Biomedical subjects

Brian L Claggett

Publications and source records attributed to Brian L Claggett.

At least 19 recordsLinked to original sources

PubMed2027

Effectiveness of high-dose versus standard-dose influenza vaccines against hospitalisation according to frailty risk: a prespecified analysis of the randomised trial DANFLU-2.

BACKGROUND: Frailty is a major risk factor for influenza-related complications and can influence vaccine effectiveness. We aimed to assess the relative vaccine effectiveness (rVE) of high-dose (HD-IIV) versus standard-dose inactivated influenza vaccine (SD-IIV) in older adults aged 65 years or older according to frailty risk. METHODS: This study was a prespecified analysis of DANFLU-2, an open-label, individually randomised trial, conducted in Denmark during three consecutive influenza seasons (2022-23, 2023-24, and 2024-25). Adults aged 65 years or older were randomised (1:1) to the HD-IIV or SD-IIV group. The primary endpoint was hospitalisation for influenza or pneumonia. Frailty was defined according to the validated Hospital Frailty Risk Score (HFRS) based on ICD-10 codes within 10 years before randomisation. Participants were stratified into three HFRS categories, namely low (<5 points), intermediate (5-15 points), and high (>15 points) frailty risk. The rVE of HD-IIV versus SD-IIV against the primary endpoint was assessed across prespecified HFRS categories and treating HFRS as a continuous variable. Pearson's chi-square test was used to compare safety events across frailty risk groups and randomisation groups. FINDINGS: Among 332 438 randomised participants (mean age 73·7 years [SD 5·8]; 161 538 [48·6%] were female), 276 173 (83·1%) had low frailty risk, 52 395 (15·8%) had intermediate frailty risk, and 3861 (1·2%) had high frailty risk. The primary endpoint of hospitalisation for influenza or pneumonia occurred in 1424 (0·5%) of 276 173 participants with low frailty risk, 761 (1·5%) of 52 395 with intermediate frailty risk, and 163 (4·2%) of 3861 with high frailty risk (relative risk [RR] for intermediate vs low frailty risk 2·8 [95% CI 2·6-3·1]; RR for high vs low frailty risk 8·2 [7·0-9·6]). HFRS as a continuous variable significantly modified the effect of HD-IIV versus SD-IIV against the primary endpoint with higher rVE estimates with increasing HFRS (pinteraction=0·020). The rVE was 0·2% (95% CI -10·8 to 10·2) among those with low frailty risk, 13·1% (-0·4 to 24·8) among those with intermediate frailty risk, and 19·9% (-10·3 to 42·1) among those with high frailty risk. No significant interaction was observed when HFRS was assessed according to the prespecified categorical frailty groups (pinteraction=0·17). The proportion of participants with at least one serious adverse event increased across frailty risk groups (13 366 [4·8%] of 275 795 for low frailty risk, 5475 [10·5%] of 52 315 for intermediate frailty risk, and 777 [20·2%] of 3850 for high frailty risk; p<0·0001), with similar proportions of serious adverse events in the HD-IIV and SD-IIV groups for each frailty risk group. INTERPRETATION: Among adults aged 65 years or older in Denmark, frailty risk might modify the effects of HD-IIV versus SD-IIV against hospitalisation for influenza or pneumonia, with higher rVE estimates with increasing frailty risk. These findings might support considering high-dose influenza vaccines for frail older adults. However, effect modification was not evident when frailty was assessed using prespecified categorical subgroups, and subgroup-specific estimates were imprecise, with 95% CIs crossing the null. These results should be considered exploratory, warranting further investigation. FUNDING: The DANFLU-2 trial was funded by Sanofi.

Journal Article↗

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

Spironolactone, early acute eGFR changes, and clinical outcomes in patients with heart failure with preserved ejection fraction: insights from TOPCAT Americas.

