PMID- 31339232
OWN - NLM
STAT- MEDLINE
DCOM- 20200608
LR  - 20211204
IS  - 2055-5822 (Electronic)
IS  - 2055-5822 (Linking)
VI  - 6
IP  - 5
DP  - 2019 Oct
TI  - Background pharmacological therapy in the ANTHEM-HF: comparison to contemporary 
      trials of novel heart failure therapies.
PG  - 1052-1056
LID - 10.1002/ehf2.12484 [doi]
AB  - AIMS: Clinical trials of new heart failure (HF) therapies administer 
      guideline-directed medical therapy (GDMT) as background pharmacologic treatment 
      (BPT). In the ANTHEM-HF Pilot Study, addition of autonomic regulation therapy to 
      GDMT significantly improved left ventricular function, New York Heart Association 
      (NYHA) class, 6 min walk distance, and quality of life in patients with HF with 
      reduced ejection fraction (HFrEF). A post hoc analysis was performed to compare 
      BPT in ANTHEM-HF with two other trials of novel HF therapies: the PARADIGM-HF 
      study of sacubitril-valsartan and the SHIFT study of ivadrabine. All three 
      studies evaluated patients with HFrEF, and the recommendations for use of GDMT 
      were similar. A left ventricular ejection fraction </=40% was required for entry 
      into ANTHEM-HF and PARADIGM-HF and </=35% for SHIFT. NYHA 2 or 3 symptoms were 
      required for entry into ANTHEM-HF, and patients with predominantly NYHA 2 or 3 
      symptoms were enrolled in PARADIGM-HF and SHIFT. METHODS AND RESULTS: Data on BPT 
      were obtained from peer-reviewed publications and the public domain. Pearson's 
      chi(2) test was used to evaluate differences in proportions, and Student's unpaired 
      t-test was used to evaluate differences in mean values. The minimum period of 
      stable GDMT required before randomization was longer in ANTHEM-HF: 3 months vs. 1 
      month in PARADIGM-HF and SHIFT, respectively. When compared with PARADIGM-HF and 
      SHIFT, more patients in ANTHEM-HF received beta-blockers (100% vs. 93% and 89%, P 
      < 0.04 and P < 0.007) and mineralocorticoid receptor antagonists (75% vs. 55% and 
      61%, P < 0.002 and P < 0.03). More patients in PARADIGM-HF received an 
      angiotensin-converting enzyme inhibitor or angiotensin receptor blocker than in 
      ANTHEM-HF or SHIFT (100% vs. 85%, P < 0.0001, and 100% vs. 91%, P < 0.001), which 
      was related to PARADIGM's design. When beta-blocker doses in ANTHEM-HF and SHIFT 
      were compared, significantly fewer patients in ANTHEM-HF received doses >/=100% of 
      target (10% vs. 23%, P < 0.02), and fewer patients tended to receive doses >/=50% 
      of target (17% vs. 26%, P = 0.11). When ANTHEM-HF and PARADIGM-HF were compared, 
      more patients in ANTHEM-HF tended to receive doses >/=100% of target (10% vs. 7%, P 
      = 0.36), and fewer patients tended to receive doses >/=50% of target (17% vs. 20%, 
      P = 0.56). CONCLUSIONS: Background treatment with GDMT in ANTHEM-HF compared 
      favourably with that in two other contemporary trials of new HF therapies. The 
      minimum period of stable GDMT required before randomization was longer, and GDMT 
      remained unchanged for the study's duration. These findings serve to further 
      support the potential role of autonomic regulation therapy as an adjunct to GDMT 
      for patients with HFrEF.
CI  - (c) 2019 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on 
      behalf of the European Society of Cardiology.
FAU - Premchand, Rajendra K
AU  - Premchand RK
AD  - Krishna Institute of Medical Sciences, Secunderabad, India.
FAU - Sharma, Kamal
AU  - Sharma K
AD  - Sanjivani Super Specialty Hospitals, Ahmedabad, India.
FAU - Mittal, Sanjay
AU  - Mittal S
AD  - Medanta, The Medicity, Gurugram, Haryana, India.
FAU - Monteiro, Rufino
AU  - Monteiro R
AD  - Vintage Hospital, Panaji, Goa, India.
FAU - Libbus, Imad
AU  - Libbus I
AD  - LivaNova USA, Inc., Houston, TX, USA.
FAU - Ardell, Jeffrey L
AU  - Ardell JL
AD  - University of California, Los Angeles, Los Angeles, CA, USA.
