Anthropometric Measures, Cardiovascular Outcomes, and Treatment Effects of Finerenone in Cardiovascular-Kidney-Metabolic Disease: Pooled Participant-Level Analysis of Three Global Trials.

Background: Obesity is a core pathophysiological contributor to cardiovascular, kidney, and metabolic (CKM) conditions. However, the association between different adiposity-related anthropometrics and cardiovascular outcomes in persons with CKM conditions has not been rigorously explored.

Objectives: To examine cardiovascular outcomes and treatment effects of finerenone according to different adiposity-related anthropometrics.

Serum magnesium and outcomes in heart failure with reduced ejection fraction: the GALACTIC-HF trial.

Background And Aims: The frequency and prognostic significance of abnormalities in serum magnesium concentrations have not been described in a contemporary HF population. The authors evaluated the prognostic significance of magnesium concentrations in patients with HFrEF enrolled in GALACTIC-HF trial.

Methods: GALACTIC-HF was a randomized, double-blind, multicentre, event-driven trial that investigated the efficacy and safety of omecamtiv mecarbil compared to placebo in HF patients with LVEF ≤35%.

Benefit of early initiation of disease-modifying therapy in community-based patients with suspected heart failure.

Background And Aims: The initiation of heart failure (HF) therapies at the time of detection of an elevated N-terminal pro-B-type natriuretic peptide (NT-proBNP) level in community-based patients with suspected HF may reduce the risk of early adverse outcomes. The aim of this analysis was to estimate the potential benefit of the early initiation of a sodium-glucose cotransporter 2 inhibitor (SGLT2i) and/or mineralocorticoid receptor antagonist (MRA) in patients with suspected HF and a preexisting non-HF-related indication for treatment.

Methods: A cohort study was performed from 01/01/2015 to 31/03/2023 using linked primary and secondary care data from the Clinical Practice Research Datalink (CPRD).

Sacubitril/valsartan and Quality of Life Assessed Using the EuroQol 5-Dimension 3-Level Questionnaire Level Sum Score (EQ-5D-3L-LSS) in Patients with HFrEF and HFmrEF/HFpEF.

Objectives: To investigate the EQ-5D-3L Level Sum Score (LSS) in patients with heart failure (HF) and reduced (HFrEF) and mildly reduced or preserved ejection fraction (HFmrEF/HFpEF) and the effect of sacubitril/valsartan on this score using patient-level data from the PARADIGM-HF and PARAGON-HF trials.

Methods: The LSS was calculated by summating the 3 levels (1-3) for each of the 5 domains (minimum sum score=5; maximum sum score=15). Patient characteristics and outcomes were compared across LSS tertiles (T1-T3) at baseline.

Efficacy and Tolerability of Finerenone According to the Use and Dosage of Diuretics: A Prespecified Analysis of the FINEARTS-HF Randomized Clinical Trial.

Importance: Given their kidney actions, it is important to evaluate the efficacy and safety of mineralocorticoid receptor antagonists when combined with other diuretics and whether they have a so-called diuretic-sparing effect in patients with heart failure (HF).

Objective: To examine the efficacy and tolerability of finerenone related to background diuretic treatment in patients with heart failure with mildly reduced or preserved ejection fraction (HFmrEF/HFpEF).

Design, Setting, And Participants: This study is a prespecified secondary analysis of the FINEARTS-HF (Finerenone Trial to Investigate Efficacy and Safety Superior to Placebo in Patients With Heart Failure) randomized clinical trial, which was conducted across 653 sites in 37 countries among adults aged 40 years and older with HFmrEF/HFpEF, who were randomized between September 2020 and January 2023.

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.

Efficacy and Safety of Finerenone in Heart Failure With Preserved Ejection Fraction: A FINE-HEART Analysis.

Background: Pooling data from participants with heart failure with mildly reduced ejection fraction (HFmrEF) or heart failure with preserved ejection fraction (HFpEF) from all completed outcomes trials evaluating finerenone to date may enhance understanding of its safety and efficacy in this high-risk and heterogeneous population.