AIMS: Early acute changes in estimated glomerular filtration rate (eGFR) have been well described with renin-angiotensin system inhibitors and sodium-glucose cotransporter-2 inhibitors, but less is known about the frequency, prognostic relevance, and implications of these changes after mineralocorticoid receptor antagonist (MRA) initiation in patients with heart failure with preserved ejection fraction (HFpEF). METHODS: We performed a post-hoc analysis of 1648 patients enrolled in the TOPCAT trial (Americas regional subgroup), defining an early eGFR dip as a ≥15% decrease in eGFR between baseline and week 4. Landmark analyses assessed the association of eGFR changes, treatment, and the primary composite endpoint (cardiovascular death, HF hospitalization, or aborted cardiac arrest). RESULTS: Within 4 weeks of treatment initiation, 431 (26%) patients experienced acute eGFR decrease with a higher proportion of patients assigned to spironolactone [269 (33%)] compared with placebo [162 (20%)] (odds ratio 1.97; 95% confidence interval 1.58-2.47). An acute eGFR decrease was independently associated with higher risk of subsequent cardiovascular outcomes, irrespective of treatment arm. However, treatment with spironolactone appeared beneficial in reducing the primary cardiovascular outcome irrespective of the presence [hazard ratio 0.75 (0.53-1.08)] or absence [0.80 (0.64-1.00)] of early eGFR decrease (Pinteraction = .81). At any given magnitude of eGFR decline, risk of the primary endpoint was consistently lower with spironolactone compared with placebo (Pinteraction = .64). CONCLUSIONS: Early acute eGFR changes were common and adversely prognostic in patients with HFpEF. Spironolactone treatment was beneficial in improving cardiovascular outcomes, despite a modest increase in the likelihood of acute eGFR decrease. An acute eGFR decrease early after MRA initiation should not automatically prompt treatment discontinuation. TRIAL REGISTRATION: ClinicalTrials.gov NCT00094302.

Humans↗

PubMed2026

Electronic Nudges to Increase Influenza Vaccination in Immunosuppressed Adults Across the Age Spectrum: A Pooled Analysis of 2 Nationwide Randomized Trials.

BACKGROUND: Immunosuppressed individuals face higher risk of severe influenza complications, yet vaccination coverage remains low. We aimed to assess the effect of electronic letter-based nudges on influenza vaccination uptake by immunosuppression status. METHODS: We performed a participant-level pooled analysis of 2 methodologically harmonized, nationwide, pragmatic randomized clinical trials during the 2023-2024 influenza season. Adults aged ≥65 years (NUDGE-FLU-2) and adults aged 18-64 years with chronic conditions (NUDGE-FLU-CHRONIC) were included, with immunosuppression defined by an immunosuppressive diagnosis or a filled prescription for immunosuppressive therapy. Participants were randomized in a 2.45:1:1:1:1:1:1 ratio to usual care or 1 of 6 electronic letter interventions. The primary outcome was receipt of influenza vaccination by 1 January 2024 ascertained from nationwide administrative health registries. Effect modification by immunosuppression status was assessed using binomial regression. RESULTS: Among 1 181 254 participants (mean age 67 years; 73 830 [6.3%] immunosuppressed), 66.1% were vaccinated. Any letter increased vaccine uptake compared with usual care (absolute difference, 2.79% points; 95% confidence interval [CI], 2.60-2.98; P < .001), with greater effect among immunosuppressed individuals (+4.12 vs +2.70% points; Pinteraction = .002). In younger adults with chronic conditions, letter-based nudges increased vaccination rates by 11.7% points overall and by 13.3% points among those with immunosuppression (Pinteraction = .007). Among immunosuppressed individuals, nudging effects appeared greater for those with immunosuppressive conditions than for those receiving immunosuppressive treatment. CONCLUSIONS: Electronic letter-based nudges increased influenza vaccination rates, with greater benefit among immunosuppressed individuals. These findings support implementation of low-cost, letter-based nudging strategies to improve vaccine uptake in this high-risk population. Clinical Trials Registration. NCT06030726 and NCT06030739.

Adolescent↗

PubMed2026

Large Language Model Recommendations for Heart Failure Therapy.

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Heart failure↗

PubMed2026

Geographic Variation in Heart Failure With Mildly Reduced or Preserved Ejection Fraction: Insights From the FINEARTS-HF Trial.

