Browsing by Author "Lam, Carolyn S. P."

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    Finerenone Reduces New-Onset Atrial Fibrillation in Patients With Chronic Kidney Disease and Type 2 Diabetes
    (Elsevier, 2021) Filippatos, Gerasimos; Bakris, George L.; Pitt, Bertram; Agarwal, Rajiv; Rossing, Peter; Ruilope, Luis M.; Butler, Javed; Lam, Carolyn S. P.; Kolkhof, Peter; Roberts, Luke; Tasto, Christoph; Joseph, Amer; Anker, Stefan D.; FIDELIO-DKD Investigators; Medicine, School of Medicine
    Background: Patients with chronic kidney disease (CKD) and type 2 diabetes (T2D) are at risk of atrial fibrillation or flutter (AFF) due to cardiac remodeling and kidney complications. Finerenone, a novel, selective, nonsteroidal mineralocorticoid receptor antagonist, inhibited cardiac remodeling in preclinical models. Objectives: This work aims to examine the effect of finerenone on new-onset AFF and cardiorenal effects by history of AFF in the Finerenone in Reducing Kidney Failure and Disease Progression in Diabetic Kidney Disease (FIDELIO-DKD) study. Methods: Patients with CKD and T2D were randomized (1:1) to finerenone or placebo. Eligible patients had a urine albumin-to-creatinine ratio ≥30 to ≤5,000 mg/g, an estimated glomerular filtration rate (eGFR) ≥25 to <75 ml/min/1.73 m2 and received optimized doses of renin-angiotensin system blockade. Effect on new-onset AFF was evaluated as a pre-specified outcome adjudicated by an independent cardiologist committee. The primary composite outcome (time to first onset of kidney failure, a sustained decrease of ≥40% in eGFR from baseline, or death from renal causes) and key secondary outcome (time to first onset of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure) were analyzed by history of AFF. Results: Of 5,674 patients, 461 (8.1%) had a history of AFF. New-onset AFF occurred in 82 (3.2%) patients on finerenone and 117 (4.5%) patients on placebo (hazard ratio: 0.71; 95% confidence interval: 0.53-0.94; p = 0.016). The effect of finerenone on primary and key secondary kidney and cardiovascular outcomes was not significantly impacted by baseline AFF (interaction p value: 0.16 and 0.85, respectively). Conclusions: In patients with CKD and T2D, finerenone reduced the risk of new-onset AFF. The risk of kidney or cardiovascular events was reduced irrespective of history of AFF at baseline. (EudraCT 2015-000990-11 [A randomized, double-blind, placebo-controlled, parallel-group, multicenter, event-driven Phase III study to investigate the efficacy and safety of finerenone, in addition to standard of care, on the progression of kidney disease in subjects with type 2 diabetes mellitus and the clinical diagnosis of diabetic kidney disease]; Efficacy and Safety of Finerenone in Subjects With Type 2 Diabetes Mellitus and Diabetic Kidney Disease [FIDELIO-DKD]; NCT02540993).
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    Optimization of Evidence-Based Heart Failure Medications After an Acute Heart Failure Admission: A Secondary Analysis of the STRONG-HF Randomized Clinical Trial
    (American Medical Association, 2024) Cotter, Gad; Deniau, Benjamin; Davison, Beth; Edwards, Christopher; Adamo, Marianna; Arrigo, Mattia; Barros, Marianela; Biegus, Jan; Celutkiene, Jelena; Cerlinskaite-Bajore, Kamile; Chioncel, Ovidiu; Cohen-Solal, Alain; Damasceno, Albertino; Diaz, Rafael; Filippatos, Gerasimos; Gayat, Etienne; Kimmoun, Antoine; Lam, Carolyn S. P.; Metra, Marco; Novosadova, Maria; Pang, Peter S.; Pagnesi, Matteo; Ponikowski, Piotr; Saidu, Hadiza; Sliwa, Karen; Takagi, Koji; Ter Maaten, Jozine M.; Tomasoni, Daniela; Voors, Adriaan; Mebazaa, Alexandre; Emergency Medicine, School of Medicine
    Importance: The Safety, Tolerability, and Efficacy of Rapid Optimization, Helped by N-Terminal Pro-Brain Natriuretic Peptide Testing of Heart Failure Therapies (STRONG-HF) trial strived for rapid uptitration aiming to reach 100% optimal doses of guideline-directed medical therapy (GDMT) within 2 weeks after discharge from an acute heart failure (AHF) admission. Objective: To assess the association between degree of GDMT doses achieved in high-intensity care and outcomes. Design, setting, and participants: This was a post hoc secondary analysis of the STRONG-HF randomized clinical trial, conducted from May 2018 to September 2022. Included in the study were patients with AHF who were not treated with optimal doses of GDMT before and after discharge from an AHF admission. Data were analyzed from January to October 2023. Interventions: The mean percentage of the doses of 3 classes of HF medications (renin-angiotensin system inhibitors, β-blockers, and mineralocorticoid receptor antagonists) relative to their optimal doses was computed. Patients were classified into 3 dose categories: low (<50%), medium (≥50% to <90%), and high (≥90%). Dose and dose group were included as a time-dependent covariate in Cox regression models, which were used to test whether