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14 results on '"MESH: Mineralocorticoid Receptor Antagonists"'

1. Effect of eplerenone in percutaneous coronary intervention-treated post-myocardial infarction patients with left ventricular systolic dysfunction: a subanalysis of the EPHESUS trial

Author

Julian Gunn, Iain B. Squire, David Adlam, Renaud Fay, Yasir Parviz, Faiez Zannad, Bertram Pitt, Javaid Iqbal, University of Sheffield [Sheffield], Sheffield Teaching Hospitals, Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Cardiologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Glenfield Hospital, University of Michigan [Ann Arbor], University of Michigan System, Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM), Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), and Université de Lorraine (UL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)

Subjects
Male, medicine.medical_treatment, MESH: Comorbidity, Comorbidity, Spironolactone, 030204 cardiovascular system & hematology, Angina, Ventricular Dysfunction, Left, MESH: Aged, 80 and over, 0302 clinical medicine, MESH: Ventricular Dysfunction, Left, MESH: Double-Blind Method, 030212 general & internal medicine, Myocardial infarction, Mineralocorticoid Receptor Antagonists, MESH: Treatment Outcome, Aged, 80 and over, MESH: Aged, MESH: Middle Aged, Standard treatment, Middle Aged, 3. Good health, Eplerenone, MESH: Myocardial Infarction, Treatment Outcome, surgical procedures, operative, MESH: Spironolactone, Cohort, Cardiology, Female, Cardiology and Cardiovascular Medicine, MESH: Percutaneous Coronary Intervention, therapeutics, medicine.drug, medicine.medical_specialty, Heart failure, MESH: Mineralocorticoid Receptor Antagonists, 03 medical and health sciences, Percutaneous Coronary Intervention, Double-Blind Method, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Internal medicine, medicine, Humans, cardiovascular diseases, Aged, MESH: Humans, business.industry, Angioplasty, Percutaneous coronary intervention, medicine.disease, MESH: Male, Clinical trial, Conventional PCI, business, MESH: Female
Abstract

Aims EPHESUS was a multicentre, double-blind clinical trial in which 6632 patients with acute myocardial infarction (AMI) complicated by LV systolic dysfunction (LVSD) were randomized to receive eplerenone (n = 3319) or placebo (n = 3313). A total of 1580 EPHESUS patients were treated with PCI, which is now the standard treatment for AMI. This EPHESUS substudy examined the effects of eplerenone upon cardiovascular outcomes in PCI-treated patients. Methods and results EPHESUS patients were divided into PCI-treated and non-PCI-treated cohorts, and the effect of eplerenone upon mortality and other major adverse cardiovascular outcomes was assessed in each cohort. The PCI-treated patients (n = 1580) were younger, and had better renal function and fewer co-morbidities than non-PCI-treated patients (n = 5052). Cardiovascular mortality was significantly lower in PCI-treated patients as compared with non-PCI-treated patients (7% vs. 16%, P < 0.0001). However, the incidence of non-fatal events was similar in PCI-treated and non-PCI-treated cohorts. There was no statistical difference between the PCI-treated and non-PCI-treated cohorts in the primary or secondary outcomes of the trial. Eplerenone administration, compared with placebo, in the PCI-treated cohort did not affect PCI-related clinical outcomes, including recurrence of angina, the occurrence of acute coronary syndromes, or the need for further revascularization. Conclusions The beneficial effects of eplerenone in the EPHESUS trial exist for both PCI- and non-PCI-treated AMI patients with LVSD. Eplerenone has minimal, if any, effect upon reducing PCI-related adverse events in the PCI-treated cohort.

Published
2014
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2. Heart failure with systolic dysfunction complicating acute myocardial infarction – differential outcomes but similar eplerenone efficacy by ST-segment or non-ST-segment elevation: A post hoc substudy of the EPHESUS trial

Author

Bertram Pitt, Santosh C. Sutradhor, Michael Angioi, Sylvain Carillo, John Vincent, Renaud Fay, Ali Ahmed, Yan Zhang, Faiez Zannad, Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Alabama at Birmingham [ Birmingham] (UAB), Birmingham VA Medical Center, University of Alabama [Tuscaloosa] (UA), Clinique Louis-Pasteur, Pfizer, University of California [Davis] (UC Davis), University of California, University of Michigan [Ann Arbor], University of Michigan System, Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), and Université de Lorraine (UL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)

Subjects
MESH: Coronary Thrombosis, Male, medicine.medical_treatment, Myocardial Infarction, MESH: Comorbidity, MESH: Myocardial Revascularization, Comorbidity, Spironolactone, MESH: Proportional Hazards Models, MESH: Cause of Death, Electrocardiography, Mineralocorticoid receptor, Cause of Death, Myocardial Revascularization, ST segment, Multicenter Studies as Topic, Myocardial infarction, MESH: Treatment Outcome, Mineralocorticoid Receptor Antagonists, Randomized Controlled Trials as Topic, MESH: Aged, MESH: Middle Aged, Ejection fraction, General Medicine, Middle Aged, Prognosis, 3. Good health, Eplerenone, MESH: Myocardial Infarction, Treatment Outcome, Cardiovascular Diseases, MESH: Spironolactone, Cardiology, Disease Progression, MESH: Disease Progression, Female, MESH: Cardiovascular Agents, IDM ST+, Cardiology and Cardiovascular Medicine, medicine.drug, medicine.medical_specialty, Post hoc, MESH: Mineralocorticoid Receptor Antagonists, Éplérénone, Revascularization, MESH: Prognosis, STEMI, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, IDM ST–, Internal medicine, medicine, Humans, cardiovascular diseases, Aged, Proportional Hazards Models, Retrospective Studies, Heart Failure, MESH: Humans, business.industry, Coronary Thrombosis, MESH: Cardiovascular Diseases, MESH: Retrospective Studies, Cardiovascular Agents, medicine.disease, MESH: Male, MESH: Electrocardiography, Insuffisance cardiaque, NSTEMI, MESH: Randomized Controlled Trials as Topic, Heart failure, MESH: Heart Failure, MESH: Multicenter Studies as Topic, business, MESH: Female
Abstract