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clinical trials↗

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

Spectrum of Primary Aldosteronism and Risk of Cardiovascular Outcomes: The Atherosclerosis Risk in Communities Study.

IMPORTANCE: Mounting evidence suggests that renin-independent aldosteronism is common and often underrecognized. Yet, whether aldosteronism across this broader spectrum is associated with incident cardiovascular disease (CVD) has not, to the authors' knowledge, been comprehensively evaluated. OBJECTIVE: To determine whether aldosterone measures are associated with incident CVD events in community-dwelling older adults. DESIGN, SETTING, AND PARTICIPANTS: This prospective cohort analysis included participants from the Atherosclerosis Risk in Communities (ARIC) study with serum aldosterone and renin levels measured in 2011 to 2013. Longitudinal analyses were conducted in March to September 2025 using Cox regression to assess associations between aldosterone parameters and incident CVD among participants free of heart failure (HF), myocardial infarction (MI), stroke, and potassium-sparing diuretic use at ARIC visit 5 (2011-2013). EXPOSURES: Serum aldosterone level and aldosterone-renin ratio (ARR). MAIN OUTCOMES AND MEASURES: Incident HF hospitalization, atrial fibrillation (AF), ischemic stroke, MI, and a composite of these events plus all-cause death. RESULTS: Among 3477 individuals free of baseline CVD (mean [SD] age, 74.8 [4.9] years; 2139 female [61.5%]), the median (IQR) aldosterone level was 5.1 (3.0-8.3) ng/dL (to convert to picomoles per liter, multiply by 27.74), renin activity was 0.78 (0.41-1.90) ng/mL per hour, and ARR was 5.9 (2.2-12.3) ng/dL per ng/mL/h. Over 9 years of follow-up, higher ARR was associated with the composite outcome (adjusted hazard ratio [aHR], 1.04; 95% CI, 1.01-1.08 per doubling), stroke (aHR, 1.13; 95% CI, 1.02-1.26), and AF (aHR, 1.10; 95% CI, 1.05-1.15) but not with incident HF hospitalization (aHR, 1.02; 95% CI, 0.96-1.07) or MI (aHR, 1.01; 95% CI, 0.92-1.12). CONCLUSIONS AND RELEVANCE: The findings of this cohort study underscore a spectrum of primary aldosteronism, in which higher ARR was independently associated with increased risks of AF and ischemic stroke among older adults, supporting the aldosterone pathway as a potential target for CVD prevention.

Humans↗

PubMed2026

Effects of Finerenone on Heart Failure Outcomes According to Baseline Heart Failure Risk in Chronic Kidney Disease and Type 2 Diabetes.

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chronic kidney disease↗

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).

Aged↗

PubMed2026

Social Determinants of Health and Clinical Outcomes in Hypertrophic Cardiomyopathy.

IMPORTANCE: Area-based indicators of social determinants of health (SDOH) are associated with higher risk for acquired heart disease, but their impact on conditions with a strong genetic etiology, such as hypertrophic cardiomyopathy (HCM), is not well understood. OBJECTIVE: To determine the association of area-based SDOH with clinical outcomes in patients with HCM. DESIGN, SETTING, AND PARTICIPANTS: This multicenter, prospective cohort study was conducted among US adult patients with HCM from 5 sites in the Sarcomeric Human Cardiomyopathy Registry (a multicenter prospective registry of patients with HCM) who were followed up for a median (IQR) period of 2.15 (0.15-5.82) years. Data were entered from 2015 to March 2024, and data analysis was completed from March 2024 to June 2025. EXPOSURES: Patients' residential addresses were geocoded at the zip code level and linked to the American Communities Survey to estimate area-based (1) median household income and (2) social deprivation index (SDI), which ranges from 0 to 100, with higher scores indicating a more deprived area. MAIN OUTCOMES AND MEASURES: Multivariate models, adjusting for age at diagnosis, body mass index, hypertension, and sex, were used to estimate the independent association of area-based median household income and SDI with heart failure (HF), ventricular arrhythmias (VA), and an overall composite outcome (VA, HF, atrial fibrillation, stroke, and death). RESULTS: Among 4431 US adult patients with HCM, median (IQR) age at HCM diagnosis was 51.3 (38.9-61.6) years, and 1862 patients (42.0%) were female. Median (IQR) area-based household income was $80 000 ($60 000-$110 000), and median (IQR) SDI was 25 (10-55). Adjusted hazard ratios comparing the lowest income group to the highest income group were 2.07 (95% CI, 1.77-2.42; P < .001) for HF, 1.31 (95% CI, 0.97-1.78; P = .08) for VA, and 1.52 (95% CI, 1.36-1.69; P < .001) for the overall composite outcome. Adjusted hazard ratios comparing the highest SDI (ie, more deprived) group to the lowest SDI group were 1.48 (95% CI, 1.29-1.70; P < .001) for HF, 1.55 (95% CI, 1.15-2.09; P = .004) for VA, and 1.36 (95% CI, 1.22-1.50; P < .001) for the overall composite outcome. CONCLUSIONS AND RELEVANCE: In this multicenter cohort study, residing in an area with lower median household income or worse SDI were each independently associated with adverse clinical outcomes in patients with HCM. These findings suggest that despite the genetically determined nature of HCM, place of residence is associated with patient outcomes.