outcomes differed by dose. Main outcome measures: Post hoc secondary analyses of postdischarge 180-day HF readmission or death and 90-day change in quality of life. Results: A total of 515 patients (mean [SD] age, 62.7 [13.4] years; 311 male [60.4%]) assigned high-intensity care were included in this analysis. At 2 weeks, 39 patients (7.6%) achieved low doses, 254 patients (49.3%) achieved medium doses, and 222 patients (43.1%) achieved high doses. Patients with lower blood pressure and more congestion were less likely to be uptitrated to optimal GDMT doses at week 2. As a continuous time-dependent covariate, an increase of 10% in the average percentage optimal dose was associated with a reduction in 180-day HF readmission or all-cause death (primary end point: adjusted hazard ratio [aHR], 0.89; 95% CI, 0.81-0.98; P = .01) and a decrease in 180-day all-cause mortality (aHR, 0.84; 95% CI, 0.73-0.95; P = .007). Quality of life at 90 days, measured by the EQ-5D visual analog scale, improved more in patients treated with higher doses of GDMT (mean difference, 0.10; 95% CI, -4.88 to 5.07 and 3.13; 95% CI, -1.98 to 8.24 points in the medium- and high-dose groups relative to the low-dose group, respectively; P = .07). Adverse events to day 90 occurred less frequently in participants with HIC who were prescribed higher GDMT doses at week 2. Conclusions and relevance: Results of this post hoc analysis of the STRONG-HF randomized clinical trial show that, among patients randomly assigned to high-intensity care, achieving higher doses of HF GDMT 2 weeks after discharge was feasible and safe in most patients.
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    Titration of Medications After Acute Heart Failure Is Safe, Tolerated, and Effective Regardless of Risk
    (Elsevier, 2024-09) Ambrosy, Andrew P.; Chang, Alex J.; Davison, Beth; Voors, Adriaan; Cohen-Solal, Alain; Damasceno, Albertino; Kimmoun, Antoine; Lam, Carolyn S. P.; Edwards, Christopher; Tomasoni, Daniela; Gayat, Etienne; Filippatos, Gerasimos; Saidu, Hadiza; Biegus, Jan; Celutkiene, Jelena; Ter Maaten, Jozine M.; Čerlinskaitė-Bajorė, Kamilė; Sliwa, Karen; Takagi, Koji; Metra, Marco; Novosadova, Maria; Barros, Marianela; Adamo, Marianna; Pagnesi, Matteo; Arrigo, Mattia; Chioncel, Ovidiu; Diaz, Rafael; Pang, Peter S.; Ponikowski, Piotr; Cotter, Gad; Mebazaa , Alexandre; Emergency Medicine, School of Medicine
    Background Guideline-directed medical therapy (GDMT) decisions may be less affected by single patient variables such as blood pressure or kidney function and more by overall risk profile. In STRONG-HF (Safety, tolerability and efficacy of up-titration of guideline-directed medical therapies for acute heart failure), high-intensity care (HIC) in the form of rapid uptitration of heart failure (HF) GDMT was effective overall, but the safety, tolerability and efficacy of HIC across the spectrum of HF severity is unknown. Evaluating this with a simple risk-based framework offers an alternative and more clinically translatable approach than traditional subgroup analyses. Objectives The authors sought to assess safety, tolerability, and efficacy of HIC according to the simple, powerful, and clinically translatable MAGGIC (Meta-Analysis Global Group in Chronic) HF risk score. Methods In STRONG-HF, 1,078 patients with acute HF were randomized to HIC (uptitration of treatments to 100% of recommended doses within 2 weeks of discharge and 4 scheduled outpatient visits over the 2 months after discharge) vs usual care (UC). The primary endpoint was the composite of all-cause death or first HF rehospitalization at day 180. Baseline HF risk profile was determined by the previously validated MAGGIC risk score. Treatment effect was stratified according to MAGGIC risk score both as a categorical and continuous variable. Results Among 1,062 patients (98.5%) with complete data for whom a MAGGIC score could be calculated at baseline, GDMT use at baseline was similar across MAGGIC tertiles. Overall GDMT prescriptions achieved for individual medication classes were higher in the HIC vs UC group and did not differ by MAGGIC risk score tertiles (interaction nonsignificant). The incidence of all-cause death or HF readmission at day 180 was, respectively, 16.3%, 18.9%, and 23.2% for MAGGIC risk score tertiles 1, 2, and 3. The HIC arm was at lower risk of all-cause death or HF readmission at day 180 (HR: 0.66; 95% CI: 0.50-0.86) and this finding was robust across MAGGIC risk score modeled as a categorical (HR: 0.51; 95% CI: 0.62-0.68 in tertiles 1, 2, and 3; interaction nonsignificant) for all comparisons and continuous (interaction nonsignificant) variable. The rate of adverse events was higher in the HIC group, but this observation did not differ based on MAGGIC risk score tertile (interaction nonsignificant). Conclusions HIC led to better use of GDMT and lower HF-related morbidity and mortality compared with UC, regardless of the underlying HF risk profile.