. MAIN OUTCOMES AND MEASURES: The primary composite outcome was time to cardiovascular death or worsening HF event. The long-term gains in survival free from a primary end point with finerenone were iteratively estimated with age-based Kaplan-Meier curves using age at randomization rather than time from randomization. Differences in areas under the survival curves between the finerenone and placebo arms represented event-free survival gains. RESULTS: Among 6001 participants (median [IQR] age, 73 [66-79] years; 3269 male [54.5%]), mean survival free from the primary end point for a 55-year-old participant was 13.6 years (95% CI, 11.9-15.2 years) with finerenone and 10.5 years (95% CI, 6.8-11.3 years) with placebo, representing a gain in event-free survival of 3.1 years (95% CI, 0.8-5.4 years; P = .007). Mean event-free survival for a 65-year-old participant was 11.0 years (95% CI, 10.1-11.9 years) with finerenone and 8.9 years (95% CI, 8.1-9.8 years) with placebo, representing a gain of 2.0 years (95% CI, 0.8-3.3 years; P = .001). Projected mean event-free survival was numerically greater with finerenone than with placebo for every starting age between 50 to 80 years. Lifetime gains in event-free survival were observed even among individuals already treated with a sodium-glucose cotransporter 2 inhibitor (65-year-old participant: 3.1 years; 95% CI, 0.1-6.0 years; P = .04). CONCLUSIONS AND RELEVANCE: In this prespecified secondary analysis of the FINEARTS-HF randomized clinical trial, long-term treatment with finerenone was estimated to extend event-free survival by up to 3 years among people with HF with mildly reduced or preserved ejection fraction. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04435626.

Humans↗