Humans↗

PubMed2025

Finerenone-Related Risk of Hypotension in Heart Failure With Mildly Reduced or Preserved Ejection Fraction.

BACKGROUND: The nonsteroidal mineralocorticoid receptor antagonist finerenone reduces clinical events in heart failure with mildly reduced ejection fraction/preserved ejection fraction; however, the implications of treatment-related hypotension are unknown. OBJECTIVES: The authors investigated predictors of systolic blood pressure (SBP) <100 mm Hg and investigator-reported hypotension and their associations with randomized treatment and clinical outcomes in the 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]) trial. METHODS: FINEARTS-HF was a randomized, placebo-controlled trial of finerenone in symptomatic patients with chronic heart failure (left ventricular ejection fraction ≥40%). Predictors of SBP <100 mm Hg and hypotension were identified using Cox models. Associations between SBP <100 mm Hg and hypotension, treatment, and clinical outcomes were evaluated using time-updated Cox models. The primary outcome was a composite of total heart failure events and cardiovascular death. RESULTS: Among the 5,815 participants with available data, post-baseline SBP <100 mm Hg occurred in 899 (538 with finerenone vs 361 with placebo; odds ratio: 1.60; 95% CI: 1.38-1.85) and investigator-reported hypotension in 364 patients (225 with finerenone vs 139 with placebo; odds ratio: 1.67; 95% CI: 1.34-2.08). Participants experiencing SBP <100 mm Hg had lower baseline SBP, were older, had higher N-terminal pro-B-type natriuretic peptide levels, a history of smoking, and no diabetes. Treatment-related risk of the primary endpoint was reduced in patients with no/before SBP <100 mm Hg (rate ratio: 0.78; 95% CI: 0.67-0.90) and appeared to attenuate afterwards (rate ratio: 0.99; 95% CI: 0.70-1.39), although no formal statistical interaction was observed (Pinteraction = 0.33). CONCLUSIONS: In this prespecified analysis of the FINEARTS-HF trial, finerenone led to higher rates of post-baseline SBP <100 mm Hg and investigator-reported hypotension. Although hypotension should not prompt automatic treatment discontinuation, these patients should be carefully monitored. (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% [FINEARTS-HF]; NCT04435626).

Humans↗

PubMed2025

Finerenone and Cardiovascular Outcomes According to Baseline Kidney Function in Patients With Heart Failure: The FINEARTS-HF Trial.

