Liraglutide: Role to Improve Outcomes After Hospitalization for Acute Heart Failure?

Sep 15, 2016
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Authors:
Marguiles KB, Hernandez AF, Redfield MM, et al., on behalf of the NHLBI Heart Failure Clinical Research Network.
Citation:
Effects of Liraglutide on Clinical Stability Among Patients With Advanced Heart Failure and Reduced Ejection Fraction: A Randomized Clinical Trial. JAMA 2016;316:500-508.
Summary By:
Prashant Vaishnava, MD, FACC

Study Questions:

Does therapy with a glucagon-like peptide 1 (GLP-1) agonist improve clinical stability following hospitalization for acute heart failure?

Methods:

FIGHT (Functional Impact of GLP-1 for Heart Failure Treatment) was a phase 2, double-blind, placebo-controlled trial of patients with established heart failure and reduced left ventricular ejection fraction. Eligible patients must have had a recent (within 14 days) hospitalization for an acute heart failure syndrome. Patients were randomized to receive either the GLP-1 agonist liraglutide or placebo as a daily subcutaneous injection. The primary endpoint was a global rank score in which all participants were ranked across three hierarchical tiers: time to death, time to rehospitalization for heart failure, and time-averaged proportional change in N-terminal pro-B-type natriuretic peptide (NT-proBNP) level from baseline to 180 days.

Results:

Compared with placebo, liraglutide had no significant effect on the primary endpoint (mean rank of 146 for the liraglutide group vs. 156 for the placebo group, p = 0.31). There were no significant between-group differences in the number of deaths (19 [12%] in the liraglutide group vs. 16 [11%] in the placebo group; hazard ratio, 1.10; 95% confidence interval [CI], 0.57-2.14; p = 0.78) or rehospitalizations for heart failure (63 [41%] vs. 50 [34%], respectively; hazard ratio, 1.30; 95% CI, 0.89-1.88; p = 0.17).

Conclusions:

Among patients with heart failure with reduced ejection fraction and a recent hospitalization for acute heart failure, the use of liraglutide did not improve post-hospitalization clinical stability.

Perspective:

As the authors acknowledge, “The global rank endpoint...does not allow definitive conclusions about the effect of liraglutide on clinical outcomes.” Nonetheless, the study provides solid evidence that liraglutide does not have favorable effects on time to death or rehospitalization for heart failure in high-risk patients (with a recent hospitalization for an acute heart failure syndrome). The findings from this study do not support the use of liraglutide to improve heart failure status.

Keywords: Biomarkers, Diabetes Mellitus, Glucagon-Like Peptide 1, Heart Failure, Hospitalization, Metabolic Syndrome, Natriuretic Peptide, Brain, Peptide Fragments, Primary Prevention, Stroke Volume, Treatment Failure


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