International audience; BACKGROUND:Differential outcomes in patients with acute systolic heart failure (HF) complicating acute myocardial infarction (AMI) and the efficacy of mineralocorticoid receptor antagonists according to non-ST-segment and ST-segment elevation myocardial infarction (NSTEMI, STEMI) status has not been specifically investigated.METHODS:In the EPHESUS study, 6632 patients with acute HF and left ventricular ejection fraction

Published
2014
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3. Galectin-3 Mediates Aldosterone-Induced Vascular Fibrosis

Author

Patrick Lacolley, Françoise Poirier, Faiez Zannad, Victoria Cachofeiro, Ernesto Martínez-Martínez, Rudolf A. de Boer, Natalia López-Andrés, María Miana, Pascal Reboul, Laurent Calvier, Patrick Rossignol, Risque cardiovasculaire, rigidité-fibrose et hypercoagulabilité (RCV), Université Henri Poincaré - Nancy 1 (UHP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Universidad Complutense de Madrid [Madrid] (UCM), Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Department of Cardiology [UMCG], University Medical Center Groningen [Groningen] (UMCG), Institut Jacques Monod (IJM (UMR_7592)), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre d'Investigation Clinique - Epidemiologie Clinique/essais Cliniques Nancy, Cancéropôle du Grand Est-Institut National de la Santé et de la Recherche Médicale (INSERM), Universidad Complutense de Madrid = Complutense University of Madrid [Madrid] (UCM), and Cardiovascular Centre (CVC)

Subjects
Male, MESH: Inflammation, CARDIOTROPHIN-1, Time Factors, Vascular smooth muscle, Galectin 3, SMOOTH-MUSCLE-CELLS, MESH: Collagen Type I, Blood Pressure, 030204 cardiovascular system & hematology, MESH: Mice, Knockout, Muscle, Smooth, Vascular, MESH: Vascular Stiffness, MESH: Hypertension, Muscle hypertrophy, chemistry.chemical_compound, 0302 clinical medicine, Fibrosis, MESH: Up-Regulation, vascular smooth muscle cells, Myocyte, MESH: Animals, Cells, Cultured, Mineralocorticoid Receptor Antagonists, Mice, Knockout, 0303 health sciences, Aldosterone, MESH: Myocytes, Smooth Muscle, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, MESH: Muscle, Smooth, Vascular, MESH: Blood Pressure, Up-Regulation, 3. Good health, INSIGHTS, Galectin-3, Hypertension, MESH: Fibrosis, HEART-FAILURE, RNA Interference, medicine.symptom, Cardiology and Cardiovascular Medicine, MESH: Cells, Cultured, EXPRESSION, endocrine system, medicine.medical_specialty, MESH: Rats, Cardiotrophin 1, Myocytes, Smooth Muscle, MESH: RNA Interference, collagen type I, Inflammation, MESH: Mineralocorticoid Receptor Antagonists, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, Transfection, 03 medical and health sciences, Vascular Stiffness, LEFT-VENTRICULAR DYSFUNCTION, INFLAMMATION, MESH: Mice, Inbred C57BL, Internal medicine, galectin-3, EXTRACELLULAR-MATRIX, medicine, Animals, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Rats, Wistar, MESH: Mice, 030304 developmental biology, MESH: Humans, aldosterone, MESH: Transfection, MESH: Time Factors, fibrosis, MESH: Aldosterone, MESH: Rats, Wistar, medicine.disease, ENDOTHELIAL-CELLS, MESH: Male, MESH: Galectin 3, Rats, Mice, Inbred C57BL, Disease Models, Animal, MICE, Endocrinology, chemistry, MESH: Disease Models, Animal
Abstract

Objective— Aldosterone (Aldo) is involved in arterial stiffness and heart failure, but the mechanisms have remained unclear. Galectin-3 (Gal-3), a β-galactoside-binding lectin, plays an important role in inflammation, fibrosis, and heart failure. We investigated here whether Gal-3 is involved in Aldo-induced vascular fibrosis. Methods and Results— In rat vascular smooth muscle cells Gal-3 overexpression enhanced specifically collagen type I synthesis. Moreover Gal-3 inhibition by modified citrus pectin or small interfering RNA blocked Aldo-induced collagen type I synthesis. Rats were treated with Aldo-salt combined with spironolactone or modified citrus pectin for 3 weeks. Hypertensive Aldo-treated rats presented vascular hypertrophy, inflammation, fibrosis, and increased aortic Gal-3 expression. Spironolactone or modified citrus pectin treatment reversed all the above effects. Wild-type and Gal-3 knock-out mice were treated with Aldo for 6 hours or 3 weeks. Aldo increased aortic Gal-3 expression, inflammation, and collagen type I in wild-type mice at both the short- and the long-term, whereas no changes occurred in Gal-3 knock-out mice. Conclusion— Our data indicate that Gal-3 is required for inflammatory and fibrotic responses to Aldo in vascular smooth muscle cells in vitro and in vivo, suggesting a key role for Gal-3 in vascular fibrosis.

Published
2013
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4. The safety of mineralocorticoid receptor antagonists (MRAs) in patients with heart failure

Author

Patrick Rossignol, Bertram Pitt, University of Michigan [Ann Arbor], University of Michigan System, Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), CIC-Nancy, Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'investigation clinique [Nancy] (CIC), and Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
medicine.medical_specialty, Hyperkalemia, Renal function, MESH: Hospitalization, MESH: Mineralocorticoid Receptor Antagonists, 030204 cardiovascular system & hematology, 03 medical and health sciences, Ventricular Dysfunction, Left, 0302 clinical medicine, Mineralocorticoid receptor, MESH: Practice Guidelines as Topic, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Internal medicine, MESH: Ventricular Dysfunction, Left, Medicine, Humans, MESH: Patient Selection, Pharmacology (medical), mineralocorticoid receptor antagonist, 030212 general & internal medicine, Dosing, ComputingMilieux_MISCELLANEOUS, Mineralocorticoid Receptor Antagonists, Heart Failure, MESH: Kidney Diseases, MESH: Humans, Ejection fraction, business.industry, Patient Selection, renal function, General Medicine, medicine.disease, 3. Good health, Hospitalization, Heart failure, MESH: Heart Failure, Inclusion and exclusion criteria, Practice Guidelines as Topic, Cardiology, MESH: Hyperkalemia, Kidney Diseases, medicine.symptom, business, MRAS
Abstract

Mineralocorticoid receptor antagonists (MRAs) have been accorded a class 1 indication for patients with chronic heart failure and a reduced left ventricular ejection fraction (HFREF) in both European and American guidelines. Uptake, however, has been less than optimal largely due to concerns about their safety, in particular the risk of hyperkalemia and renal dysfunction.This review presents the current state of affairs regarding the safety of MRAs in heart failure with reduced ejection fraction.Careful patient selection and adherence to guideline-recommended inclusion and exclusion criteria, dosing, and serial monitoring of serum potassium and renal function, along with patient education regarding the potassium content of common foods, should minimize these risks and allow increased use of MRAs. Additionally, this may also result in a further reduction in cardiovascular mortality and hospitalizations for heart failure. The development of new non-steroidal MRAs, and especially new potassium binding molecules that are well tolerated and effective, hold the promise for increased safety and, therefore, increased and more prolonged use of MRAs in patients with heart failure, especially those with chronic kidney disease, diabetes mellitus, and the elderly.

