Cardiac Myosin Activation with Omecamtiv Mecarbil in Systolic
Heart Failure

J 2021

Cardiac Myosin Activation with Omecamtiv Mecarbil in Systolic Heart Failure

TEERLINK, J. R., R. DIAZ, G. M. FELKER, J. J. V. MCMURRAY, M. METRA et. al.

Basic information

Original name

Cardiac Myosin Activation with Omecamtiv Mecarbil in Systolic Heart Failure

Authors

TEERLINK, J. R. (guarantor), R. DIAZ, G. M. FELKER, J. J. V. MCMURRAY, M. METRA, S. D. SOLOMON, K. F. ADAMS, I. ANAND, A. ARIAS-MENDOZA, T. BIERING-SORENSEN, M. BOHM, D. BONDERMAN, J. G. F. CLELAND, R. CORBALAN, M. G. CRESPO-LEIRO, U. DAHLSTROM, L. E. ECHEVERRIA, J. M. C. FANG, G. FILIPPATOS, C. FONSECA, E. GONCALVESOVA, A. R. GOUDEV, J. G. HOWLETT, D. E.. LANFEAR, J. LI, M. LUND, P. MACDONALD, V. MAREEV, S. I. MOMOMURA, E. O MEARA, A. PARKHOMENKO, P. PONIKOWSKI, F. J. A. RAMIRES, P. SERPYTIS, K. SLIWA, Jindřich ŠPINAR (203 Czech Republic, belonging to the institution), T. M. SUTER, J. TOMCSANYI, H. VANDEKERCKHOVE, D. VINEREANU, A. A. VOORS, M. B. YILMAZ, F. ZANNAD, L. SHARPSTEN, J. C. LEGG, C. VARIN, N. HONARPOUR, S. A. ABBASI, F. I. MALIK and C. E. KURTZ

Edition

New England Journal of Medicine, Waltham, Massachussetts Medical Society, 2021, 0028-4793

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30218 General and internal medicine

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 176.079

RIV identification code

RIV/00216224:14110/21:00121598

Organization unit

Faculty of Medicine

DOI

http://dx.doi.org/10.1056/NEJMoa2025797

UT WoS

000609886200010

Keywords in English

Cardiac Myosin Activation; Omecamtiv Mecarbil; Systolic Heart Failure

Abstract

V originále

Among patients with heart failure and a reduced ejection fraction, those who received the cardiac myosin activator omecamtiv mecarbil had a lower incidence of a composite of heart-failure events or cardiovascular death at a median of 22 months than those who received placebo. Background The selective cardiac myosin activator omecamtiv mecarbil has been shown to improve cardiac function in patients with heart failure with a reduced ejection fraction. Its effect on cardiovascular outcomes is unknown. Methods We randomly assigned 8256 patients (inpatients and outpatients) with symptomatic chronic heart failure and an ejection fraction of 35% or less to receive omecamtiv mecarbil (using pharmacokinetic-guided doses of 25 mg, 37.5 mg, or 50 mg twice daily) or placebo, in addition to standard heart-failure therapy. The primary outcome was a composite of a first heart-failure event (hospitalization or urgent visit for heart failure) or death from cardiovascular causes. Results During a median of 21.8 months, a primary-outcome event occurred in 1523 of 4120 patients (37.0%) in the omecamtiv mecarbil group and in 1607 of 4112 patients (39.1%) in the placebo group (hazard ratio, 0.92; 95% confidence interval [CI], 0.86 to 0.99; P=0.03). A total of 808 patients (19.6%) and 798 patients (19.4%), respectively, died from cardiovascular causes (hazard ratio, 1.01; 95% CI, 0.92 to 1.11). There was no significant difference between groups in the change from baseline on the Kansas City Cardiomyopathy Questionnaire total symptom score. At week 24, the change from baseline for the median N-terminal pro-B-type natriuretic peptide level was 10% lower in the omecamtiv mecarbil group than in the placebo group; the median cardiac troponin I level was 4 ng per liter higher. The frequency of cardiac ischemic and ventricular arrhythmia events was similar in the two groups. Conclusions Among patients with heart failure and a reduced ejection, those who received omecamtiv mecarbil had a lower incidence of a composite of a heart-failure event or death from cardiovascular causes than those who received placebo. (Funded by Amgen and others; GALACTIC-HF ClinicalTrials.gov number, ; EudraCT number, 2016-002299-28.)

