Biomedical subjects

Kirsty McDowell

Publications and source records attributed to Kirsty McDowell.

3 recordsLinked to original sources

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↗

PubMed2025

Cellular Adhesion Molecules and Adverse Outcomes in Chronic Heart Failure: Findings From the DAPA-HF Randomized Clinical Trial.

IMPORTANCE: Vascular cell adhesion molecule 1 (VCAM-1) and intracellular cell adhesion molecule 1 (ICAM-1) are responsible for immune cell-cell interactions. Systemic levels of VCAM-1 are associated with incident heart failure (HF). OBJECTIVES: To determine if VCAM-1 and ICAM-1 levels are associated with progression of established HF. DESIGN, SETTING, AND PARTICIPANTS: Participants enrolled in the biomarker substudy of the Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure (DAPA-HF) randomized clinical trial had VCAM-1 and ICAM-1 levels measured at baseline and 12 months. The DAPA-HF trial was conducted at 410 sites in 20 countries. Patients with HF and reduced ejection fraction (HFrEF) in New York Heart Association (NYHA) class II to IV with elevated natriuretic peptides were enrolled between February 15, 2017, and August 17, 2018, with final follow-up on June 6, 2019. Data were analyzed from January 2023 to January 2025. INTERVENTIONS: Dapagliflozin, 10 mg, once daily vs placebo. MAIN OUTCOMES AND MEASURES: The primary outcome was the composite of a worsening HF event or cardiovascular death. The associations between VCAM-1 and ICAM-1 levels at baseline and the primary outcome, its components, and all-cause death were analyzed using Cox proportional hazards regression models adjusted for known prognostic variables including estimated glomerular filtration rate (eGFR), N-terminal pro-B-type natriuretic peptide (NT-proBNP), and high-sensitivity troponin T (hs-TnT), as well as high-sensitivity C-reactive protein. RESULTS: A total of 3051 participants (mean [SD] age, 67.2 [10.5] years; 2386 male [78.2%]) were included in this study. Mean (SD) follow-up time was 17.6 (5.2) months. The median (IQR) baseline VCAM-1 level was 997 (816.7-1218.8) ng/mL. Compared with patients with lower concentrations of VCAM-1, those with higher concentrations of VCAM-1 were older (mean [SD] age T3 vs T1, 69.7 [9.7] years vs 64.1 [10.7] years; P < .001), in worse NYHA class (T3 vs T1, NYHA class III/IV 35.6% [362 of 1017] vs 26.5% [269 of 1017]; P < .001), and had higher NT-proBNP (median [IQR] T3 vs T1, 2018 [1126-3753] pg/mL vs 1118 [693-1830] pg/mL) and hs-TnT (median [IQR] T3 vs T1, 24.7 [17.1-37.5] ng/L vs 16.6 [11.6-24.9] ng/L) concentrations, and lower eGFR (mean [SD] T3 vs T1, 58.4 [17.6] mL/min/1.73 m2 vs 71.7 [18.0] mL/min/1.73 m2). Patients in tertile 3 of VCAM-1, compared with tertile 1, had the highest risk of each outcome (eg, adjusted hazard ratio [HR] for primary outcome 1.40; 95% CI, 1.11-1.77; P = .004). ICAM-1 level was not associated with an elevated risk of any outcome. The benefit of dapagliflozin vs placebo in reducing the risk of the primary outcome was consistent across VCAM-1 tertiles: HR, 0.76 (95% CI, 0.54-1.06), 0.82 (95% CI, 0.59-1.12), and 0.77 (95% CI, 0.61-0.98) for tertiles 1, 2 and 3, respectively (P for interaction = .93). There was no significant change in VCAM-1 level with dapagliflozin at 52 weeks. CONCLUSIONS AND RELEVANCE: Results of this substudy of the DAPA-HF randomized clinical trial demonstrate that higher VCAM-1 levels, possibly reflecting a distinct inflammatory/immune pathophysiological pathway in HFrEF, were associated with worse outcomes, even after adjustment for conventional prognostic variables. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03036124.

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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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