Published
2016
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5. Galectin-3 Blockade Inhibits Cardiac Inflammation and Fibrosis in Experimental Hyperaldosteronism and HypertensionNovelty and Significance

Author

Martinez-Martinez, Ernesto, Calvier, Laurent, Fernández-Celis, Amaya, Rousseau, Elodie, Jurado-López, Raquel, Rossoni, Luciana, Jaisser, Frederic, Zannad, Faiez, Rossignol, Patrick, Cachofeiro, Victoria, López-Andrés, Natalia, Fundación Miguel Servet, Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Instituto de Investigación Sanitaria Gregorio Marañón [Madrid, Spain] ( IiSGM), Universidade de Sao Paulo, Institute of Biomedical Sciences, Universidade de São Paulo (USP)-Institute of Biomedical Sciences (ICB/USP), Universidade de São Paulo (USP), Centre de Recherche des Cordeliers (CRC), Université Pierre et Marie Curie - Paris 6 (UPMC)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), CIC-Nancy, Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy]-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Lorraine (UL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Universidade de São Paulo = University of São Paulo (USP)-Institute of Biomedical Sciences (ICB/USP), Universidade de São Paulo = University of São Paulo (USP), and Université Pierre et Marie Curie - Paris 6 (UPMC)-École Pratique des Hautes Études (EPHE)

Subjects
aldosterone, hypertension, MESH: Humans, MESH: Rats, fibrosis, MESH: Mineralocorticoid Receptor Antagonists, MESH: Rats, Wistar, galectin 3, MESH: Mice, Knockout, MESH: Galectin 3, MESH: Hypertension, MESH: Male, MESH: Hyperaldosteronism, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, inflammation, MESH: Mice, Inbred C57BL, MESH: Myocarditis, MESH: Fibroblasts, MESH: Spironolactone, MESH: Fibrosis, MESH: Animals, MESH: Disease Models, Animal, MESH: Mice, MESH: Rats, Inbred WKY, MESH: Cells, Cultured
Abstract

International audience; Hypertensive cardiac remodeling is accompanied by molecular inflammation and fibrosis, 2 mechanisms that finally affect cardiac function. At cardiac level, aldosterone promotes inflammation and fibrosis, although the precise mechanisms are still unclear. Galectin-3 (Gal-3), a β-galactoside-binding lectin, is associated with inflammation and fibrosis in the cardiovascular system. We herein investigated whether Gal-3 inhibition could block aldosterone-induced cardiac inflammation and fibrosis and its potential role in cardiac damage associated with hypertension. Aldosterone-salt-treated rats presented hypertension, cardiac inflammation, and fibrosis that were prevented by the pharmacological inhibition of Gal-3 with modified citrus pectin. Cardiac inflammation and fibrosis presented in spontaneously hypertensive rats were prevented by modified citrus pectin treatment, whereas Gal-3 blockade did not modify blood pressure levels. In the absence of blood pressure modifications, Gal-3 knockout mice were resistant to aldosterone-induced cardiac inflammation. In human cardiac fibroblasts, aldosterone increased Gal-3 expression via its mineralocorticoid receptor. Gal-3 and aldosterone enhanced proinflammatory and profibrotic markers, as well as metalloproteinase activities in human cardiac fibroblasts, effects that were not observed in Gal-3-silenced cells treated with aldosterone. In experimental hyperaldosteronism, the increase in Gal-3 expression was associated with cardiac inflammation and fibrosis, alterations that were prevented by Gal-3 blockade independently of blood pressure levels. These data suggest that Gal-3 could be a new molecular mechanism linking cardiac inflammation and fibrosis in situations with high-aldosterone levels, such as hypertension.

Published
2015
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6. Clinical benefits of eplerenone in patients with systolic heart failure and mild symptoms when initiated shortly after hospital discharge: analysis from the EMPHASIS-HF trial

Author

Timothy Collier, Nicolas Girerd, Stuart J. Pocock, John J.V. McMurray, John Vincent, Henry Krum, Bertram Pitt, Karl Swedberg, Faiez Zannad, Dirk J. van Veldhuisen, Cardiovascular Centre (CVC), Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM), Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Université de Lorraine (UL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), London School of Hygiene and Tropical Medicine (LSHTM), Center of Cardiovascular Research and Education in Therapeutics [Monash University - Melbourne], Monash University [Melbourne], British Heart Foundation Glasgow Cardiovascular Research Centre (BHF GCRC), University of Glasgow-NHS Greater Glasgow and Clyde, National Heart and Lung Institute [London, UK], Imperial College London-British Heart Foundation, Department of molecular and clinical medicine [Gothenburg], University of Gothenburg (GU), University Medical Center Groningen [Groningen] (UMCG), Pfizer, University of Michigan [Ann Arbor], and University of Michigan System

