Cardiac Myosin Activation with Omecamtiv Mecarbil in Systolic Heart Failure

被引：416

作者：

Teerlink, John R. ^{[1
,2
]}

Diaz, Rafael ^{[5
]}

Felker, G. Michael ^{[6
,7
,27
]}

McMurray, John J. V. ^{[9
]}

Metra, Marco ^{[12
]}

Solomon, Scott D. ^{[13
]}

Adams, Kirkwood F. ^{[8
]}

Anand, Inder ^{[14
]}

Arias-Mendoza, Alexandra ^{[15
]}

Biering-Sorensen, Tor ^{[16
,17
]}

Bohm, Michael ^{[18
]}

Bonderman, Diana ^{[19
]}

Cleland, John G. F. ^{[10
,11
,28
]}

Corbalan, Ramon ^{[20
]}

Crespo-Leiro, Maria G. ^{[21
]}

Dahlstrom, Ulf ^{[22
,23
,24
]}

Echeverria, Luis E. ^{[25
]}

Fang, James C. ^{[26
]}

Filippatos, Gerasimos ^{[27
]}

Fonseca, Candida ^{[28
]}

Goncalvesova, Eva ^{[29
]}

Goudev, Assen R. ^{[30
]}

Howlett, Jonathan G. ^{[31
,32
]}

Lanfear, David E. ^{[35
]}

Li, Jing ^{[36
]}

Lund, Mayanna ^{[37
]}

Macdonald, Peter ^{[38
]}

Mareev, Viacheslav ^{[39
]}

Momomura, Shin-ichi ^{[40
]}

O'Meara, Eileen ^{[33
,34
]}

Parkhomenko, Alexander ^{[41
]}

Ponikowski, Piotr ^{[42
]}

Ramires, Felix J. A. ^{[43
]}

Serpytis, Pranas ^{[44
]}

Sliwa, Karen ^{[45
]}

Spinar, Jindrich ^{[46
,47
]}

Suter, Thomas M. ^{[48
]}

Tomcsanyi, Janos ^{[49
]}

Vandekerckhove, Hans ^{[50
]}

Vinereanu, Dragos ^{[51
]}

Voors, Adriaan A. ^{[52
]}

Yilmaz, Mehmet B. ^{[53
]}

Zannad, Faiez ^{[54
]}

Sharpsten, Lucie ^{[3
]}

Legg, Jason C. ^{[3
]}

Varin, Claire ^{[54
]}

Honarpour, Narimon ^{[3
]}

Abbasi, Siddique A. ^{[3
]}

Malik, Fady I. ^{[4
]}

Kurtz, Christopher E. ^{[3
]}

机构：

[1] San Francisco VA Med Ctr, Cardiol Sect, San Francisco, CA 94143 USA

[2] Univ Calif San Francisco, Sch Med, San Francisco, CA 94143 USA

[3] Amgen Inc, Thousand Oaks, CA USA

[4] Cytokinetics, San Francisco, CA USA

[5] Estudios Clin Latino Amer, Rosario, Argentina

[6] Duke Univ, Sch Med, Div Cardiol, Durham, NC 27706 USA

[7] Duke Clin Res Inst, Durham, NC USA

[8] Univ N Carolina, Chapel Hill, NC 27515 USA

[9] British Heart Fdn, Cardiovasc Res Ctr, London, England

[10] Univ Glasgow, Robertson Ctr Biostat & Clin Trials, Inst Hlth & Wellbeing, Glasgow, Lanark, Scotland

[11] Imperial Coll, Natl Heart & Lung Inst, London, England

[12] Univ Brescia, ASST Spedali Civili, Cardiol, Dept Med & Surg Specialties Radiol Sci & Publ Hlt, Brescia, Italy

[13] Brigham & Womens Hosp, Div Cardiovasc Med, 75 Francis St, Boston, MA 02115 USA

[14] Univ Minnesota, Minneapolis, MN USA

[15] Inst Nacl Cardiol, Mexico City, DF, Mexico

[16] Univ Copenhagen, Herlev & Gentofte Hosp, Dept Cardiol, Copenhagen, Denmark

[17] Univ Copenhagen, Dept Biomed Sci, Fac Hlth & Med Sci, Copenhagen, Denmark

[18] Saarland Univ, Univ Klinikum Saarlandes, Homburg, Germany

[19] Med Univ Vienna, Vienna, Austria

[20] Pontificia Univ Catolicica Chile, Santiago, Spain

[21] Univ A Coruna, Complexo Hosp Univ A Coruna, Ctr Invest Biomed Red Enfermedades Cardiovasc, Inst Invest Biomed A Coruna, La Coruna, Spain

[22] Linkoping Univ, Dept Cardiol & Hlth, Linkoping, Sweden

[23] Linkoping Univ, Dept Med, Linkoping, Sweden

[24] Linkoping Univ, Dept Caring Sci, Linkoping, Sweden

[25] Fdn Cardiovasc & Colombia, Floridablanca, Colombia

[26] Univ Utah, Salt Lake City, UT USA

[27] Natl & Kapodistrian Univ Athens, Attikon Univ Hosp, Athens, Greece

[28] Univ Nova Lisboa, Fac Ciencias Med, NOVA Med Sch, Hosp S Francisco Xavier,Ctr Hosp Lisboa Ocidental, Lisbon, Portugal

[29] Comenius Univ, Bratislava, Slovakia

[30] Queen Giovanna Univ Hosp & Med Univ, Dept Cardiol, Sofia, Bulgaria

[31] Univ Calgary, Libin Cardiovasc Inst, Calgary, AB, Canada

[32] Univ Calgary, Cumming Sch Med, Calgary, AB, Canada

[33] Montreal Heart Inst, Montreal, PQ, Canada

[34] Univ Montreal, Montreal, PQ, Canada

[35] Henry Ford Hosp, Inst Heart & Vasc, Detroit, MI 48202 USA

[36] Chinese Acad Med Sci & Peking Union Med Coll, Fuwai Hosp, Natl Hlth Commiss Key Lab Clin Res Cardiovasc Med, Natl Clin Res Ctr Cardiovasc Dis, Beijing, Peoples R China

[37] Middlemore Hosp, Auckland, New Zealand

[38] St Vincents Hosp Sydney, Darlinghurst, NSW, Australia

[39] Moscow MV Lomonosov State Univ, Univ Clin Lomonosov, Moscow, Russia

[40] Saitama Citizens Med Ctr, Saitama, Japan

[41] Inst Cardiol, Kiev, Ukraine

[42] Wroclaw Med Univ, Wroclaw, Poland

[43] Univ Sao Paulo, Fac Med, Hosp Clin Fac Med, Inst Coracao, Sao Paulo, Brazil

[44] Vilnius Univ, Vilnius, Lithuania

[45] Univ Cape Town, Cape Town, South Africa

[46] St Ann Hosp, Internal Cardiol Dept, Brno, Czech Republic

[47] Masaryk Univ Brno, Brno, Czech Republic

[48] Univ Bern, Bern Univ Hosp, Inselspital, Dept Cardiol, Bern, Switzerland

[49] St John God Hosp, Budapest, Hungary

[50] AZ St Lucas, Ghent, Belgium

来源：

NEW ENGLAND JOURNAL OF MEDICINE | 2021年 / 384卷 / 02期

关键词：

REDUCED EJECTION FRACTION; CLINICAL-TRIALS; INCREASE CONTRACTILITY; PHASE-2; DESIGN;

D O I：

10.1056/NEJMoa2025797

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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.)

引用

页码：105 / 116

页数：12

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