Citovat

TEERLINK, J. R., R. DIAZ, G. M. FELKER, J. J. V. MCMURRAY, M. METRA, S. D. SOLOMON, K. F. ADAMS, I. ANAND, A. ARIAS-MENDOZA, T. BIERING-SORENSEN, M. BOHM, D. BONDERMAN, J. G. F. CLELAND, R. CORBALAN, M. G. CRESPO-LEIRO, U. DAHLSTROM, L. E. ECHEVERRIA, J. M. C. FANG, G. FILIPPATOS, C. FONSECA, E. GONCALVESOVA, A. R. GOUDEV, J. G. HOWLETT, D. E.. LANFEAR, J. LI, M. LUND, P. MACDONALD, V. MAREEV, S. I. MOMOMURA, E. O MEARA, A. PARKHOMENKO, P. PONIKOWSKI, F. J. A. RAMIRES, P. SERPYTIS, K. SLIWA, Jindřich ŠPINAR, T. M. SUTER, J. TOMCSANYI, H. VANDEKERCKHOVE, D. VINEREANU, A. A. VOORS, M. B. YILMAZ, F. ZANNAD, L. SHARPSTEN, J. C. LEGG, C. VARIN, N. HONARPOUR, S. A. ABBASI, F. I. MALIK and C. E. KURTZ. Cardiac Myosin Activation with Omecamtiv Mecarbil in Systolic Heart Failure. New England Journal of Medicine. Waltham: Massachussetts Medical Society, 2021, vol. 384, No 2, p. 105-116. ISSN 0028-4793. Available from: https://dx.doi.org/10.1056/NEJMoa2025797.

@article{1769277,
   author = {Teerlink, J. R. and Diaz, R. and Felker, G. M. and McMurray, J. J. V. and Metra, M. and Solomon, S. D. and Adams, K. F. and Anand, I. and AriasandMendoza, A. and BieringandSorensen, T. and Bohm, M. and Bonderman, D. and Cleland, J. G. F. and Corbalan, R. and CrespoandLeiro, M. G. and Dahlstrom, U. and Echeverria, L. E. and Fang, J. M. C. and Filippatos, G. and Fonseca, C. and Goncalvesova, E. and Goudev, A. R. and Howlett, J. G. and Lanfear, D. E.. and Li, J. and Lund, M. and Macdonald, P. and Mareev, V. and Momomura, S. I. and O Meara, E. and Parkhomenko, A. and Ponikowski, P. and Ramires, F. J. A. and Serpytis, P. and Sliwa, K. and Špinar, Jindřich and Suter, T. M. and Tomcsanyi, J. and Vandekerckhove, H. and Vinereanu, D. and Voors, A. A. and Yilmaz, M. B. and Zannad, F. and Sharpsten, L. and Legg, J. C. and Varin, C. and Honarpour, N. and Abbasi, S. A. and Malik, F. I. and Kurtz, C. E.},
   article_location = {Waltham},
   article_number = {2},
   doi = {http://dx.doi.org/10.1056/NEJMoa2025797},
   keywords = {Cardiac Myosin Activation; Omecamtiv Mecarbil; Systolic Heart Failure},
   language = {eng},
   issn = {0028-4793},
   journal = {New England Journal of Medicine},
   title = {Cardiac Myosin Activation with Omecamtiv Mecarbil in Systolic Heart Failure},
   url = {https://www.nejm.org/doi/10.1056/NEJMoa2025797},
   volume = {384},
   year = {2021}
}