Subjects
Male, IMPACT, MESH: Hospitalization, 030204 cardiovascular system & hematology, Spironolactone, GUIDELINES, THERAPY, HYPERKALEMIA, chemistry.chemical_compound, 0302 clinical medicine, Secondary Prevention, 030212 general & internal medicine, PREDICTORS, MESH: Treatment Outcome, Mineralocorticoid Receptor Antagonists, MESH: Aged, Ejection fraction, MESH: Middle Aged, MESH: Secondary Prevention, MESH: Heart Failure, Systolic, MESH: Follow-Up Studies, ASSOCIATION, Middle Aged, 3. Good health, Eplerenone, Hospitalization, Treatment Outcome, MESH: Spironolactone, ALDOSTERONE ANTAGONISTS, Cardiology, MESH: Hyperkalemia, Female, Cardiology and Cardiovascular Medicine, medicine.drug, medicine.medical_specialty, Acute coronary syndrome, MESH: Mineralocorticoid Receptor Antagonists, Placebo, Patient Readmission, 03 medical and health sciences, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Internal medicine, medicine, MESH: Patient Readmission, Humans, Timing, Acute Coronary Syndrome, Adverse effect, Survival analysis, Aged, MESH: Humans, business.industry, MORTALITY, Treatment effect, medicine.disease, MESH: Acute Coronary Syndrome, EMPHASIS-HF, MESH: Male, chemistry, PERSPECTIVES, Heart failure, business, INHIBITORS, MESH: Female, Follow-Up Studies, Heart Failure, Systolic, Systolic heart failure
Abstract

International audience; AIMS:Cardiovascular hospitalization (CVH) in patients with heart failure (HF) is associated with a high post-discharge rate of early re-admission and CV death. Eplerenone might be effective in reducing the incidence of these adverse clinical outcomes during this period.METHODS AND RESULTS:The EMPHASIS-HF trial compared eplerenone with placebo added to standard therapy in 2737 patients with New York Heart Association class II HF and left ventricular ejection fraction ≤35%. We conducted a post hoc analysis in the 2338 patients randomized within 180 days of a CVH. The interaction between the time from the qualifying CVH to randomization and the primary outcome of CV death or hospitalization for HF (HHF), as well as other secondary outcomes, was assessed in Cox survival models. Most of the qualifying CVHs were HHF (N = 1496, 64.0%), acute coronary syndromes (N = 390, 16.7%), and arrhythmias (N = 197, 7.2%). The median time of study drug initiation from qualifying CVH was 42 days. The relative rate reductions in CV death/HHF, HHF, and all-cause mortality were similar (P for interaction = 0.65, 0.44, and 0.40, respectively) whether the treatment was initiated

Published
2015
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7. Rationale and design of MinerAlocorticoid Receptor antagonist Tolerability Study-Heart Failure (ARTS-HF): a randomized study of finerenone vs. eplerenone in patients who have worsening chronic heart failure with diabetes and/or chronic kidney disease

Author

So Young Kim, Piotr Ponikowski, Stefan D. Anker, Henry Krum, Michael Böhm, Lars Køber, Christina Nowack, Mihai Gheorghiade, Bertram Pitt, Gerasimos Filippatos, Adriaan A. Voors, Aldo P. Maggioni, Faiez Zannad, Nina Kimmeskamp-Kirschbaum, Alexander Pieper, University of Michigan [Ann Arbor], University of Michigan System, University Medical Center Göttingen (UMG), Universitätsklinikum des Saarlandes, Center for Cardiovascular Innovation, Feinberg School of Medicine, Northwestern University [Evanston]-Northwestern University [Evanston], Rigshospitalet [Copenhagen], Copenhagen University Hospital, Center of Cardiovascular Research and Education in Therapeutics [Monash University - Melbourne], Monash University [Melbourne], Research Center [Associazione Nazionale Medici Cardiologi Ospedalieri] (ANMCO Research Center), Associazione Nazionale Medici Cardiologi Ospedalieri [Firenze] (ANMCO), Wroclaw Medical University, University Medical Center Groningen [Groningen] (UMCG), Service de Cardiologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Global Clinical Development, Bayer HealthCare AG, M.A.R.C.O. GmbH & Co, University General Hospital ' Attikon ' [Athens, Greece], and Cardiovascular Centre (CVC)

Subjects
EUROBSERVATIONAL RESEARCH-PROGRAM, Mineralocorticoid receptor, MESH: Comorbidity, Comorbidity, BAY 94-8862, 030204 cardiovascular system & hematology, chemistry.chemical_compound, DOUBLE-BLIND, 0302 clinical medicine, Chronic kidney disease, Natriuretic Peptide, Brain, MESH: Double-Blind Method, 030212 general & internal medicine, MESH: Natriuretic Peptide, Brain, MESH: Peptide Fragments, Mineralocorticoid Receptor Antagonists, education.field_of_study, MESH: Naphthyridines, SPIRONOLACTONE, 3. Good health, Eplerenone, Tolerability, BRAIN NATRIURETIC PEPTIDE, ALDOSTERONE ANTAGONISTS, MESH: Spironolactone, Cardiology, TRIAL, Natriuretic Agents, Cardiology and Cardiovascular Medicine, medicine.drug, MESH: Diabetes Mellitus, Type 2, medicine.medical_specialty, Finerenone, Population, MESH: Renal Insufficiency, Chronic, Heart failure, MESH: Mineralocorticoid Receptor Antagonists, 03 medical and health sciences, Double-Blind Method, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Internal medicine, Diabetes mellitus, Type 2 diabetes mellitus, medicine, Humans, Naphthyridines, Renal Insufficiency, Chronic, Intensive care medicine, education, HOSPITAL DISCHARGE, MESH: Humans, business.industry, Antagonist, medicine.disease, Peptide Fragments, chemistry, Diabetes Mellitus, Type 2, MESH: Heart Failure, MESH: Natriuretic Agents, Spironolactone, business, FOLLOW-UP, Kidney disease, TASK-FORCE
Abstract

International audience; AIMS:To investigate the safety and potential efficacy of the novel non-steroidal mineralocorticoid receptor antagonist finerenone in patients with worsening chronic heart failure and reduced left ventricular ejection fraction (HFrEF) and at high risk of hyperkalaemia and worsening renal dysfunction.METHODS AND RESULTS:The MinerAlocorticoid Receptor antagonist Tolerability Study-Heart Failure (ARTS-HF; NCT01807221) is a multicentre, randomized, double-blind, active-comparator-controlled, six-parallel-group, phase 2b dose-finding study. In total, 1060 patients with HFrEF and concomitant type 2 diabetes mellitus and/or chronic kidney disease (CKD) will be randomized within 7 days of emergency presentation to hospital for worsening chronic HF to receive finerenone (one of five doses in the range 2.5-20.0 mg once daily) or eplerenone (25 mg every second day to 50 mg once daily for 90 days). The primary objective is to investigate the safety and potential efficacy (measured as the percentage of individuals with a decrease in plasma N-terminal pro-B-type natriuretic peptide [NT-proBNP] of more than 30% relative to baseline at day 90 ± 2) of different oral doses of finerenone compared with eplerenone. Other objectives are to assess the effects of finerenone on a composite clinical endpoint (death from any cause, cardiovascular hospitalizations, or emergency presentations for worsening chronic HF), and on changes in health-related quality of life from baseline.CONCLUSIONS:ARTS-HF is the first phase 2b clinical trial to investigate the effects of finerenone on plasma NT-proBNP in a high-risk population of patients who have worsening chronic HF with type 2 diabetes mellitus and/or CKD presenting at the emergency department.