BACKGROUND: Finerenone is known to reduce the risk of worsening heart failure (HF) events and cardiovascular (CV) death in patients with HF with mildly reduced or preserved ejection fraction. OBJECTIVES: The authors explored whether the benefit of finerenone among patients with HF with mildly reduced or preserved ejection fraction differs according to baseline measures of kidney function. METHODS: FINEARTS-HF (Finerenone Trial to Investigate Efficacy and Safety Superior to Placebo in Patients With Heart Failure) was a global, randomized clinical trial of finerenone vs placebo among patients with HF with mildly reduced or preserved ejection fraction. Finerenone was titrated to 20 mg/d if the estimated glomerular filtration rate (eGFR) was ≤60 mL/min/1.73 m2 or 40 mg/d if eGFR was >60 mL/min/1.73 m2. The authors used a semiparametric proportional rates method, stratified by left ventricular ejection fraction (<60%; ≥60%) and region, to assess for differential treatment effects on the composite of total HF events and CV death according to the baseline eGFR (continuous and categories [≥60 mL/min/1.73 m2, 45 to <60 mL/min/1.73 m2, <45 mL/min/1.73 m2] and urine albumin-creatinine ratio (UACR) (<30 mg/g, 30 to <300 mg/g, ≥300 mg/g). RESULTS: The effect of finerenone to reduce the primary endpoint of total HF events and CV death did not significantly differ according to baseline eGFR (Pinteraction = 0.14 and 0.07 for continuous and categorical eGFR, respectively) with rate ratio 0.72 (95% CI: 0.59-0.88) for eGFR ≥60 mL/min/1.73 m2, 0.83 (95% CI: 0.65-1.06) for eGFR 45 to <60 mL/min/1.73 m2, and 1.02 (95% CI: 0.83-1.26) for eGFR <45 mL/min/1.73 m2. The corresponding absolute event rates were 9.2 vs 12.5, 16.5 vs 19.9, and 28.0 vs 28.0 per 100 patient-years for finerenone vs placebo, respectively. Similar results were noted for total worsening HF events. Finerenone lowered the risk of the composite CV outcome similarly across baseline categories of UACR (Pinteraction = 0.48). CONCLUSIONS: In the FINEARTS-HF trial (where the target dose of finerenone was determined by baseline kidney function), the effect of finerenone to reduce the composite of cardiovascular death and total HF events did not significantly differ across a range of baseline eGFR and UACR.

Humans↗

PubMed2025

High-Dose vs Standard-Dose Influenza Vaccine and Cardiovascular Outcomes in Older Adults: A Prespecified Secondary Analysis of the DANFLU-2 Randomized Clinical Trial.

IMPORTANCE: The high-dose inactivated influenza vaccine (HD-IIV) has demonstrated superior protection against laboratory-confirmed influenza infection vs standard-dose IIV (SD-IIV); however, data regarding its effectiveness against cardiovascular (CV) outcomes are mainly from observational studies or specific high-risk groups. OBJECTIVE: To investigate the relative vaccine effectiveness (rVE) of HD-IIV vs SD-IIV against CV outcomes in the general older adult population in Denmark. DESIGN, SETTING, AND PARTICIPANTS: This was a prespecified secondary analysis of DANFLU-2, a pragmatic, open-label, individually randomized clinical trial (RCT) using nationwide administrative health registries in Denmark during the 2022/2023 to 2024/2025 influenza seasons. Older adults (age ≥65 years) were eligible for inclusion regardless of comorbidity. The trial design specified that if the primary end point was neutral, no hypothesis testing would be performed for secondary or exploratory end points. Data were analyzed from June 29 to August 12, 2025. INTERVENTIONS: Individual-level 1:1 randomization to HD-IIV or SD-IIV. Participants re-enrolling in additional seasons were rerandomized. MAIN OUTCOMES AND MEASURES: Severe CV outcomes were prespecified secondary and exploratory end points in the trial, occurring from 14 days after vaccination through May 31 the following year. RESULTS: A total of 332 438 participants (170 900 [51.4%] male; mean [SD] age, 73.7 [5.8] years) were randomized (166 218 to HD-IIV and 166 220 to SD-IIV), of whom 91 026 (27.4%) had a history of CV disease. HD-IIV did not significantly reduce the trial's primary end point of hospitalization for influenza or pneumonia. The incidence of hospitalization for any cardiorespiratory disease was lower in the HD-IIV group than the SD-IIV group (rVE, 5.7% [95% CI, 1.4% to 9.9%]; absolute difference, -0.13 [95% CI, -0.24 to -0.03] percentage points), and rVE did not differ by history of CV disease compared with no CV disease at baseline. Hospitalization for any CV disease occurred in fewer participants in the HD-IIV group than the SD-IIV group (rVE, 7.5% [95% CI, 1.5% to 12.5%]; absolute difference, -0.10 [95% CI, -0.18 to -0.02] percentage points) as did hospitalization for heart failure (rVE, 19.5% [95% CI, 3.3% to 33.1%]; absolute difference, -0.03 [95% CI, -0.06 to -0.01] percentage points). CONCLUSIONS AND RELEVANCE: This study found reduced incidence of cardiorespiratory hospitalization among those who received HD-IIV vs SD-IIV, driven by a lower incidence of CV hospitalizations, and particularly heart failure hospitalizations. These differences should be interpreted as exploratory findings in the setting of a large RCT with a neutral primary outcome. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05517174.

