Effects of liraglutide on cardiovascular outcomes in patients with diabetes with or without heart failure
OA Location
Author(s)
Type
Journal Article
Abstract
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).
Date Issued
2020-03-17
Date Acceptance
2019-12-17
Citation
Journal of the American College of Cardiology, 2020, 75 (10), pp.1128-1141
ISSN
0735-1097
Publisher
Elsevier
Start Page
1128
End Page
1141
Journal / Book Title
Journal of the American College of Cardiology
Volume
75
Issue
10
Copyright Statement
© 2020 Published by Elsevier on behalf of the American College of Cardiology Foundation.
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/32164886
PII: S0735-1097(20)30248-5
Subjects
GLP-1 receptor agonist
heart failure
liraglutide
major adverse cardiovascular events
mortality
type 2 diabetes
Aged
Cardiovascular Diseases
Death
Diabetes Mellitus, Type 2
Double-Blind Method
Female
Heart Failure
Hospitalization
Humans
Hypoglycemic Agents
Internationality
Liraglutide
Male
Middle Aged
Treatment Outcome
Publication Status
Published
Coverage Spatial
United States
Date Publish Online
2020-03-09