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Acute Treatment With Omecamtiv Mecarbil to Increase Contractility in Acute Heart Failure: The ATOMIC-AHF Study.

Publication ,  Journal Article
Teerlink, JR; Felker, GM; McMurray, JJV; Ponikowski, P; Metra, M; Filippatos, GS; Ezekowitz, JA; Dickstein, K; Cleland, JGF; Kim, JB; Lei, L ...
Published in: J Am Coll Cardiol
March 29, 2016

BACKGROUND: Omecamtiv mecarbil (OM) is a selective cardiac myosin activator that increases myocardial function in healthy volunteers and in patients with chronic heart failure. OBJECTIVES: This study evaluated the pharmacokinetics, pharmacodynamics, tolerability, safety, and efficacy of OM in patients with acute heart failure (AHF). METHODS: Patients admitted for AHF with left ventricular ejection fraction ≤40%, dyspnea, and elevated plasma concentrations of natriuretic peptides were randomized to receive a double-blind, 48-h intravenous infusion of placebo or OM in 3 sequential, escalating-dose cohorts. RESULTS: In 606 patients, OM did not improve the primary endpoint of dyspnea relief (3 OM dose groups and pooled placebo: placebo, 41%; OM cohort 1, 42%; cohort 2, 47%; cohort 3, 51%; p = 0.33) or any of the secondary outcomes studied. In supplemental, pre-specified analyses, OM resulted in greater dyspnea relief at 48 h (placebo, 37% vs. OM, 51%; p = 0.034) and through 5 days (p = 0.038) in the high-dose cohort. OM exerted plasma concentration-related increases in left ventricular systolic ejection time (p < 0.0001) and decreases in end-systolic dimension (p < 0.05). The adverse event profile and tolerability of OM were similar to those of placebo, without increases in ventricular or supraventricular tachyarrhythmias. Plasma troponin concentrations were higher in OM-treated patients compared with placebo (median difference at 48 h, 0.004 ng/ml), but with no obvious relationship with OM concentration (p = 0.95). CONCLUSIONS: In patients with AHF, intravenous OM did not meet the primary endpoint of dyspnea improvement, but it was generally well tolerated, it increased systolic ejection time, and it may have improved dyspnea in the high-dose group. (Acute Treatment with Omecamtiv Mecarbil to Increase Contractility in Acute Heart Failure [ATOMIC-AHF]; NCT01300013).

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Published In

J Am Coll Cardiol

DOI

EISSN

1558-3597

Publication Date

March 29, 2016

Volume

67

Issue

12

Start / End Page

1444 / 1455

Location

United States

Related Subject Headings

  • Young Adult
  • Ventricular Function, Left
  • Urea
  • Troponin
  • Treatment Outcome
  • Stroke Volume
  • Prospective Studies
  • Myocardial Contraction
  • Middle Aged
  • Male
 

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Teerlink, J. R., Felker, G. M., McMurray, J. J. V., Ponikowski, P., Metra, M., Filippatos, G. S., … ATOMIC-AHF Investigators, . (2016). Acute Treatment With Omecamtiv Mecarbil to Increase Contractility in Acute Heart Failure: The ATOMIC-AHF Study. J Am Coll Cardiol, 67(12), 1444–1455. https://doi.org/10.1016/j.jacc.2016.01.031
Teerlink, John R., G Michael Felker, John J. V. McMurray, Piotr Ponikowski, Marco Metra, Gerasimos S. Filippatos, Justin A. Ezekowitz, et al. “Acute Treatment With Omecamtiv Mecarbil to Increase Contractility in Acute Heart Failure: The ATOMIC-AHF Study.J Am Coll Cardiol 67, no. 12 (March 29, 2016): 1444–55. https://doi.org/10.1016/j.jacc.2016.01.031.
Teerlink JR, Felker GM, McMurray JJV, Ponikowski P, Metra M, Filippatos GS, et al. Acute Treatment With Omecamtiv Mecarbil to Increase Contractility in Acute Heart Failure: The ATOMIC-AHF Study. J Am Coll Cardiol. 2016 Mar 29;67(12):1444–55.
Teerlink, John R., et al. “Acute Treatment With Omecamtiv Mecarbil to Increase Contractility in Acute Heart Failure: The ATOMIC-AHF Study.J Am Coll Cardiol, vol. 67, no. 12, Mar. 2016, pp. 1444–55. Pubmed, doi:10.1016/j.jacc.2016.01.031.
Teerlink JR, Felker GM, McMurray JJV, Ponikowski P, Metra M, Filippatos GS, Ezekowitz JA, Dickstein K, Cleland JGF, Kim JB, Lei L, Knusel B, Wolff AA, Malik FI, Wasserman SM, ATOMIC-AHF Investigators. Acute Treatment With Omecamtiv Mecarbil to Increase Contractility in Acute Heart Failure: The ATOMIC-AHF Study. J Am Coll Cardiol. 2016 Mar 29;67(12):1444–1455.
Journal cover image

Published In

J Am Coll Cardiol

DOI

EISSN

1558-3597

Publication Date

March 29, 2016

Volume

67

Issue

12

Start / End Page

1444 / 1455

Location

United States

Related Subject Headings

  • Young Adult
  • Ventricular Function, Left
  • Urea
  • Troponin
  • Treatment Outcome
  • Stroke Volume
  • Prospective Studies
  • Myocardial Contraction
  • Middle Aged
  • Male