Aged↗

PubMed2025

Bivalent RSV Prefusion F Protein-Based Vaccine for Preventing Cardiovascular Hospitalizations in Older Adults: A Prespecified Analysis of the DAN-RSV Trial.

IMPORTANCE: Respiratory syncytial virus (RSV) infection is linked to elevated cardiovascular risk, particularly in individuals with preexisting cardiovascular disease (CVD). A bivalent RSV prefusion F protein (RSVpreF) vaccine was recently approved for preventing RSV-related lower respiratory tract illness, but its effectiveness against cardiovascular outcomes has not been evaluated in a randomized trial. OBJECTIVE: To investigate the vaccine effectiveness of RSVpreF compared with no vaccine against cardiovascular outcomes among adults aged 60 years or older. DESIGN, SETTING, AND PARTICIPANTS: Prespecified secondary analysis of the DAN-RSV trial, a pragmatic, open-label, individually randomized clinical trial conducted in Denmark during the 2024-2025 winter season. The first participant was enrolled on November 18, 2024. Adults aged 60 years or older were eligible for inclusion regardless of comorbidity status. INTERVENTIONS: Participants were randomized 1:1 to receive RSVpreF (n = 65 642) or no vaccine (n = 65 634). MAIN OUTCOMES AND MEASURES: Hospitalization for any cardiorespiratory disease was a prespecified secondary outcome, and hospitalizations for any CVD, heart failure, myocardial infarction, stroke, and atrial fibrillation were prespecified exploratory outcomes. Outcomes were assessed from 14 days after booked study visit through May 31, 2025. Vaccine effectiveness was calculated as 1 - incidence rate ratio, expressed as a percentage. RESULTS: Of 131 276 participants included (mean age, 69.4 [SD, 6.5] years; 50.3% male), 28 662 (21.8%) had preexisting CVD. All-cause cardiorespiratory hospitalization incidence was lower in the RSVpreF group compared with the control group (26.3 vs 29.2 events per 1000 participant-years [PY]; absolute rate reduction, 2.90 [95% CI, 0.10-5.71] per 1000 PY; vaccine effectiveness, 9.9% [95% CI, 0.3%-18.7%]; P = .04). There was no significant interaction by baseline CVD status (CVD at baseline: vaccine effectiveness, 5.0% [95% CI, -11.2% to 16.7%]; no CVD at baseline: vaccine effectiveness, 15.2% [95% CI, 2.2%-27.1%]; P = .27 for interaction). For the RSVpreF group vs control group, respectively, incidence rates of all-cause cardiovascular hospitalization were 16.4 vs 17.7 events per 1000 PY (vaccine effectiveness, 7.4% [95% CI, -5.5% to 18.8%]; P = .24), and incidence rates of stroke were 3.0 vs 3.8 events per 1000 PY (vaccine effectiveness, 19.4% [95% CI, -8.6% to 40.4%]; P = .14). There were also no statistically significant between-group differences for myocardial infarction, heart failure hospitalization, and atrial fibrillation. CONCLUSIONS AND RELEVANCE: In adults aged 60 years or older, all-cause cardiorespiratory hospitalization was significantly lower with RSVpreF than with no vaccine. The findings suggest potential downstream cardiorespiratory benefits of RSV immunization, although the effect on all-cause cardiovascular hospitalization was not statistically significant. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT06684743.

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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↗