João Pedro Ferreira1,2, Kevin Duarte1, John J V McMurray3, Bertram Pitt4, Dirk J van Veldhuisen5, John Vincent6, Tariq Ahmad7, Jasper Tromp5, Patrick Rossignol1, Faiez Zannad8. 1. Université de Lorraine INSERM, Centre, d'Investigations Cliniques Plurithématique 1433, INSERM U1116, CHRU de Nancy, F-CRIN INI-CRCT, France (J.P.F., K.D., P.R., F.Z.). 2. Department of Physiology and Cardiothoracic Surgery, Cardiovascular Research and Development Unit, Faculty of Medicine, University of Porto, Portugal (J.P.F.). 3. BHF Cardiovascular Research Centre, University of Glasgow, Scotland, United Kingdom (J.J.V.M). 4. Department of Medicine, University of Michigan School of Medicine, Ann Arbor (B.P.). 5. Department of Cardiology, University of Groningen, University Medical Center Groningen, The Netherlands (D.J.v.V., J.T.). 6. Pfizer Inc., New York, NY (J.V.). 7. Section of Cardiovascular Medicine, Yale University School of Medicine, New Haven, CT (T.A.). 8. Université de Lorraine INSERM, Centre, d'Investigations Cliniques Plurithématique 1433, INSERM U1116, CHRU de Nancy, F-CRIN INI-CRCT, France (J.P.F., K.D., P.R., F.Z.). f.zannad@chru-nancy.fr.
Abstract
BACKGROUND:Patients with heart failure with reduced ejection fraction have a poor prognosis. The identification of subgroups with different outcomes and treatment response patterns may help to tailor strategies to each individual patient. We present an exploratory study of patients enrolled in the EMPHASIS-HF trial (Eplerenone in Patients With Systolic Heart Failure and Mild Symptoms) using latent class analysis with validation using the EPHESUS trial (Eplerenone, a Selective Aldosterone Blocker, in Patients With Left Ventricular Dysfunction After Myocardial Infarction) to identify subgroups of patients with different prognosis and response to eplerenone therapy. METHODS AND RESULTS: Latent class analysis identifies mutually exclusive groups of individuals maximizing within-group similarities and between-group differences. In the EMPHASIS-HF trial, 2279 heart failure with reduced ejection fraction patients were randomized to eplerenone or placebo and were characterized according to 18 clinical features. Subgroup definitions were applied to 6472 patients enrolled in the EPHESUS trial to validate observations. Event-free survival and effect of eplerenone on the composite of cardiovascular death and heart failure hospitalization were determined for each subgroup. Four subgroups were identified with significant differences in event-free survival (P=0.002). The subgroup C had the worst event-free survival in both studies and was characterized by older age, lower body mass index, worse renal function, higher baseline potassium levels, high prevalence of anemia, diabetes mellitus, previous revascularization and higher rates of eplerenone discontinuation, and hyperkalemia during follow-up. Two subgroups (B and C) showed a poorer response to eplerenone in both studies and these groups shared common features such as lower body mass index and high prevalence of anemia. Clinical profiles, prognosis, and treatment response patterns of the 4 subgroups applied in EPHESUS trial presented similarities to those observed in EMPHASIS. CONCLUSIONS: Using a data-driven approach, we identified heart failure with reduced ejection fraction subgroups with significantly different prognoses and potentially different responses to eplerenone. However, these data should be regarded as hypothesis-generating and prospective validation is warranted, to assess the potential clinical implications of these subgroups. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00232180.
RCT Entities:
BACKGROUND:Patients with heart failure with reduced ejection fraction have a poor prognosis. The identification of subgroups with different outcomes and treatment response patterns may help to tailor strategies to each individual patient. We present an exploratory study of patients enrolled in the EMPHASIS-HF trial (Eplerenone in Patients With Systolic Heart Failure and Mild Symptoms) using latent class analysis with validation using the EPHESUS trial (Eplerenone, a Selective Aldosterone Blocker, in Patients With Left Ventricular Dysfunction After Myocardial Infarction) to identify subgroups of patients with different prognosis and response to eplerenone therapy. METHODS AND RESULTS: Latent class analysis identifies mutually exclusive groups of individuals maximizing within-group similarities and between-group differences. In the EMPHASIS-HF trial, 2279 heart failure with reduced ejection fraction patients were randomized to eplerenone or placebo and were characterized according to 18 clinical features. Subgroup definitions were applied to 6472 patients enrolled in the EPHESUS trial to validate observations. Event-free survival and effect of eplerenone on the composite of cardiovascular death and heart failure hospitalization were determined for each subgroup. Four subgroups were identified with significant differences in event-free survival (P=0.002). The subgroup C had the worst event-free survival in both studies and was characterized by older age, lower body mass index, worse renal function, higher baseline potassium levels, high prevalence of anemia, diabetes mellitus, previous revascularization and higher rates of eplerenone discontinuation, and hyperkalemia during follow-up. Two subgroups (B and C) showed a poorer response to eplerenone in both studies and these groups shared common features such as lower body mass index and high prevalence of anemia. Clinical profiles, prognosis, and treatment response patterns of the 4 subgroups applied in EPHESUS trial presented similarities to those observed in EMPHASIS. CONCLUSIONS: Using a data-driven approach, we identified heart failure with reduced ejection fraction subgroups with significantly different prognoses and potentially different responses to eplerenone. However, these data should be regarded as hypothesis-generating and prospective validation is warranted, to assess the potential clinical implications of these subgroups. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00232180.
Authors: Jordana B Cohen; Sarah J Schrauben; Lei Zhao; Michael D Basso; Mary Ellen Cvijic; Zhuyin Li; Melissa Yarde; Zhaoqing Wang; Priyanka T Bhattacharya; Diana A Chirinos; Stuart Prenner; Payman Zamani; Dietmar A Seiffert; Bruce D Car; David A Gordon; Kenneth Margulies; Thomas Cappola; Julio A Chirinos Journal: JACC Heart Fail Date: 2020-01-08 Impact factor: 12.035
Authors: Szymon Urban; Mikołaj Błaziak; Maksym Jura; Gracjan Iwanek; Agata Zdanowicz; Mateusz Guzik; Artur Borkowski; Piotr Gajewski; Jan Biegus; Agnieszka Siennicka; Maciej Pondel; Petr Berka; Piotr Ponikowski; Robert Zymliński Journal: Biomedicines Date: 2022-06-27