Effect of Ejection Fraction on Clinical Outcomes in Patients
Treated With Omecamtiv Mecarbil in GALACTIC-HF

J 2021

Effect of Ejection Fraction on Clinical Outcomes in Patients Treated With Omecamtiv Mecarbil in GALACTIC-HF

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

Basic information

Original name

Effect of Ejection Fraction on Clinical Outcomes in Patients Treated With Omecamtiv Mecarbil in GALACTIC-HF

Authors

TEERLINK, J. R. (guarantor), R. DIAZ, G. M. FELKER, J. J. V. MCMURRAY, M. METRA, S. D. SOLOMON, T. BIERING-SORENSEN, M. BOHM, D. BONDERMAN, J. C. FANG, D. E. LANFEAR, M. LUND, S. I. MOMOMURA, E. O MEARA, P. PONIKOWSKI, Jindřich ŠPINAR (203 Czech Republic, belonging to the institution), J. H. FLORES-ARREDONDO, B. L. CLAGGETT, S. B. HEITNER, S. KUPFER, S. A. ABBASI and F. I. MALIK

Edition

Journal of the American College of Cardiology, New York, Elsevier Science INC, 2021, 0735-1097

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30201 Cardiac and Cardiovascular systems

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 27.203

RIV identification code

RIV/00216224:14110/21:00123766

Organization unit

Faculty of Medicine

DOI

http://dx.doi.org/10.1016/j.jacc.2021.04.065

UT WoS

000671809300001

Keywords in English

cardiovascular outcomes trial; heart failure with reduced ejection fraction; myotrope

Abstract

V originále

BACKGROUND In GALACTIC-HF (Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure) (n = 8,256), the cardiac myosin activator, omecamtiv mecarbil, significantly reduced the primary composite endpoint (PCE) of time-to-first heart failure event or cardiovascular death in patients with heart failure and reduced ejection fraction (EF) (<= 35%). OBJECTIVES The purpose of this study was to evaluate the influence of baseline EF on the therapeutic effect of omecamtiv mecarbil. METHODS Outcomes in patients treated with omecamtiv mecarbil were compared with placebo according to EF. RESULTS The risk of the PCE in the placebo group was nearly 1.8-fold greater in the lowest EF (<= 22%) compared with the highest EF (>= 33%) quartile. Amongst the pre-specified subgroups, EF was the strongest modifier of the treatment effect of omecamtiv mecarbil on the PCE (interaction as continuous variable, p = 0.004). Patients receiving omecamtiv mecarbil had a progressively greater relative and absolute treatment effect as baseline EF decreased, with a 17% relative risk reduction for the PCE in patients with baseline EF <= 22%(n = 2,246; hazard ratio: 0.83; 95% confidence interval: 0.73 to 0.95) compared with patients with EF >= 33% (n =1,750; hazard ratio: 0.99; 95% confidence interval: 0.84 to 1.16; interaction as EF by quartiles, p = 0.013). The absolute reduction in the PCE increased with decreasing EF (EF <= 22%; absolute risk reduction, 7.4 events per 100 patient-years; number needed to treat for 3 years = 11.8), compared with no reduction in the highest EF quartile. CONCLUSIONS In heart failure patients with reduced EF, omecamtiv mecarbil produced greater therapeutic benefit as baseline EF decreased. These findings are consistent with the drug's mechanism of selectively improving systolic function and presents an important opportunity to improve the outcomes in a group of patients at greatest risk. Published by Elsevier on behalf of the American College of Cardiology Foundation.

Citovat

TEERLINK, J. R., R. DIAZ, G. M. FELKER, J. J. V. MCMURRAY, M. METRA, S. D. SOLOMON, T. BIERING-SORENSEN, M. BOHM, D. BONDERMAN, J. C. FANG, D. E. LANFEAR, M. LUND, S. I. MOMOMURA, E. O MEARA, P. PONIKOWSKI, Jindřich ŠPINAR, J. H. FLORES-ARREDONDO, B. L. CLAGGETT, S. B. HEITNER, S. KUPFER, S. A. ABBASI and F. I. MALIK. Effect of Ejection Fraction on Clinical Outcomes in Patients Treated With Omecamtiv Mecarbil in GALACTIC-HF. Journal of the American College of Cardiology. New York: Elsevier Science INC, 2021, vol. 78, No 2, p. 97-108. ISSN 0735-1097. Available from: https://dx.doi.org/10.1016/j.jacc.2021.04.065.

