Cardiac myosin activators for heart failure therapy: focus on omecamtiv mecarbil

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Abstract

Heart failure continues to be a major global health problem with a pronounced impact on morbidity and mortality and very limited drug treatment options especially with regard to inotropic therapy. Omecamtiv mecarbil is a first-in-class cardiac myosin activator, which increases the proportion of myosin heads that are tightly bound to actin and creates a force-producing state that is not associated with cytosolic calcium accumulation. Phase I and phase II studies have shown that it is safe and well tolerated. It produces dose-dependent increases in systolic ejection time (SET), stroke volume (SV), left ventricular ejection fraction (LVEF), and fractional shortening. In the ATOMIC-AHF trial, intravenous (IV) omecamtiv mecarbil did not improve dyspnoea overall but may have improved it in a high-dose group of acute heart failure patients. It did, however, increase SET, decrease left ventricular end-systolic diameter, and was well tolerated. The COSMIC-HF trial showed that a pharmacokinetic-based dose-titration strategy of oral omecamtiv mecarbil improved cardiac function and reduced ventricular diameters compared to placebo and had a similar safety profile. It also significantly reduced plasma N-terminalpro B-type natriuretic peptide compared with placebo. The GALACTIC-HF trial is now underway and will compare omecamtiv mecarbil with placebo when added to current heart failure standard treatment in patients with chronic heart failure and reduced LVEF. It is expected to be completed in January 2021. The ongoing range of preclinical and clinical research on omecamtiv mecarbil will further elucidate its full range of pharmacological effects and its clinical usefulness in heart failure.

Keywords: heart failure, myosin activator, omecamtiv mecarbil.

Citation: Kaplinsky E, Mallarkey G. Cardiac myosin activators for heart failure therapy: focus on omecamtiv mecarbil. Drugs in Context 2018; 7: 212518. DOI: 10.7573/dic.212518

Disclosure and potential conflicts of interest: The authors declare no conflict of interest in the publication of this article. http://www.drugsincontext.com/wp-content/uploads/2018/04/dic.212518-COI.pdf

Acknowledgements: EK performed the initial clinical review and draft manuscript. GM provided pharmacological input and technical writing and editing skills, and both worked together on the revision.

Funding declaration: There was no funding associated with the preparation of this article.

Copyright: Copyright © 2018 Kaplinsky E, Mallarkey G. Published by Drugs in Context under Creative Commons License Deed CC BY NC ND 4.0 which allows anyone to copy, distribute, and transmit the article provided it is properly attributed in the manner specified below. No commercial use without permission.

Correct attribution: Copyright © 2018 Kaplinsky E, Mallarkey G. https://doi.org/10.7573/dic.212518. Published by Drugs in Context under Creative Commons License Deed CC BY NC ND 4.0.

Article URL: http://www.drugsincontext.com/cardiac-myosin-activators-for-heart-failure-therapy-focus-on-omecamtiv-mecarbil

Correspondence: Edgardo Kaplinsky, Cardiology Unit, Medicine Department, Hospital Municipal de Badalona, Vía Augusta Av. 9–13 (08911), Badalona, Spain. ejkaplinsky@gmail.com

Provenance: invited; externally peer reviewed.

Submitted: 28 November 2017; Peer review comments to author: 19 February 2018; Revised manuscript received: 2 April 2018; Accepted: 3 April 2018; Publication date: 23 April 2018.

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