Published
2015
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8. Clinical outcomes according to QRS duration and morphology in the Eplerenone in Mild Patients: Hospitalization and Survival Study in Heart Failure (EMPHASIS-HF)

Author

Jane A, Cannon, Timothy J, Collier, Li, Shen, Karl, Swedberg, Henry, Krum, Dirk J, Van Veldhuisen, John, Vincent, Stuart J, Pocock, Bertram, Pitt, Faiez, Zannad, John J V, McMurray, Cardiovascular Centre (CVC), BHF Glasgow Cardiovascular Research Centre, University of Glasgow, London School of Hygiene and Tropical Medicine (LSHTM), University of Gothenburg (GU), Monash University [Melbourne], University Medical Center Groningen [Groningen] (UMCG), Pfizer Pharma GmbH, Pfizer, University of Michigan [Ann Arbor], University of Michigan System, Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre d'investigation clinique [Nancy] (CIC), and Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Male, MESH: Survival Rate, IMPACT, MESH: Random Allocation, CARDIAC-RESYNCHRONIZATION-THERAPY, MESH: Hospitalization, MESH: Mineralocorticoid Receptor Antagonists, Spironolactone, GUIDELINES, MESH: Stroke Volume, Electrocardiography, Random Allocation, MORBIDITY, Double-Blind Method, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Humans, MESH: Double-Blind Method, BENEFIT, cardiovascular diseases, eplerenone, METAANALYSIS, Aged, Mineralocorticoid Receptor Antagonists, MESH: Treatment Outcome, Heart Failure, MESH: Aged, MESH: Humans, MESH: Middle Aged, MORTALITY, systolic heart failure, Stroke Volume, clinical trial, Middle Aged, MESH: Male, MESH: Electrocardiography, PREVALENCE, Hospitalization, Survival Rate, Treatment Outcome, MESH: Spironolactone, MESH: Heart Failure, cardiovascular system, Female, MESH: Female, BUNDLE-BRANCH BLOCK, TASK-FORCE, circulatory and respiratory physiology
Abstract

International audience; AIMS:We examined the relationship between different degrees of QRS prolongation and different QRS morphologies and clinical outcomes in patients with heart failure, reduced ejection fraction (HF-REF), and mild symptoms in the Eplerenone in Mild Patients Hospitalization and SurvIval Study in Heart Failure trial (EMPHASIS-HF). We also evaluated the effect of eplerenone in these patients according to QRS duration/morphology.METHODS AND RESULTS:Patients were categorized as: QRS duration (ms) (i)

Published
2015
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9. The Impact of Galectin-3 Inhibition on Aldosterone-Induced Cardiac and Renal Injuries

Author

Laurent Calvier, Natalia López-Andrés, J. Rafael Sadaba, Elodie Rousseau, María Miana, Patrick Rossignol, Faiez Zannad, Ernesto Martínez-Martínez, Victoria Cachofeiro, Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Université de Lorraine (UL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Fundación Miguel Servet, Universidad Complutense de Madrid = Complutense University of Madrid [Madrid] (UCM), Complejo Hospitalario de Navarra, Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), and Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy]

Subjects
Male, collagen, Renal Hypertrophy, Galectin 3, 030204 cardiovascular system & hematology, Spironolactone, MESH: Mice, Knockout, chemistry.chemical_compound, Mice, 0302 clinical medicine, Mineralocorticoid receptor, Fibrosis, MESH: Animals, Mineralocorticoid Receptor Antagonists, Mice, Knockout, 0303 health sciences, Aldosterone, MESH: Enzyme-Linked Immunosorbent Assay, cardiorenal injury, Acute Kidney Injury, Hyperaldosteronism, Immunohistochemistry, 3. Good health, Galectin-3, MESH: Spironolactone, biomarker, Cardiology and Cardiovascular Medicine, medicine.medical_specialty, MESH: Rats, MESH: Acute Kidney Injury, Enzyme-Linked Immunosorbent Assay, MESH: Mineralocorticoid Receptor Antagonists, 03 medical and health sciences, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, MESH: Mice, Inbred C57BL, Internal medicine, galectin-3, medicine, Renal fibrosis, Animals, Rats, Wistar, MESH: Mice, 030304 developmental biology, Heart Failure, aldosterone, business.industry, MESH: Aldosterone, MESH: Immunohistochemistry, MESH: Rats, Wistar, medicine.disease, MESH: Galectin 3, MESH: Male, Rats, Mice, Inbred C57BL, Disease Models, Animal, Endocrinology, chemistry, MESH: Heart Failure, MESH: Disease Models, Animal, business
Abstract

Objectives This study investigated whether galectin (Gal)-3 inhibition could block aldosterone-induced cardiac and renal fibrosis and improve cardiorenal dysfunction. Background Aldosterone is involved in cardiac and renal fibrosis that is associated with the development of cardiorenal injury. However, the mechanisms of these interactions remain unclear. Gal-3, a β-galactoside–binding lectin, is increased in heart failure and kidney injury. Methods Rats were treated with aldosterone-salt combined with spironolactone (a mineralocorticoid receptor antagonist) or modified citrus pectin (a Gal-3 inhibitor), for 3 weeks. Wild-type and Gal-3 knockout mice were treated with aldosterone for 3 weeks. Hemodynamic, cardiac, and renal parameters were analyzed. Results Hypertensive aldosterone-salt–treated rats presented cardiac and renal hypertrophy (at morphometric, cellular, and molecular levels) and dysfunction. Cardiac and renal expressions of Gal-3 as well as levels of molecular markers attesting fibrosis were also augmented by aldosterone-salt treatment. Spironolactone or modified citrus pectin treatment reversed all of these effects. In wild-type mice, aldosterone did not alter blood pressure levels but increased cardiac and renal Gal-3 expression, fibrosis, and renal epithelial-mesenchymal transition. Gal-3 knockout mice were resistant to aldosterone effects. Conclusions In experimental hyperaldosteronism, the increase in Gal-3 expression was associated with cardiac and renal fibrosis and dysfunction but was prevented by pharmacological inhibition (modified citrus pectin) or genetic disruption of Gal-3. These data suggest a key role for Gal-3 in cardiorenal remodeling and dysfunction induced by aldosterone. Gal-3 could be used as a new biotarget for specific pharmacological interventions.

