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The effects of the cardiac myosin activator, omecamtiv mecarbil, on cardiac function in systolic heart failure

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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. / Cleland, John G. F.; Teerlink, John R.; Senior, Roxy; Nifontov, Evgeny M.; McMurray, 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; Wasserman, Scott M.; Lee, Jacqueline H.; Saikali, Khalil G.; Clarke, Cyril P.; Goldman, Jonathan H.; Wolff, Andrew A.; Malik, Fady I.

In: Lancet, Vol. 378, No. 9792, 20.08.2011, p. 676-683.

Research output: Contribution to journalArticle

Harvard

Cleland, JGF, Teerlink, JR, Senior, R, Nifontov, EM, McMurray, JJV, Lang, CC, Tsyrlin, VA, Greenberg, BH, Mayet, J, Francis, DP, Shaburishvili, T, Monaghan, M, Saltzberg, M, Neyses, L, Wasserman, SM, Lee, JH, Saikali, KG, Clarke, CP, Goldman, JH, Wolff, AA & Malik, FI 2011, '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' Lancet, vol 378, no. 9792, pp. 676-683.

APA

Cleland, J. G. F., Teerlink, J. R., Senior, R., Nifontov, E. M., McMurray, J. J. V., Lang, C. C., Tsyrlin, V. A., Greenberg, B. H., Mayet, J., Francis, D. P., Shaburishvili, T., Monaghan, M., Saltzberg, M., Neyses, L., Wasserman, S. M., Lee, J. H., Saikali, K. G., Clarke, C. P., Goldman, J. H., Wolff, A. A., & Malik, F. I. (2011). 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. Lancet, 378(9792), 676-683doi: 10.1016/S0140-6736(11)61126-4

Vancouver

Cleland JGF, Teerlink JR, Senior R, Nifontov EM, McMurray JJV, Lang CC et al. 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. Lancet. 2011 Aug 20;378(9792):676-683.

Author

Cleland, John G. F.; Teerlink, John R.; Senior, Roxy; Nifontov, Evgeny M.; McMurray, 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; Wasserman, Scott M.; Lee, Jacqueline H.; Saikali, Khalil G.; Clarke, Cyril P.; Goldman, Jonathan H.; Wolff, Andrew A.; Malik, Fady I. / 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.

In: Lancet, Vol. 378, No. 9792, 20.08.2011, p. 676-683.

Research output: Contribution to journalArticle

Bibtex - Download

@article{6c0f41f60bdc4ba5a31bc89fff426e0a,
title = "The effects of the cardiac myosin activator, omecamtiv mecarbil, on cardiac function in systolic heart failure",
author = "Cleland, {John G. F.} and Teerlink, {John R.} and Roxy Senior and Nifontov, {Evgeny M.} and McMurray, {John J. V.} and Lang, {Chim C.} and Tsyrlin, {Vitaly A.} and Greenberg, {Barry H.} and Jamil Mayet and Francis, {Darrel P.} and Tamaz Shaburishvili and Mark Monaghan and Mitchell Saltzberg and Ludwig Neyses and Wasserman, {Scott M.} and Lee, {Jacqueline H.} and Saikali, {Khalil G.} and Clarke, {Cyril P.} and Goldman, {Jonathan H.} and Wolff, {Andrew A.} and Malik, {Fady I.}",
year = "2011",
volume = "378",
number = "9792",
pages = "676--683",
journal = "Lancet",
issn = "0140-6736",

}

RIS (suitable for import to EndNote) - Download

TY - JOUR

T1 - The effects of the cardiac myosin activator, omecamtiv mecarbil, on cardiac function in systolic heart failure

T2 - a double-blind, placebo-controlled, crossover, dose-ranging phase 2 trial

A1 - Cleland,John G. F.

A1 - Teerlink,John R.

A1 - Senior,Roxy

A1 - Nifontov,Evgeny M.

A1 - McMurray,John J. V.

A1 - Lang,Chim C.

A1 - Tsyrlin,Vitaly A.

A1 - Greenberg,Barry H.

A1 - Mayet,Jamil

A1 - Francis,Darrel P.

A1 - Shaburishvili,Tamaz

A1 - Monaghan,Mark

A1 - Saltzberg,Mitchell

A1 - Neyses,Ludwig

A1 - Wasserman,Scott M.

A1 - Lee,Jacqueline H.

A1 - Saikali,Khalil G.

A1 - Clarke,Cyril P.

A1 - Goldman,Jonathan H.

A1 - Wolff,Andrew A.

A1 - Malik,Fady I.

AU - Cleland,John G. F.

AU - Teerlink,John R.

AU - Senior,Roxy

AU - Nifontov,Evgeny M.

AU - McMurray,John J. V.

AU - Lang,Chim C.

AU - Tsyrlin,Vitaly A.

AU - Greenberg,Barry H.

AU - Mayet,Jamil

AU - Francis,Darrel P.

AU - Shaburishvili,Tamaz

AU - Monaghan,Mark

AU - Saltzberg,Mitchell

AU - Neyses,Ludwig

AU - Wasserman,Scott M.

AU - Lee,Jacqueline H.

AU - Saikali,Khalil G.

AU - Clarke,Cyril P.

AU - Goldman,Jonathan H.

AU - Wolff,Andrew A.

AU - Malik,Fady I.

PY - 2011/8/20

Y1 - 2011/8/20

N2 - <p>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.</p><p>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.</p><p>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&lt;0.0001 for all three measures). Higher plasma concentrations were also associated with reductions in end-systolic (decrease of 15 mL at &gt;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.</p><p>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.</p>

AB - <p>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.</p><p>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.</p><p>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&lt;0.0001 for all three measures). Higher plasma concentrations were also associated with reductions in end-systolic (decrease of 15 mL at &gt;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.</p><p>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.</p>

KW - RESYNCHRONIZATION THERAPY

KW - CONSCIOUS DOGS

KW - MILRINONE

KW - MORTALITY

U2 - 10.1016/S0140-6736(11)61126-4

DO - 10.1016/S0140-6736(11)61126-4

M1 - Article

JO - Lancet

JF - Lancet

SN - 0140-6736

IS - 9792

VL - 378

SP - 676

EP - 683

ER -

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