FAU - Gregory, Douglas D
AU  - Gregory DD
AD  - Clinical Cardiovascular Science Foundation, Boston, MA, USA.
FAU - KenKnight, Bruce H
AU  - KenKnight BH
AD  - LivaNova USA, Inc., Houston, TX, USA.
FAU - Amurthur, Badri
AU  - Amurthur B
AD  - LivaNova USA, Inc., Houston, TX, USA.
FAU - DiCarlo, Lorenzo A
AU  - DiCarlo LA
AD  - LivaNova USA, Inc., Houston, TX, USA.
FAU - Anand, Inder S
AU  - Anand IS
AD  - University of Minnesota (Emeritus), Minneapolis, MN, USA.
LA  - eng
GR  - None/Cyberonics Incorporated, Houston, TX, USA/International
PT  - Clinical Trial
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190724
PL  - England
TA  - ESC Heart Fail
JT  - ESC heart failure
JID - 101669191
RN  - 0 (Adrenergic beta-Antagonists)
RN  - 0 (Aminobutyrates)
RN  - 0 (Angiotensin Receptor Antagonists)
RN  - 0 (Angiotensin-Converting Enzyme Inhibitors)
RN  - 0 (Biphenyl Compounds)
RN  - 0 (Cardiovascular Agents)
RN  - 0 (Drug Combinations)
RN  - 0 (Mineralocorticoid Receptor Antagonists)
RN  - 0 (Tetrazoles)
RN  - 3H48L0LPZQ (Ivabradine)
RN  - 80M03YXJ7I (Valsartan)
RN  - WB8FT61183 (sacubitril and valsartan sodium hydrate drug combination)
SB  - IM
MH  - Adrenergic beta-Antagonists/pharmacology/therapeutic use
MH  - Adult
MH  - Aged
MH  - Aminobutyrates/pharmacology/therapeutic use
MH  - Angiotensin Receptor Antagonists/pharmacology/therapeutic use
MH  - Angiotensin-Converting Enzyme Inhibitors/pharmacology/therapeutic use
MH  - Autonomic Nervous System/*drug effects/physiopathology
MH  - Biphenyl Compounds
MH  - Cardiovascular Agents/pharmacology/therapeutic use
MH  - Drug Combinations
MH  - Female
MH  - Heart Failure/*drug therapy/physiopathology/psychology
MH  - Humans
MH  - Ivabradine/pharmacology/therapeutic use
MH  - Male
MH  - Middle Aged
MH  - Mineralocorticoid Receptor Antagonists/pharmacology/therapeutic use
MH  - Practice Guidelines as Topic/*standards
MH  - Quality of Life
MH  - Stroke Volume/drug effects/physiology
MH  - Tetrazoles/pharmacology/therapeutic use
MH  - Treatment Outcome
MH  - Vagus Nerve Stimulation/methods
MH  - Valsartan
MH  - Ventricular Function, Left/*drug effects/physiology
MH  - Walk Test/methods/statistics & numerical data
PMC - PMC6816059
OTO - NOTNLM
OT  - Autonomic nervous system
OT  - Autonomic regulation therapy
OT  - Guideline-directed medical therapy
OT  - Heart failure
OT  - Neuromodulation
OT  - Vagus nerve stimulation
COIS- R.P., K.S., S.M., and R.M. were compensated by Cyberonics Incorporated for their 
      work as clinical investigators in the ANTHEM-HF Pilot Study. J.L.A. is a 
      researcher in neurocardiology, D.D.G. is a statistician, and I.A. is a clinician, 
      who are contracted as consultants to LivaNova USA Incorporated. L.D.C., B.H.K., 
      and B.A. are employees and shareholders of LivaNova USA Incorporated.
EDAT- 2019/07/25 06:00
MHDA- 2020/06/09 06:00
PMCR- 2019/07/24
CRDT- 2019/07/25 06:00
PHST- 2018/12/03 00:00 [received]
PHST- 2019/05/06 00:00 [revised]
PHST- 2019/06/01 00:00 [accepted]
PHST- 2019/07/25 06:00 [pubmed]
PHST- 2020/06/09 06:00 [medline]
PHST- 2019/07/25 06:00 [entrez]
PHST- 2019/07/24 00:00 [pmc-release]
AID - EHF212484 [pii]
AID - 10.1002/ehf2.12484 [doi]
PST - ppublish
SO  - ESC Heart Fail. 2019 Oct;6(5):1052-1056. doi: 10.1002/ehf2.12484. Epub 2019 Jul 
      24.