Published
2015
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10. Time to retrieve the best benefits from renin angiotensin aldosterone system (RAAS) inhibition in heart failure patients with reduced ejection fraction: Lessons from randomized controlled trials and registries

Author

Faiez Zannad, Bertram Pitt, Patrick Rossignol, Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM), Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Université de Lorraine (UL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service de Cardiologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), University of Michigan [Ann Arbor], and University of Michigan System

Subjects
Time Factors, Hyperkalemia, MESH: Registries, Tetrazoles, MESH: Aminobutyrates, 030204 cardiovascular system & hematology, MESH: Stroke Volume, law.invention, Renin-Angiotensin System, 0302 clinical medicine, Mineralocorticoid receptor, Randomized controlled trial, law, MESH: Renin-Angiotensin System, 030212 general & internal medicine, Registries, health care economics and organizations, Mineralocorticoid Receptor Antagonists, Randomized Controlled Trials as Topic, Ejection fraction, Aminobutyrates, 3. Good health, Drug Combinations, MESH: Angiotensin Receptor Antagonists, Cardiology, Valsartan, medicine.symptom, Cardiology and Cardiovascular Medicine, medicine.medical_specialty, Renal function, Heart failure, MESH: Mineralocorticoid Receptor Antagonists, 03 medical and health sciences, Angiotensin Receptor Antagonists, Kidney function, Renin angiotensin aldosterone system inhibition, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Internal medicine, Renin–angiotensin system, medicine, Humans, In patient, MESH: Humans, business.industry, MESH: Tetrazoles, Biphenyl Compounds, MESH: Time Factors, Stroke Volume, medicine.disease, MESH: Randomized Controlled Trials as Topic, MESH: Heart Failure, Potassium, business
Abstract

International audience; Numerous registries, including the most recent ESC Euro-observational registry, have reported a large and persistent gap between real-life practice in the use of life-saving evidence-based therapies (such as renin angiotensin antagonists, beta-blockers, mineralocorticoid receptor antagonists) and recommended practices in international guidelines. Although the use of multiple renin angiotensin aldosterone system-inhibitors is associated with the development of worsening renal function and hyperkalemia in patients with heart failure and reduced ejection fraction, increased efforts should be expended to initiate and maintain target doses of these agents so as to provide their benefits on mortality and hospitalizations for heart failure.

Published
2014
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11. Emerging cardiovascular indications of mineralocorticoid receptor antagonists

Author

Yasir Parviz, Abdallah Al-Mohammad, Faiez Zannad, David Adlam, Javaid Iqbal, Bertram Pitt, Sheffield Teaching Hospitals National Health Service Foundation Trust, Manchester Heart Centre, Manchester Royal Infirmary, University of Michigan [Ann Arbor], University of Michigan System, Glenfield Hospital, Centre d'investigation clinique [Nancy] (CIC), Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Cardiologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), and Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)

Subjects
Endocrinology, Diabetes and Metabolism, Severity of Illness Index, Sudden cardiac death, Coronary artery disease, chemistry.chemical_compound, Endocrinology, Mineralocorticoid receptor, MESH: Receptors, Mineralocorticoid, MESH: Animals, Mineralocorticoid Receptor Antagonists, valvular heart disease, 3. Good health, Eplerenone, MESH: Arrhythmias, Cardiac, spironolactone, Cardiovascular Diseases, Cardiology, Disease Progression, MESH: Disease Progression, MESH: Cardiovascular Agents, medicine.drug, medicine.medical_specialty, Hypertension, Pulmonary, MESH: Mineralocorticoid Receptor Antagonists, Models, Biological, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Internal medicine, MESH: Severity of Illness Index, medicine, MESH: Off-Label Use, Animals, Humans, eplerenone, mineralocorticoid receptor, Heart Failure, MESH: Humans, MESH: Hypertension, Pulmonary, business.industry, MESH: Models, Biological, MESH: Cardiovascular Diseases, MESH: Death, Sudden, Cardiac, Arrhythmias, Cardiac, Cardiovascular Agents, novel indications, Off-Label Use, medicine.disease, Death, Sudden, Cardiac, Receptors, Mineralocorticoid, chemistry, Heart failure, MESH: Heart Failure, Spironolactone, business, Heart failure with preserved ejection fraction
Abstract

International audience; Mineralocorticoid receptor (MR) antagonism is a well-established treatment modality for patients with hypertension, heart failure, and left ventricular systolic dysfunction (LVSD) post-myocardial infarction (MI). There are emerging data showing potential benefits of MR antagonists in other cardiovascular conditions. Studies have shown association between MR activation and the development of myocardial fibrosis, coronary artery disease, metabolic syndrome, and cerebrovascular diseases. This review examines the preclinical and clinical data of MR antagonists for novel indications including heart failure with preserved ejection fraction (HFPEF), pulmonary arterial hypertension (PAH), arrhythmia, sudden cardiac death, valvular heart disease, metabolic syndrome, renal disease, and stroke. MR antagonists are not licensed for these conditions yet; however, emerging data suggest that indication for MR antagonists are likely to broaden; further studies are warranted.

