Detail
Article
Online article
FT
Medvik - BMC
  • Something wrong with this record ?

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

HD. Duengen, RJ. Kim, D. Zahger, K. Orvin, R. Kornowski, D. Admon, J. Kettner, A. Shimony, C. Otto, M. Becka, F. Kanefendt, AI. Romo, T. Hasin, P. Ostadal, GC. Rojas, M. Senni, GROUP investigators of the CHIARA MIA 2 trial,

. 2020 ; 224 (-) : 129-137. [pub] 20200125

Language English Country United States

Document type Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't

Persistent link   https://www.medvik.cz/link/bmc20024969
E-resources Online Full text

NLK ProQuest Central from 2002-01-01 to 2 months ago
Nursing & Allied Health Database (ProQuest) from 2002-01-01 to 2 months ago
Health & Medicine (ProQuest) from 2002-01-01 to 2 months ago
Health Management Database (ProQuest) from 2002-01-01 to 2 months ago
Public Health Database (ProQuest) from 2002-01-01 to 2 months ago

Links

PubMed 32375104
DOI 10.1016/j.ahj.2020.01.012
Knihovny.cz E-resources

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.

References provided by Crossref.org

000      
00000naa a2200000 a 4500
001      
bmc20024969
003      
CZ-PrNML
005      
20201222154954.0
007      
ta
008      
201125s2020 xxu f 000 0|eng||
009      
AR
024    7_
$a 10.1016/j.ahj.2020.01.012 $2 doi
035    __
$a (PubMed)32375104
040    __
$a ABA008 $b cze $d ABA008 $e AACR2
041    0_
$a eng
044    __
$a xxu
100    1_
$a Duengen, Hans-Dirk $u Department of Internal Medicine, Cardiology, Charité-Universitaetsmedizin, Berlin, Germany.
245    10
$a 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 / $c HD. Duengen, RJ. Kim, D. Zahger, K. Orvin, R. Kornowski, D. Admon, J. Kettner, A. Shimony, C. Otto, M. Becka, F. Kanefendt, AI. Romo, T. Hasin, P. Ostadal, GC. Rojas, M. Senni, GROUP investigators of the CHIARA MIA 2 trial,
520    9_
$a 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.
650    _2
$a chymasy $x antagonisté a inhibitory $7 D053818
650    _2
$a dvojitá slepá metoda $7 D004311
650    _2
$a ženské pohlaví $7 D005260
650    _2
$a srdeční selhání $x diagnóza $x farmakoterapie $x etiologie $7 D006333
650    _2
$a srdeční komory $x diagnostické zobrazování $x patofyziologie $7 D006352
650    _2
$a lidé $7 D006801
650    _2
$a magnetická rezonance kinematografická $7 D019028
650    _2
$a mužské pohlaví $7 D008297
650    _2
$a lidé středního věku $7 D008875
650    _2
$a infarkt myokardu s elevacemi ST úseků $x komplikace $x farmakoterapie $x patofyziologie $7 D000072657
650    _2
$a tepový objem $x fyziologie $7 D013318
650    _2
$a výsledek terapie $7 D016896
650    _2
$a funkce levé komory srdeční $x fyziologie $7 D016277
650    _2
$a remodelace komor $x účinky léků $7 D020257
655    _2
$a časopisecké články $7 D016428
655    _2
$a multicentrická studie $7 D016448
655    _2
$a randomizované kontrolované studie $7 D016449
655    _2
$a práce podpořená grantem $7 D013485
700    1_
$a Kim, Raymond J $u Duke Cardiovascular Magnetic Resonance Center, Duke University Medical Center, Durham, United States.
700    1_
$a Zahger, Doron $u Department of Cardiology, Soroka University Medical Center, Faculty of Health Sciences, Ben Gurion University of the Negev, Beer Sheva, Israel.
700    1_
$a Orvin, Katia $u Rabin Medical Center - Beilinson Campus, Cardiology Division, Petah Tikva, Israel.
700    1_
$a Kornowski, Ran $u Rabin Medical Center - Beilinson Campus, Cardiology Division, Petah Tikva, Israel.
700    1_
$a Admon, Dan $u Hadassah Hebrew University Hospital Ein Kerem, Heart Institute, Jerusalem, Israel.
700    1_
$a Kettner, Jiri $u Institute for Clinical and Experimental Medicine (IKEM), Prague, Czech Republic.
700    1_
$a Shimony, Avraham $u Department of Cardiology, Soroka University Medical Center, Faculty of Health Sciences, Ben Gurion University of the Negev, Beer Sheva, Israel.
700    1_
$a Otto, Christiane $u Experimental Medicine Cardiovascular, Bayer AG, Wuppertal, Germany. Electronic address: christiane.otto@bayer.com.
700    1_
$a Becka, Michael $u Research and Clinical Sciences Statistics, Bayer AG, Wuppertal, Germany.
700    1_
$a Kanefendt, Friederike $u Clinical Pharmacokinetics, Bayer AG, Wuppertal, Germany.
700    1_
$a Romo, Andres Iniguez $u Hospital Alvaro Cunqueiro, Servicio de la Cardiologia, Vigo, Spain.
700    1_
$a Hasin, Tal $u Shaare Zedek Medical Center, Department of Cardiology, Jerusalem, Israel.
700    1_
$a Ostadal, Petr $u Na Homolce Hospital, Prague, Czech Republic.
700    1_
$a Rojas, Gonzalo Calvo $u Hospital Clinic de Barcelona, Barcelona, Spain.
700    1_
$a Senni, Michele $u Division of Cardiology, Cardiovascular Department, Papa Giovanni XXIII Hospital, Bergamo, Italy.
710    2_
$a GROUP investigators of the CHIARA MIA 2 trial
773    0_
$w MED00000228 $t American heart journal $x 1097-6744 $g Roč. 224, č. - (2020), s. 129-137
856    41
$u https://pubmed.ncbi.nlm.nih.gov/32375104 $y Pubmed
910    __
$a ABA008 $b sig $c sign $y a $z 0
990    __
$a 20201125 $b ABA008
991    __
$a 20201222154950 $b ABA008
999    __
$a ok $b bmc $g 1599114 $s 1115655
BAS    __
$a 3
BAS    __
$a PreBMC
BMC    __
$a 2020 $b 224 $c - $d 129-137 $e 20200125 $i 1097-6744 $m The American heart journal $n Am Heart J $x MED00000228
LZP    __
$a Pubmed-20201125

Find record

Citation metrics

Archiving options