PMID- 35325102
OWN - NLM
STAT- MEDLINE
DCOM- 20220615
LR  - 20220804
IS  - 1522-9645 (Electronic)
IS  - 0195-668X (Linking)
VI  - 43
IP  - 23
DP  - 2022 Jun 14
TI  - Influence of atrial fibrillation on efficacy and safety of omecamtiv mecarbil in 
      heart failure: the GALACTIC-HF trial.
PG  - 2212-2220
LID - 10.1093/eurheartj/ehac144 [doi]
AB  - AIMS: In GALACTIC-HF, the cardiac myosin activator omecamtiv mecarbil compared 
      with placebo reduced the risk of heart failure events or cardiovascular death in 
      patients with heart failure with reduced ejection fraction. We explored the 
      influence of atrial fibrillation or flutter (AFF) on the effectiveness of 
      omecamtiv mecarbil. METHODS AND RESULTS: GALACTIC-HF enrolled patients with New 
      York Heart Association (NYHA) Class II-IV heart failure, left ventricular 
      ejection fraction </=35%, and elevated natriuretic peptides. We assessed whether 
      the presence or absence of AFF, a pre-specified subgroup, modified the treatment 
      effect for the primary and secondary outcomes, and additionally explored effect 
      modification in patients who were or were not receiving digoxin. Patients with 
      AFF (n = 2245, 27%) were older, more likely to be randomized as an inpatient, 
      less likely to have a history of ischaemic aetiology or myocardial infarction, 
      had a worse NYHA class, worse quality of life, lower estimated glomerular 
      filtration rate, and higher N-terminal pro-B-type natriuretic peptide. The 
      treatment effect of omecamtiv mecarbil was modified by baseline AFF (interaction 
      P = 0.012), with patients without AFF at baseline deriving greater benefit. The 
      worsening of the treatment effect by baseline AFF was significantly more 
      pronounced in digoxin users than in non-users (interaction P = 0.007); there was 
      minimal evidence of effect modification in those patients not using digoxin 
      (P = 0.47) or in digoxin users not in AFF. CONCLUSION: Patients in AFF at 
      baseline were less likely to benefit from omecamtiv mecarbil than patients 
      without AFF, although the attenuation of the treatment effect was 
      disproportionally concentrated in patients with AFF who were also receiving 
      digoxin.Clinical Trial Registration: NCT02929329.
CI  - (c) The Author(s) 2022. Published by Oxford University Press on behalf of European 
      Society of Cardiology. All rights reserved. For permissions, please e-mail: 
      journals.permissions@oup.com.
FAU - Solomon, Scott D
AU  - Solomon SD
AUID- ORCID: 0000-0003-3698-9597
AD  - Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, 
      Boston, MA, USA.
FAU - Claggett, Brian L
AU  - Claggett BL
AD  - Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, 
      Boston, MA, USA.
FAU - Miao, Zi Michael
AU  - Miao ZM
AUID- ORCID: 0000-0002-2377-1444
AD  - Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, 
      Boston, MA, USA.
FAU - Diaz, Rafael
AU  - Diaz R
AD  - Estudios Clinicos Latino America (ECLA), Rosario, Argentina.
FAU - Felker, G Michael
AU  - Felker GM
AD  - Division of Cardiology, Duke University School of Medicine and Duke Clinical 
      Research Institute, Durham, NC, USA.
FAU - McMurray, John J V
AU  - McMurray JJV
AD  - British Heart Foundation, Cardiovascular Research Centre, University of Glasgow, 
      Glasgow, UK.
FAU - Metra, Marco
AU  - Metra M
AUID- ORCID: 0000-0001-6691-8568
AD  - Division of Cardiology, ASST Spedali Civili, Department of Medical and Surgical 
      Specialties, Radiological Sciences, and Public Health, University of Brescia, 
      Brescia, Italy.
FAU - Corbalan, Ramon
AU  - Corbalan R
AUID- ORCID: 0000-0002-4675-6191
AD  - Cardiovascular Division, School of Medicine Pontificia Universidad Catolica de 
      Chile, Santiago, Chile.
