Advanced heart failure clinical stability not improved by liraglutide
medwireNews: The glucagon-like peptide 1 (GLP-1) agonist liraglutide does not improve clinical stability in patients recently hospitalised with advanced heart failure and reduced left ventricular ejection fraction (LVEF), US researchers report.
Kenneth Margulies (Smilow Center for Translational Research, Philadelphia, Pennsylvania) and colleagues make this conclusion “despite prior studies indicating that GLP-1 therapy might ameliorate mechanisms of myocardial insulin resistance reported in patients with severe cardiomyopathies”.
The mulitcentre Functional Impact of GLP-1 for Heart Failure Treatment (FIGHT) study randomly assigned 300 patients (median age 61 years, 79% men) with established heart failure and reduced LVEF (median 25%) to treatment with subcutaneous liraglutide to a target maximal dosage of 1.8 mg/day (n=154) or placebo (n=146) for 180 days.
The primary endpoint was a global rank score in which all patients, regardless of treatment assignment, were ranked across three hierarchical tiers: time to death, with the earliest death being ranked first; followed by time to rehospitalisation for heart failure for those who did not die; and finally time-averaged proportional change in N-terminal pro-B-type natriuretic peptide level from baseline to 180 days for patients who neither died nor were rehospitalised, with higher rank indicating better stability.
As reported in JAMA, there was no significant difference between the two treatment groups in the mean global rank scores, at 146 for the liraglutide group and 156 for the placebo group.
There were also no significant between-group differences in the number of deaths (19 vs 16) or rehospitalisations for heart failure (63 vs 50) with liraglutide versus placebo.
Nor were there any significant differences in the prespecified secondary endpoints, including changes in cardiac structure and function from baseline to 180 days, 6-minute walk test distances, quality of life, emergency department visits or any of the individual primary endpoint components.
Furthermore, there were no significant differences in global rank score or any of the secondary endpoints between liraglutide and placebo in a subgroup analysis of 178 patients with diabetes.
Discussing the reasons for the failure of liraglutide to improve heart failure status in this trial, Margulies et al say it is “possible that patients with advanced heart failure, like those in this trial, are refractory to the otherwise beneficial effects of GLP-1 agonists or are prone to detrimental extracardiac actions of GLP-1, such as impairment of renal function, that are not apparent in other populations.”
By Laura Cowen
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