Published
2014
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12. Regional differences in heart failure with preserved ejection fraction trials: when nephrology meets cardiology but east does not meet west

Author

Faiez Zannad, Patrick Rossignol, Centre d'investigation clinique [Nancy] (CIC), Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM), Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], Service de Cardiologie [CHRU Nancy], and Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)

Subjects
Nephrology, Male, Internationality, MESH: Geography, MESH: Rosuvastatin Calcium, MESH: Sulfonamides, Tetrazoles, 030204 cardiovascular system & hematology, Spironolactone, MESH: Stroke Volume, chemistry.chemical_compound, 0302 clinical medicine, 030212 general & internal medicine, Rosuvastatin Calcium, kidney function, ComputingMilieux_MISCELLANEOUS, Mineralocorticoid Receptor Antagonists, Sulfonamides, Ejection fraction, clinical trials as topic, Geography, 3. Good health, MESH: Patients, MESH: Spironolactone, Cardiology, ventricular function, mineralocorticoids, Female, Cardiology and Cardiovascular Medicine, MESH: Biphenyl Compounds, Cardiac function curve, medicine.medical_specialty, Patients, MESH: Mineralocorticoid Receptor Antagonists, 03 medical and health sciences, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, left, Physiology (medical), Internal medicine, Post-hoc analysis, medicine, Humans, Heart Failure, aldosterone, MESH: Humans, business.industry, MESH: Tetrazoles, Biphenyl Compounds, Editorials, Stroke Volume, Irbesartan, medicine.disease, MESH: Male, Fluorobenzenes, MESH: Fluorobenzenes, Blood pressure, Pyrimidines, chemistry, MESH: Pyrimidines, Heart failure, MESH: Heart Failure, MESH: Internationality, Benzimidazoles, MESH: Benzimidazoles, business, Heart failure with preserved ejection fraction, MESH: Female
Abstract

In heart failure (HF) with reduced ejection fraction (HF-REF), renin-angiotensin-aldosterone system (RAAS) inhibitors are the Level 1A evidence-based cornerstones of pharmacological treatment. As a result of trial-based progress in medical therapy in the last 2 decades, mortality associated with HF-REF has declined almost 3-fold. In sharp contrast, HF with preserved ejection fraction (HF-PEF) is still lacking evidence-based therapies.1,2 Indeed, the 3 major outcome trials performed in HF-PEF with RAAS inhibitors did not meet their primary end points.3–5 A post hoc analysis of the latest trial, TOPCAT (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist), identified an unusually large difference (≈4-fold) in the placebo group primary event rate of patients randomized from Russia and Georgia (Russia/Georgia) compared with those enrolled from the United States, Argentina, Brazil, and Canada (ie, the Americas).5 Articles see p 34 and p 43 In an effort to better understand this regional heterogeneity, in this issue of Circulation , Pfeffer et al6 performed a comprehensive assessment of clinically relevant variables that may have led to such striking regional discrepancies in terms of patient response to spironolactone. Beyond the inherent limitations of any post hoc analysis, the present data provide major insights into the TOPCAT results that may help change practice in HF-PEF, given the lack of other available therapy in this syndrome. Within each region, the randomized treatment groups were well balanced, whereas between these regions, for almost every variable, baseline characteristics were distinctly different. Over and above the differences in baseline features, the magnitude of changes in blood pressure, kidney function, and potassium kinetics in patients receiving spironolactone was strikingly different across the different geographical areas, being strikingly less pronounced in patients from Russia/Georgia. In the Americas, these changes were more in line with that …

Published
2014
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13. Early eplerenone treatment in patients with acute ST-elevation myocardial infarction without heart failure: The Randomized Double-Blind Reminder Study

Author

Rolf Wachter, Gerald Tremblay, Harry Shi, Anoop Chauhan, Antonio Fernández Ortiz, Miguel Fiol Sala, Jerzy Lewczuk, Andrew Grieve, Rainer Hambrecht, Pierre Coste, Jean-Philippe Collet, J. M. Ten Berg, Jan Vojacek, J. Herrman, Witold Zmuda, Juan Ramon Rey Blas, Emmanuel Teiger, Jaroslav Sumbal, David Smith, Faiez Zannad, Geza Lupkovics, Karol Micko, Johann Bauersachs, Minakshi Madan, Cosme Garcia Garcia, Jerzy Gorny, Marcus Flather, Robert C. Welsh, Carlos Perez Muñoz, David Fitchett, Ruth H. Strasser, Karsten Sydow, Robin A.P. Weir, Miguel Orri, Michel Barboteu, Thomas Münzel, Gilles Montalescot, Georg Noll, Harald Mudra, János Tomcsányi, Serge Lepage, W. Stuart Hillis, Jiri Kettner, Roman Margoczy, Csaba András Dézsi, Thomas N. Martin, Jacek Kubica, Gilles Zemour, Franciso Ridocci Soriano, Dawn L. Adamson, Stephan Steiner, Marian Hranai, Filippatos Gerasimos, Farqad Alamgir, Jean-Lucien Rouleau, Bruce Sussex, Martin Hutyra, Gregory Y.H. Lip, Dimitros Alexopoulos, Michael Böhm, Graham C. Wong, Dominique Ducos, Michel Galinier, Bertram Pitt, Eva Turgonyi, Petr Ostadal, Christian W. Hamm, Freek W.A. Verheugt, Carsten Tschöpe, Esteban López de Sá, Vlassios N Pyrgakis, Jindrich Spinar, Blair J. O'Neill, Hubertus Heuer, Gerhard Hauf, John Vincent, Nikos Werner, David E. Newby, Frantisek Kovar, Dimitrios Babalis, Yves Cottin, Peter Polgar, Gerry P McCann, Xavier Bosch Genover, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), University of Michigan [Ann Arbor], University of Michigan System, Hospital Universitario La Paz, Kerckhoff-Klinik, Norwich Medical School, University of East Anglia [Norwich] (UEA), Onze Lieve Vrouwe Gasthuis (OLVG), Pfizer, Pfizer Ltd, Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), CHU Pontchaillou [Rennes], LAboratoire de Modélisation Pluridisciplinaire et Simulations (LAMPS), Université de Perpignan Via Domitia (UPVD), CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire Avancé de Spectroscopie pour les Intéractions la Réactivité et l'Environnement - UMR 8516 (LASIRE), Institut de Chimie du CNRS (INC)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Conception, synthèse et vectorisation de biomolécules. (CSVB), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Departamento de Fisica Teorica C-XI (FTUAM), Universidad Autónoma de Madrid (UAM), LAboratoire de Mathématiques et PhySique (LAMPS), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Chimie du CNRS (INC)-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Centrale Lille Institut (CLIL), Université Paris Descartes - Paris 5 (UPD5)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut Curie [Paris], Universidad Autonoma de Madrid (UAM), Institut de Physique du Globe de Paris (IPGP), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut national des sciences de l'Univers (INSU - CNRS)-IPG PARIS-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Centre National de la Recherche Scientifique (CNRS), Service de Cardiologie, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Laboratoire de Spectrochimie Infrarouge et Raman - UMR 8516 (LASIR), Centre National de la Recherche Scientifique (CNRS)-Université de Lille, and Institut Curie-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)

