PMID- 32164886
OWN - NLM
STAT- MEDLINE
DCOM- 20201209
LR  - 20220513
IS  - 1558-3597 (Electronic)
IS  - 0735-1097 (Linking)
VI  - 75
IP  - 10
DP  - 2020 Mar 17
TI  - Effects of Liraglutide on Cardiovascular Outcomes in Patients With Diabetes With 
      or Without Heart Failure.
PG  - 1128-1141
LID - S0735-1097(20)30248-5 [pii]
LID - 10.1016/j.jacc.2019.12.063 [doi]
AB  - BACKGROUND: More data regarding effects of glucagon-like peptide-1 receptor 
      agonists in patients with type 2 diabetes (T2D) and heart failure (HF) are 
      required. OBJECTIVES: The purpose of this study was to investigate the effects of 
      liraglutide on cardiovascular events and mortality in LEADER (Liraglutide Effect 
      and Action in Diabetes: Evaluation of Cardiovascular Outcome Results) 
      participants, by HF history. METHODS: In the multinational, double-blind, 
      randomized LEADER trial, 9,340 patients with T2D and high cardiovascular risk 
      were assigned 1:1 to liraglutide (1.8 mg daily or maximum tolerated dose up to 
      1.8 mg daily) or placebo plus standard care, and followed for 3.5 to 5 years. New 
      York Heart Association (NYHA) functional class IV HF was an exclusion criterion. 
      The primary composite major adverse cardiovascular events outcome was time to 
      first occurrence of cardiovascular death, nonfatal myocardial infarction, or 
      nonfatal stroke. Post hoc Cox regression analyses of outcomes by baseline HF 
      history were conducted. RESULTS: At baseline, 18% of patients had a history of 
      NYHA functional class I to III HF (liraglutide: n = 835 of 4,668; placebo: 
      n = 832 of 4,672). Effects of liraglutide versus placebo on major adverse 
      cardiovascular events were consistent in patients with (hazard ratio [HR]: 0.81 
      [95% confidence interval (CI): 0.65 to 1.02]) and without (HR: 0.88 [95% CI: 0.78 
      to 1.00]) a history of HF (p interaction = 0.53). In both subgroups, fewer deaths 
      were observed with liraglutide (HR: 0.89 [95% CI: 0.70 to 1.14] with HF; HR: 0.83 
      [95% CI: 0.70 to 0.97] without HF; p interaction = 0.63) versus placebo. No 
      increased risk of HF hospitalization was observed with liraglutide, regardless of 
      HF history (HR: 0.98 [95% CI: 0.75 to 1.28] with HF; HR: 0.78 [95% CI: 0.61 to 
      1.00] without HF; p interaction = 0.22). Effects of liraglutide on the composite 
      of HF hospitalization or cardiovascular death were consistent in patients with 
      (HR: 0.92 [95% CI: 0.74 to 1.15]) and without (HR: 0.77 [95% CI: 0.65 to 0.91]) a 
      history of HF (p interaction = 0.19). CONCLUSIONS: Based on these findings, 
      liraglutide should be considered suitable for patients with T2D with or without a 
      history of NYHA functional class I to III HF. (Liraglutide Effect and Action in 
      Diabetes: Evaluation of Cardiovascular Outcome Results [LEADER]; NCT01179048).
CI  - Copyright (c) 2020. Published by Elsevier Inc.
FAU - Marso, Steven P
AU  - Marso SP
AD  - Midwest Heart and Vascular Institute, HCA Midwest Health, Overland Park, Kansas. 
      Electronic address: Steve.Marso@HCAHealthcare.com.
FAU - Baeres, Florian M M
AU  - Baeres FMM
AD  - Novo Nordisk A/S, Soborg, Denmark.
FAU - Bain, Stephen C
AU  - Bain SC
AD  - Swansea University Medical School, Swansea, Wales, United Kingdom.
FAU - Goldman, Bryan
AU  - Goldman B
AD  - Novo Nordisk A/S, Soborg, Denmark.
FAU - Husain, Mansoor
AU  - Husain M
AD  - Ted Rogers Centre for Heart Research, Toronto General Hospital Research 
      Institute, Toronto, Ontario, Canada.
FAU - Nauck, Michael A
AU  - Nauck MA
AD  - Diabetes Center Bochum-Hattingen, St. Josef-Hospital (Ruhr University), Bochum, 
      Germany.
FAU - Poulter, Neil R
AU  - Poulter NR
AD  - Faculty of Medicine, School of Public Health, Imperial College London, London, 
      United Kingdom.
FAU - Pratley, Richard E
AU  - Pratley RE
AD  - AdventHealth Translational Research Institute for Metabolism and Diabetes, 
      Orlando, Florida.
FAU - Thomsen, Anne Bloch
AU  - Thomsen AB
AD  - Novo Nordisk A/S, Soborg, Denmark.
FAU - Buse, John B
AU  - Buse JB
AD  - University of North Carolina School of Medicine, Chapel Hill, North Carolina.
CN  - LEADER Trial Investigators
LA  - eng
SI  - ClinicalTrials.gov/NCT01179048
GR  - UL1 TR002489/TR/NCATS NIH HHS/United States
GR  - UC4 DK108612/DK/NIDDK NIH HHS/United States
GR  - U54 DK118612/DK/NIDDK NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Am Coll Cardiol
JT  - Journal of the American College of Cardiology
JID - 8301365
RN  - 0 (Hypoglycemic Agents)
RN  - 839I73S42A (Liraglutide)
SB  - IM
CIN - J Am Coll Cardiol. 2020 Mar 17;75(10):1142-1144. PMID: 32164887
MH  - Aged
MH  - Cardiovascular Diseases/drug therapy/mortality
MH  - Death
MH  - Diabetes Mellitus, Type 2/*drug therapy/*mortality
MH  - Double-Blind Method
MH  - Female
MH  - Heart Failure/*drug therapy/*mortality
MH  - Hospitalization/trends
MH  - Humans
MH  - Hypoglycemic Agents/*therapeutic use
MH  - Internationality
MH  - Liraglutide/*therapeutic use
MH  - Male
MH  - Middle Aged
MH  - Treatment Outcome
OTO - NOTNLM
OT  - GLP-1 receptor agonist
OT  - heart failure
OT  - liraglutide
OT  - major adverse cardiovascular events
OT  - mortality
OT  - type 2 diabetes
EDAT- 2020/03/14 06:00
MHDA- 2020/12/15 06:00
CRDT- 2020/03/14 06:00
PHST- 2019/06/25 00:00 [received]
PHST- 2019/12/11 00:00 [revised]
PHST- 2019/12/17 00:00 [accepted]
PHST- 2020/03/14 06:00 [entrez]
PHST- 2020/03/14 06:00 [pubmed]
PHST- 2020/12/15 06:00 [medline]
AID - S0735-1097(20)30248-5 [pii]
AID - 10.1016/j.jacc.2019.12.063 [doi]
PST - ppublish
SO  - J Am Coll Cardiol. 2020 Mar 17;75(10):1128-1141. doi: 10.1016/j.jacc.2019.12.063.