@article{1822718,
   author = {Teerlink, J. R. and Diaz, R. and Felker, G. M. and McMurray, J. J. V. and Metra, M. and Solomon, S. D. and BieringandSorensen, T. and Bohm, M. and Bonderman, D. and Fang, J. C. and Lanfear, D. E. and Lund, M. and Momomura, S. I. and O Meara, E. and Ponikowski, P. and Špinar, Jindřich and FloresandArredondo, J. H. and Claggett, B. L. and Heitner, S. B. and Kupfer, S. and Abbasi, S. A. and Malik, F. I.},
   article_location = {New York},
   article_number = {2},
   doi = {http://dx.doi.org/10.1016/j.jacc.2021.04.065},
   keywords = {cardiovascular outcomes trial; heart failure with reduced ejection fraction; myotrope},
   language = {eng},
   issn = {0735-1097},
   journal = {Journal of the American College of Cardiology},
   title = {Effect of Ejection Fraction on Clinical Outcomes in Patients Treated With Omecamtiv Mecarbil in GALACTIC-HF},
   url = {https://www.sciencedirect.com/science/article/pii/S0735109721049329?via%3Dihub},
   volume = {78},
   year = {2021}
}

TY  - JOUR
ID  - 1822718
AU  - Teerlink, J. R. - Diaz, R. - Felker, G. M. - McMurray, J. J. V. - Metra, M. - Solomon, S. D. - Biering-Sorensen, T. - Bohm, M. - Bonderman, D. - Fang, J. C. - Lanfear, D. E. - Lund, M. - Momomura, S. I. - O Meara, E. - Ponikowski, P. - Špinar, Jindřich - Flores-Arredondo, J. H. - Claggett, B. L. - Heitner, S. B. - Kupfer, S. - Abbasi, S. A. - Malik, F. I.
PY  - 2021
TI  - Effect of Ejection Fraction on Clinical Outcomes in Patients Treated With Omecamtiv Mecarbil in GALACTIC-HF
JF  - Journal of the American College of Cardiology
VL  - 78
IS  - 2
SP  - 97-108
EP  - 97-108
PB  - Elsevier Science INC
SN  - 07351097
KW  - cardiovascular outcomes trial
KW  - heart failure with reduced ejection fraction
KW  - myotrope
UR  - https://www.sciencedirect.com/science/article/pii/S0735109721049329?via%3Dihub
N2  - BACKGROUND In GALACTIC-HF (Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure) (n = 8,256), the cardiac myosin activator, omecamtiv mecarbil, significantly reduced the primary composite endpoint (PCE) of time-to-first heart failure event or cardiovascular death in patients with heart failure and reduced ejection fraction (EF) (<= 35%). OBJECTIVES The purpose of this study was to evaluate the influence of baseline EF on the therapeutic effect of omecamtiv mecarbil. METHODS Outcomes in patients treated with omecamtiv mecarbil were compared with placebo according to EF. RESULTS The risk of the PCE in the placebo group was nearly 1.8-fold greater in the lowest EF (<= 22%) compared with the highest EF (>= 33%) quartile. Amongst the pre-specified subgroups, EF was the strongest modifier of the treatment effect of omecamtiv mecarbil on the PCE (interaction as continuous variable, p = 0.004). Patients receiving omecamtiv mecarbil had a progressively greater relative and absolute treatment effect as baseline EF decreased, with a 17% relative risk reduction for the PCE in patients with baseline EF <= 22%(n = 2,246; hazard ratio: 0.83; 95% confidence interval: 0.73 to 0.95) compared with patients with EF >= 33% (n =1,750; hazard ratio: 0.99; 95% confidence interval: 0.84 to 1.16; interaction as EF by quartiles, p = 0.013). The absolute reduction in the PCE increased with decreasing EF (EF <= 22%; absolute risk reduction, 7.4 events per 100 patient-years; number needed to treat for 3 years = 11.8), compared with no reduction in the highest EF quartile. CONCLUSIONS In heart failure patients with reduced EF, omecamtiv mecarbil produced greater therapeutic benefit as baseline EF decreased. These findings are consistent with the drug's mechanism of selectively improving systolic function and presents an important opportunity to improve the outcomes in a group of patients at greatest risk. Published by Elsevier on behalf of the American College of Cardiology Foundation.
ER  -

TEERLINK, J. R., R. DIAZ, G. M. FELKER, J. J. V. MCMURRAY, M. METRA, S. D. SOLOMON, T. BIERING-SORENSEN, M. BOHM, D. BONDERMAN, J. C. FANG, D. E. LANFEAR, M. LUND, S. I. MOMOMURA, E. O MEARA, P. PONIKOWSKI, Jindřich ŠPINAR, J. H. FLORES-ARREDONDO, B. L. CLAGGETT, S. B. HEITNER, S. KUPFER, S. A. ABBASI and F. I. MALIK. Effect of Ejection Fraction on Clinical Outcomes in Patients Treated With Omecamtiv Mecarbil in GALACTIC-HF. \textit{Journal of the American College of Cardiology}. New York: Elsevier Science INC, 2021, vol.~78, No~2, p.~97-108. ISSN~0735-1097. Available from: https://dx.doi.org/10.1016/j.jacc.2021.04.065.

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