Subjects
Male, 030204 cardiovascular system & hematology, Spironolactone, MESH: Length of Stay, 0302 clinical medicine, Clinical endpoint, MESH: Double-Blind Method, 030212 general & internal medicine, Myocardial infarction, MESH: Treatment Outcome, Ejection fraction, MESH: Middle Aged, Hazard ratio, Middle Aged, Brain natriuretic peptide, 3. Good health, Eplerenone, MESH: Myocardial Infarction, Treatment Outcome, MESH: Spironolactone, Cardiology, Female, Cardiology and Cardiovascular Medicine, medicine.drug, medicine.medical_specialty, MESH: Mineralocorticoid Receptor Antagonists, Placebo, Patient Readmission, Mineralocorticoid receptor antagonists, 03 medical and health sciences, Double-Blind Method, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Internal medicine, medicine, MESH: Patient Readmission, Humans, cardiovascular diseases, Heart Failure, MESH: Humans, business.industry, Length of Stay, medicine.disease, MESH: Male, B-type natriuretic peptide, Heart failure, MESH: Heart Failure, Potassium, business, MESH: Female
Abstract

International audience; AIMS:We aimed to assess the impact of eplerenone on cardiovascular (CV) outcomes in STEMI without known heart failure, when initiated within 24 h of symptom onset.METHODS AND RESULTS:In this randomized, placebo-controlled, double-blind trial, we assigned 1012 patients with acute STEMI and without a history of heart failure to receive either eplerenone (25-50 mg once daily) or placebo in addition to standard therapy. The primary endpoint was the composite of CV mortality, re-hospitalization, or, extended initial hospital stay, due to diagnosis of HF, sustained ventricular tachycardia or fibrillation, ejection fraction ≤40%, or elevated BNP/NT-proBNP at 1 month or more after randomization. BNP elevation was defined as BNP levels or values above 200 pg/mL or NT-proBNP values above 450 pg/mL (in patients aged below 50); above 900 pg/mL (age 50-75 years) or above 1800 pg/mL (patients older than 75). After a mean follow-up of 10.5 months, the primary endpoint occurred in 92 patients (18.2%) in the eplerenone group and in 149 patients (29.4%) in the placebo group [adjusted hazard ratio (HR), 0.58; 95% confidence interval (CI), 0.45-0.76; P < 0.0001]. The primary endpoint was driven by a high BNP/NT-proBNP level (adjusted HR, 0.60; 95% CI, 0.45-0.79; P < 0.0003). Adverse event rates were similar in both groups. Serum potassium levels exceeded 5.5 mmol/L in 5.6 vs. 3.2% (P = 0.09) and were below 3.5 mmol/L in 1.4 vs. 5.6% of patients (P = 0.0002), in the eplerenone and placebo groups, respectively.CONCLUSION:The addition of eplerenone during the acute phase of STEMI was safe and well tolerated. It reduced the primary endpoint over a mean 13 months follow-up mostly because of significantly lower BNP/NT-proBNP levels. Additional studies are needed to clarify the role of early use of MRAs in STEMI patients without heart failure.CLINICAL TRIAL REGISTRATION:NCT01176968.

Published
2014
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14. Anti-androgen treatments

Author

Sylvie Salenave, Anne Bachelot, Véronique Kerlan, Nathalie Chabbert-Buffet, Marie-Béatrice Galand-Portier, Endocrinologie moléculaire, Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'endocrinologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Groupe d'Etude de la Thrombose de Bretagne Occidentale (GETBO), Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO)-Université de Brest (UBO), Service d'Endocrinologie (CHRU - Endocrino), and Centre Hospitalier Régional Universitaire de Brest (CHRU Brest)

Subjects
Hirsutism, [SDV]Life Sciences [q-bio], Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Spironolactone, Antiandrogen, MESH: Estrogens, Flutamide, MESH: Cyproterone Acetate, Gonadotropin-Releasing Hormone, chemistry.chemical_compound, 0302 clinical medicine, Endocrinology, MESH: Gonadotropin-Releasing Hormone, 030212 general & internal medicine, Laser hair removal, hirsutism, Acne, Mineralocorticoid Receptor Antagonists, 030219 obstetrics & reproductive medicine, Finasteride, Cyproterone acetate, MESH: Hirsutism, General Medicine, 3. Good health, MESH: Androgen Antagonists, MESH: Spironolactone, Female, medicine.medical_specialty, medicine.drug_class, MESH: Mineralocorticoid Receptor Antagonists, MESH: Hyperandrogenism, 03 medical and health sciences, medicine, Humans, Cyproterone Acetate, Gynecology, MESH: Humans, business.industry, Androgen Antagonists, Estrogens, MESH: Flutamide, medicine.disease, MESH: Finasteride, chemistry, MESH: Progestins, Progestins, business, Hyperandrogenism, MESH: Female
Abstract

International audience; 1. Estrogen plus progestin contraceptives (EPP) are the first-line treatment of moderate hirsutism and acne in women of child bearing age (grade C). 2. CPA, 50mg/day, 20 days out of 28, associated with estrogen is the first-line treatment of "moderate to severe hirsutism" in women of childbearing age (grade C). 3. Spironolactone, given as a contraceptive, can be proposed as a second-line treatment in case of side effects or counter-indications to CPA in moderate to severe hirsutism (grade C) in women of childbearing age. No market authorization in this indication. 4. Flutamide or Finasteride are "only" to be used under the guise of contraception as a "thirdline therapy" in cases of severe hirsutism, the presence of side effects or counter-indications to EPP, CPA 50mg/day or spironolactone (grade C). No market authorization in this indication 5. There is no indication for GnRH analogs as an anti-androgen treatment in women of childbearing age given the current therapeutic alternatives (grade C) 6. Only long-term hair removal treatments can be proposed (grade C): electrolysis or laser hair removal.

Published
2009
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