TY  - JOUR
ID  - 1769277
AU  - Teerlink, J. R. - Diaz, R. - Felker, G. M. - McMurray, J. J. V. - Metra, M. - Solomon, S. D. - Adams, K. F. - Anand, I. - Arias-Mendoza, A. - Biering-Sorensen, T. - Bohm, M. - Bonderman, D. - Cleland, J. G. F. - Corbalan, R. - Crespo-Leiro, M. G. - Dahlstrom, U. - Echeverria, L. E. - Fang, J. M. C. - Filippatos, G. - Fonseca, C. - Goncalvesova, E. - Goudev, A. R. - Howlett, J. G. - Lanfear, D. E.. - Li, J. - Lund, M. - Macdonald, P. - Mareev, V. - Momomura, S. I. - O Meara, E. - Parkhomenko, A. - Ponikowski, P. - Ramires, F. J. A. - Serpytis, P. - Sliwa, K. - Špinar, Jindřich - Suter, T. M. - Tomcsanyi, J. - Vandekerckhove, H. - Vinereanu, D. - Voors, A. A. - Yilmaz, M. B. - Zannad, F. - Sharpsten, L. - Legg, J. C. - Varin, C. - Honarpour, N. - Abbasi, S. A. - Malik, F. I. - Kurtz, C. E.
PY  - 2021
TI  - Cardiac Myosin Activation with Omecamtiv Mecarbil in Systolic Heart Failure
JF  - New England Journal of Medicine
VL  - 384
IS  - 2
SP  - 105-116
EP  - 105-116
PB  - Massachussetts Medical Society
SN  - 00284793
KW  - Cardiac Myosin Activation
KW  - Omecamtiv Mecarbil
KW  - Systolic Heart Failure
UR  - https://www.nejm.org/doi/10.1056/NEJMoa2025797
N2  - Among patients with heart failure and a reduced ejection fraction, those who received the cardiac myosin activator omecamtiv mecarbil had a lower incidence of a composite of heart-failure events or cardiovascular death at a median of 22 months than those who received placebo. Background The selective cardiac myosin activator omecamtiv mecarbil has been shown to improve cardiac function in patients with heart failure with a reduced ejection fraction. Its effect on cardiovascular outcomes is unknown. Methods We randomly assigned 8256 patients (inpatients and outpatients) with symptomatic chronic heart failure and an ejection fraction of 35% or less to receive omecamtiv mecarbil (using pharmacokinetic-guided doses of 25 mg, 37.5 mg, or 50 mg twice daily) or placebo, in addition to standard heart-failure therapy. The primary outcome was a composite of a first heart-failure event (hospitalization or urgent visit for heart failure) or death from cardiovascular causes. Results During a median of 21.8 months, a primary-outcome event occurred in 1523 of 4120 patients (37.0%) in the omecamtiv mecarbil group and in 1607 of 4112 patients (39.1%) in the placebo group (hazard ratio, 0.92; 95% confidence interval [CI], 0.86 to 0.99; P=0.03). A total of 808 patients (19.6%) and 798 patients (19.4%), respectively, died from cardiovascular causes (hazard ratio, 1.01; 95% CI, 0.92 to 1.11). There was no significant difference between groups in the change from baseline on the Kansas City Cardiomyopathy Questionnaire total symptom score. At week 24, the change from baseline for the median N-terminal pro-B-type natriuretic peptide level was 10% lower in the omecamtiv mecarbil group than in the placebo group; the median cardiac troponin I level was 4 ng per liter higher. The frequency of cardiac ischemic and ventricular arrhythmia events was similar in the two groups. Conclusions Among patients with heart failure and a reduced ejection, those who received omecamtiv mecarbil had a lower incidence of a composite of a heart-failure event or death from cardiovascular causes than those who received placebo. (Funded by Amgen and others; GALACTIC-HF ClinicalTrials.gov number, ; EudraCT number, 2016-002299-28.)
ER  -

TEERLINK, J. R., R. DIAZ, G. M. FELKER, J. J. V. MCMURRAY, M. METRA, S. D. SOLOMON, K. F. ADAMS, I. ANAND, A. ARIAS-MENDOZA, T. BIERING-SORENSEN, M. BOHM, D. BONDERMAN, J. G. F. CLELAND, R. CORBALAN, M. G. CRESPO-LEIRO, U. DAHLSTROM, L. E. ECHEVERRIA, J. M. C. FANG, G. FILIPPATOS, C. FONSECA, E. GONCALVESOVA, A. R. GOUDEV, J. G. HOWLETT, D. E.. LANFEAR, J. LI, M. LUND, P. MACDONALD, V. MAREEV, S. I. MOMOMURA, E. O MEARA, A. PARKHOMENKO, P. PONIKOWSKI, F. J. A. RAMIRES, P. SERPYTIS, K. SLIWA, Jindřich ŠPINAR, T. M. SUTER, J. TOMCSANYI, H. VANDEKERCKHOVE, D. VINEREANU, A. A. VOORS, M. B. YILMAZ, F. ZANNAD, L. SHARPSTEN, J. C. LEGG, C. VARIN, N. HONARPOUR, S. A. ABBASI, F. I. MALIK and C. E. KURTZ. Cardiac Myosin Activation with Omecamtiv Mecarbil in Systolic Heart Failure. \textit{New England Journal of Medicine}. Waltham: Massachussetts Medical Society, 2021, vol.~384, No~2, p.~105-116. ISSN~0028-4793. Available from: https://dx.doi.org/10.1056/NEJMoa2025797.

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