Objectives: In this prespecified participant-level pooled analysis of the FIDELIO-DKD, FIGARO-DKD, and FINEARTS-HF trials (FINE-HEART), we evaluated the safety and efficacy of finerenone in individuals with HFmrEF/HFpEF.

Methods: The treatment effects of finerenone vs placebo on cardiovascular death or heart failure hospitalization were evaluated using Cox proportional hazards regression models stratified by trial.

Anaemia in patients with heart failure and mildly reduced or preserved ejection fraction: A prespecified analysis of the FINEARTS-HF trial.

Aims: Anaemia is common in heart failure with mildly reduced or preserved ejection fraction (HFmrEF/HFpEF) and associated with poor clinical outcomes. While renin-angiotensin system blockers reduce haemoglobin, little is known about the effect of mineralocorticoid receptor antagonists on haemoglobin and in patients with anaemia. We evaluated the effects of finerenone according to anaemia status in patients with HFmrEF/HFpEF enrolled in FINEARTS-HF.

The efficacy of finerenone on hierarchical composite endpoint analysed using win statistics in patients with heart failure and mildly reduced or preserved ejection fraction: A prespecified analysis of FINEARTS-HF.

Aims: FINEARTS-HF demonstrated the efficacy of finerenone in reducing total worsening heart failure (HF) events (first and recurrent) and cardiovascular death, compared to placebo, in patients with HF and mildly reduced or preserved ejection fraction. We examined the effect of finerenone on these events according to their clinical importance using win statistics.

Methods And Results: We developed a prespecified hierarchical composite endpoint including the components of the original primary outcome: cardiovascular death (tier 1), total HF hospitalizations (tier 2), and total urgent HF visits (tier 3).

Comprehensive Analysis of the Effects of Sacubitril/Valsartan According to Sex Among Patients With Heart Failure and Reduced Ejection Fraction in PARADIGM-HF.

Background: Women with heart failure (HF) ejection fraction appeared to respond more favorably to sacubitril/valsartan, compared with valsartan, than men in PARAGON-HF (Prospective Comparison of ARNI With ARB Global Outcomes in Heart Failure With Preserved Ejection Fraction), driven by a greater reduction in total (first and recurrent) HF hospitalizations. Sex-specific efficacy and safety of sacubitril/valsartan in PARADIGM-HF (Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) remain unreported.

Methods And Results: This post hoc analysis of PARADIGM-HF examined sex-based outcomes in patients with HF and reduced ejection fraction randomized to sacubitril/valsartan or enalapril.

Finerenone, chronic obstructive pulmonary disease, and heart failure with mildly reduced or preserved ejection fraction: A prespecified analysis of the FINEARTS-HF trial.

Aims: Chronic obstructive pulmonary disease (COPD) is associated with worse outcomes in heart failure (HF) with mildly reduced or preserved ejection fraction (HFmrEF/HFpEF). A post hoc analysis of TOPCAT suggested that the effectiveness of the steroidal mineralocorticoid receptor antagonist (MRA), spironolactone, may be modified by pulmonary disease, with a greater benefit in patients with COPD/asthma. We examined the effects of the non-steroidal MRA, finerenone, compared to placebo, according to COPD status in a prespecified analysis of FINEARTS-HF.

Finerenone, glycaemic status, and heart failure with mildly reduced or preserved ejection fraction: A prespecified analysis of the FINEARTS-HF trial.

Aims: The efficacy and safety of the non-steroidal mineralocorticoid receptor antagonist, finerenone, have not been examined in patients without diabetes. We examined the efficacy and safety of finerenone, compared with placebo, according to glycaemic status in FINEARTS-HF.

Methods And Results: A total of 6001 patients with heart failure (HF) with New York Heart Association functional class II-IV, left ventricular ejection fraction ≥40%, evidence of structural heart disease, and elevated N-terminal pro-B-type natriuretic peptide levels were randomized to finerenone or placebo.

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.

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.

Finerenone and new-onset diabetes in heart failure: a prespecified analysis of the FINEARTS-HF trial.

Background: Data on the effect of mineralocorticoid receptor antagonist therapy on HbA levels and new-onset diabetes are conflicting. We aimed to examine the effect of oral finerenone, compared with placebo, on incident diabetes in the Finerenone Trial to Investigate Efficacy and Safety Superior to Placebo in Patients with Heart Failure (FINEARTS-HF) trial.