FAU - Filippatos, Gerasimos
AU  - Filippatos G
AUID- ORCID: 0000-0002-5640-0332
AD  - Department of Cardiology, Athens University Hospital Attikon, National and 
      Kapodistrian University of Athens, Athens, Greece.
FAU - Goudev, Assen R
AU  - Goudev AR
AD  - Department of Cardiology, Queen Giovanna University Hospital, Sofia, Bulgaria.
FAU - Mareev, Viatcheslav
AU  - Mareev V
AUID- ORCID: 0000-0002-7285-2048
AD  - University Clinic of M.V. Lomonosov Moscow State University, Moscow, Russia.
FAU - Serpytis, Pranas
AU  - Serpytis P
AD  - Vilnius University, Medical Faculty, Vilnius, Lithuania.
FAU - Suter, Thomas
AU  - Suter T
AD  - Department of Cardiology, Inselspital, Bern University Hospital, University of 
      Bern, Bern, Switzerland.
FAU - Yilmaz, Mehmet B
AU  - Yilmaz MB
AUID- ORCID: 0000-0002-8169-8628
AD  - Department of Cardiology, Dokuz Eylul University, Izmir, Turkey.
FAU - Zannad, Faiez
AU  - Zannad F
AUID- ORCID: 0000-0001-7456-1570
AD  - Universite de Lorraine, Centre Hospitalier Regional Universitaire de Nancy, 
      Inserm CIC, Nancy, France.
FAU - Kupfer, Stuart
AU  - Kupfer S
AUID- ORCID: 0000-0002-5469-1287
AD  - Cytokinetics, Inc., South San Francisco, CA, USA.
FAU - Heitner, Stephen B
AU  - Heitner SB
AD  - Cytokinetics, Inc., South San Francisco, CA, USA.
FAU - Malik, Fady I
AU  - Malik FI
AUID- ORCID: 0000-0002-5597-5759
AD  - Cytokinetics, Inc., South San Francisco, CA, USA.
FAU - Teerlink, John R
AU  - Teerlink JR
AUID- ORCID: 0000-0001-9527-0852
AD  - Section of Cardiology, San Francisco Veterans Affairs Medical Center and School 
      of Medicine, University of California San Francisco, San Francisco, CA, USA.
LA  - eng
SI  - ClinicalTrials.gov/NCT02929329
PT  - Journal Article
PT  - Randomized Controlled Trial
PL  - England
TA  - Eur Heart J
JT  - European heart journal
JID - 8006263
RN  - 2M19539ERK (omecamtiv mecarbil)
RN  - 73K4184T59 (Digoxin)
RN  - 8W8T17847W (Urea)
SB  - IM
CIN - Eur Heart J. 2022 Apr 20;:. PMID: 35441665
EIN - Eur Heart J. 2022 Jun 18;:. PMID: 35715934
MH  - *Atrial Fibrillation/complications
MH  - Atrial Flutter
MH  - Digoxin/therapeutic use
MH  - *Heart Failure/drug therapy
MH  - Humans
MH  - Quality of Life
MH  - Stroke Volume
MH  - *Urea/adverse effects/analogs & derivatives
MH  - Ventricular Function, Left
OTO - NOTNLM
OT  - Atrial fibrillation
OT  - Digoxin
OT  - Heart failure
OT  - Myosin activator
EDAT- 2022/03/25 06:00
MHDA- 2022/06/16 06:00
CRDT- 2022/03/24 17:25
PHST- 2021/09/16 00:00 [received]
PHST- 2022/02/09 00:00 [revised]
PHST- 2022/03/07 00:00 [accepted]
PHST- 2022/03/25 06:00 [pubmed]
PHST- 2022/06/16 06:00 [medline]
PHST- 2022/03/24 17:25 [entrez]
AID - 6552734 [pii]
AID - 10.1093/eurheartj/ehac144 [doi]
PST - ppublish
SO  - Eur Heart J. 2022 Jun 14;43(23):2212-2220. doi: 10.1093/eurheartj/ehac144.