Reference : The effects of the cardiac myosin activator, omecamtiv mecarbil, on cardiac function ...
Scientific journals : Article
Human health sciences : Cardiovascular & respiratory systems
http://hdl.handle.net/10993/18380
The effects of the cardiac myosin activator, omecamtiv mecarbil, on cardiac function in systolic heart failure: a double-blind, placebo-controlled, crossover, dose-ranging phase 2 trial.
English
Cleland, John G. F. [> >]
Teerlink, John R. [> >]
Senior, Roxy [> >]
Nifontov, Evgeny M. [> >]
Mc Murray, John J. V. [> >]
Lang, Chim C. [> >]
Tsyrlin, Vitaly A. [> >]
Greenberg, Barry H. [> >]
Mayet, Jamil [> >]
Francis, Darrel P. [> >]
Shaburishvili, Tamaz [> >]
Monaghan, Mark [> >]
Saltzberg, Mitchell [> >]
Neyses, Ludwig mailto [University of Luxembourg > Research Office]
Wasserman, Scott M. [> >]
Lee, Jacqueline H. [> >]
Saikali, Khalil G. [> >]
Clarke, Cyril P. [> >]
Goldman, Jonathan H. [> >]
Wolff, Andrew A. [> >]
Malik, Fady I. [> >]
2011
Lancet
378
9792
676-83
Yes (verified by ORBilu)
International
0140-6736
1474-547X
England
[en] Urea/administration & dosage/adverse effects/analogs & derivatives/pharmacokinetics/therapeutic use ; Ventricular Dysfunction, Left/complications/physiopathology
[en] BACKGROUND: Many patients with heart failure remain symptomatic and have a poor prognosis despite existing treatments. Decreases in myocardial contractility and shortening of ventricular systole are characteristic of systolic heart failure and might be improved by a new therapeutic class, cardiac myosin activators. We report the first study of the cardiac myosin activator, omecamtiv mecarbil, in patients with systolic heart failure. METHODS: We undertook a double-blind, placebo-controlled, crossover, dose-ranging, phase 2 trial investigating the effects of omecamtiv mecarbil (formerly CK-1827452), given intravenously for 2, 24, or 72 h to patients with stable heart failure and left ventricular systolic dysfunction receiving guideline-indicated treatment. Clinical assessment (including vital signs, echocardiograms, and electrocardiographs) and testing of plasma drug concentrations took place during and after completion of each infusion. The primary aim was to assess safety and tolerability of omecamtiv mecarbil. This study is registered at ClinicalTrials.gov, NCT00624442. FINDINGS: 45 patients received 151 infusions of active drug or placebo. Placebo-corrected, concentration-dependent increases in left ventricular ejection time (up to an 80 ms increase from baseline) and stroke volume (up to 9.7 mL) were recorded, associated with a small reduction in heart rate (up to 2.7 beats per min; p<0.0001 for all three measures). Higher plasma concentrations were also associated with reductions in end-systolic (decrease of 15 mL at >500 ng/mL, p=0.0026) and end-diastolic volumes (16 mL, p=0.0096) that might have been more pronounced with increased duration of infusion. Cardiac ischaemia emerged at high plasma concentrations (two patients, plasma concentrations roughly 1750 ng/mL and 1350 ng/mL). For patients tolerant of all study drug infusions, no consistent pattern of adverse events with either dose or duration emerged. INTERPRETATION: Omecamtiv mecarbil improved cardiac function in patients with heart failure caused by left ventricular dysfunction and could be the first in class of a new therapeutic agent. FUNDING: Cytokinetics Inc.
http://hdl.handle.net/10993/18380
10.1016/S0140-6736(11)61126-4
http://www.sciencedirect.com/science/article/pii/S0140673611611264
Copyright (c) 2011 Elsevier Ltd. All rights reserved.

File(s) associated to this reference

Fulltext file(s):

FileCommentaryVersionSizeAccess
Limited access
The eff ects of the cardiac myosin activator, omecamtiv.pdfPublisher postprint200.9 kBRequest a copy

Bookmark and Share SFX Query

All documents in ORBilu are protected by a user license.