Methods: In this randomised, double-blind, placebo-controlled trial, 6001 participants with heart failure with New York Heart Association functional class II-IV, left ventricular ejection fraction 40% or higher, evidence of structural heart disease, and elevated N-terminal pro-B-type natriuretic peptide levels were randomly assigned to finerenone or placebo, administered orally.

Initial Decline in Glomerular Filtration Rate With Finerenone in HFmrEF/HFpEF: A Prespecified Analysis of FINEARTS-HF.

Background: An initial decline in estimated glomerular filtration rate (eGFR) often leads to reluctance to continue life-saving therapies in patients with heart failure (HF).

Objectives: The goal of this study was to describe the association between initial decline in eGFR and subsequent clinical outcomes in patients randomized to placebo or finerenone.

Methods: In this prespecified analysis of FINEARTS-HF (Finerenone Trial to Investigate Efficacy and Safety Superior to Placebo in Patients with Heart Failure), we examined the association between initial decline in eGFR (≥15%) from randomization to 1 month and subsequent outcomes in patients assigned to finerenone or placebo.

Finerenone, Obesity, and Heart Failure With Mildly Reduced/Preserved Ejection Fraction: Prespecified Analysis of FINEARTS-HF.

Background: Obesity is associated with excessive adipocyte-derived aldosterone secretion, independent of the classical renin-angiotensin-aldosterone cascade, and mineralocorticoid receptor antagonists may be more effective in patients with heart failure (HF) and obesity.

Objectives: This study sought to examine the effects of the nonsteroidal mineralocorticoid receptor antagonist finerenone compared with placebo, according to body mass index (BMI) in FINEARTS-HF (FINerenone trial to investigate Efficacy and sAfety superioR to placebo in paTientS with Heart Failure).

Methods: A total of 6,001 patients with HF with NYHA functional class II, III, and IV, a left ventricular ejection fraction of ≥40%, evidence of structural heart disease, and elevated natriuretic peptide levels were randomized to finerenone or placebo.

Effects of sacubitril/valsartan according to background beta-blocker therapy in patients with heart failure and reduced ejection fraction: Insights from PARADIGM-HF.

Aims: Beta-blockers may inhibit neprilysin activity and conversely, neprilysin inhibition may have a sympatho-inhibitory action. Consequently, sacubitril/valsartan may have a greater effect in patients not receiving a beta-blocker compared to those treated with a beta-blocker.

Methods And Results: We examined the effect of sacubitril/valsartan compared to enalapril on outcomes according to background beta-blocker treatment in the 8399 patients with heart failure with reduced ejection fraction enrolled in PARADIGM-HF.

Finerenone and Kidney Outcomes in Patients With Heart Failure: The FINEARTS-HF Trial.

Background: Finerenone has kidney-protective effects in patients with chronic kidney disease with type 2 diabetes, but effects on kidney outcomes in patients with heart failure with and without diabetes and/or chronic kidney disease are not known.

Objectives: The purpose of this study was to examine the effects of finerenone on kidney outcomes in FINEARTS-HF (Finerenone Trial to Investigate Efficacy and Safety Superior to Placebo in Patients With Heart Failure), a randomized trial of finerenone vs placebo among patients with heart failure with mildly reduced or preserved ejection fraction.

Methods: We explored the effects of finerenone on the secondary outcome of a sustained ≥50% estimated glomerular filtration rate (eGFR) decline or kidney failure (sustained eGFR decline <15 mL/min/1.

Impacts of the COVID-19 pandemic on deprivation-level differences in cardiovascular hospitalisations: a comparison of England and Denmark using the OpenSAFELY platform and National Registry Data.

Objectives: To examine the impact of the COVID-19 pandemic on deprivation-related inequalities in hospitalisations for cardiovascular disease (CVD) conditions in Denmark and England between March 2018 and December 2021.

Design: Time-series studies in England and Denmark.

Setting: With the approval of National Health Service England, we used English primary care electronic health records, linked to secondary care and death registry data through the OpenSAFELY platform and nationwide Danish health registry data.