Effects of the chymase inhibitor fulacimstat on adverse cardiac remodeling after acute myocardial infarction—Results of the Chymase Inhibitor in Adverse Remodeling after Myocardial Infarction (CHIARA MIA) 2 trial
Autor: | Christiane Otto, Michael Becka, Raymond J. Kim, Eugenia Nikolsky, Katia Orvin, Ran Kornowski, Dan Admon, Mercedes Roque, Savina Nodari, Sadrack Oumbe Tiam, Hans-Dirk Duengen, Johann Bauersachs, Ivo Podpera, Felice Achilli, Borja Ibanez, Friederike Kanefendt, Yaron Arbel, Gian Carlo Silvio Marenzi, Gonzalo Calvo Rojas, Petr Hájek, Doron Zahger, Michele Senni, Petr Ostadal, Bernhard Reimers, Hana Linkova, Manuel Martinez Selles, Niels Menck, Avraham Shimony, Jiri Kettner, Jan Fuisting, Tal Hasin, Andrés Íñiguez Romo, Vicente Miro Palau |
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Přispěvatelé: | Duengen, H, Kim, R, Zahger, D, Orvin, K, Kornowski, R, Admon, D, Kettner, J, Shimony, A, Otto, C, Becka, M, Kanefendt, F, Romo, A, Hasin, T, Ostadal, P, Rojas, G, Senni, M, GROUP investigators of the CHIARA MIA, 2 |
Rok vydání: | 2020 |
Předmět: |
Male
medicine.medical_specialty Heart Ventricles Magnetic Resonance Imaging Cine 030204 cardiovascular system & hematology Placebo Ventricular Function Left Heart Ventricle law.invention 03 medical and health sciences Chymases 0302 clinical medicine Double-Blind Method Randomized controlled trial law Internal medicine medicine Humans cardiovascular diseases 030212 general & internal medicine Myocardial infarction Risk factor Heart Failure Ejection fraction Ventricular Remodeling medicine.diagnostic_test business.industry Chymase Stroke Volume Magnetic resonance imaging Middle Aged medicine.disease Treatment Outcome Heart failure Cardiology ST Elevation Myocardial Infarction Female Cardiology and Cardiovascular Medicine business Human |
Zdroj: | American Heart Journal. 224:129-137 |
ISSN: | 0002-8703 |
Popis: | Background Adverse cardiac remodeling is a major risk factor for the development of post myocardial infarction (MI) heart failure (HF). This study investigates the effects of the chymase inhibitor fulacimstat on adverse cardiac remodeling after acute ST-segment-elevation myocardial infarction (STEMI). Methods In this double-blind, randomized, placebo-controlled trial patients with first STEMI were eligible. To preferentially enrich patients at high risk of adverse remodeling, main inclusion criteria were a left-ventricular ejection fraction (LVEF) ≤45% and an infarct size >10% on day 5 to 9 post MI as measured by cardiac MRI. Patients were then randomized to 6 months treatment with either 25 mg fulacimstat (n = 54) or placebo (n = 53) twice daily on top of standard of care starting day 6 to 12 post MI. The changes in LVEF, LV end-diastolic volume index (LVEDVI), and LV end-systolic volume index (LVESVI) from baseline to 6 months were analyzed by a central blinded cardiac MRI core laboratory. Results Fulacimstat was safe and well tolerated and achieved mean total trough concentrations that were approximately tenfold higher than those predicted to be required for minimal therapeutic activity. Comparable changes in LVEF (fulacimstat: 3.5% ± 5.4%, placebo: 4.0% ± 5.0%, P = .69), LVEDVI (fulacimstat: 7.3 ± 13.3 mL/m2, placebo: 5.1 ± 18.9 mL/m2, P = .54), and LVESVI (fulacimstat: 2.3 ± 11.2 mL/m2, placebo: 0.6 ± 14.8 mL/m2, P = .56) were observed in both treatment arms. Conclusion Fulacimstat was safe and well tolerated in patients with left-ventricular dysfunction (LVD) after first STEMI but had no effect on cardiac remodeling. |
Databáze: | OpenAIRE |
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