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FIGHT: GLP-1 agonist did not affect clinical stability after hospitalization in advanced HF
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ORLANDO, Fla. — Liraglutide, a glucagon-like peptide-1 agonist, was not associated with improvement to post-hospitalization clinical stability among patients with advanced HF and reduced ejection fraction, according to results from the FIGHT study.
The double blind trial included 300 high-risk patients with a prior diagnosis of HF and reduced ejection fraction hospitalized for acute HF syndrome despite treatment with guideline-directed medical therapy (median age, 61 years; 21% women, 38% black). More than half of patients (65%) were NYHA Class III and 29% were Class II.
Investigators in the National Heart and Blood Institute’s Heart Failure Clinical Research Network randomly assigned patients at a 1:1 ratio to receive either liraglutide or placebo via daily injection for 1 month. Patients were stratified according to study site and diabetes status.
The primary endpoint consisted of a hierarchical composite rank score, with patients ranked using three tiers: time to death, time to HF hospitalization and time-averaged NT-proBNP trajectory over 180 days of follow-up. A mean rank score was determined for each group, with an anchor value of 150 indicating no effect from treatment.
Secondary endpoints included the individual elements of the primary endpoint at 30, 90 and 180 days; changes to cardiac function and structure as indicated by echocardiogram at 180 days; functional status as indicated by 6-minute walk test results at 30, 90 and 180 days; and symptom changes over 180 days.
The mean global rank score was similar between the groups and near the anchor score in both cases (146 for liraglutide vs. 155 for placebo; P = .309). Patients died in 11% of cases in the placebo group and 12% of the liraglutide group over the course of follow-up; 28% of patients in the placebo group and 34% of patients in the liraglutide group were hospitalized but did not die. Risk for death or HF-related hospitalization was not significantly higher among patients who received liraglutide (HR = 1.296; 95% CI, 0.92-1.83).
Kenneth B. Margulies, MD, of the University of Pennsylvania, Philadelphia, principal investigator for the trial, noted that patients with diabetes who received liraglutide exhibited significantly more weight loss (mean loss, approximately 5 lb), and had better glycemic control than patients with diabetes who received placebo. Incidence of any hyperglycemic events was significantly lower in the liraglutide group (10% vs. 18%; OR = 0.51; P = .048), while there was a trend toward increased risk for worsening renal function in this group (18% vs. 10%; OR = 1.86; P = .073). Rates of all other evaluated adverse events were similar between groups.
“The GLP-1 agonist liraglutide does not improve posthospitaliation clinical stability in patients with advanced HF and reduced EF,” Margulies concluded here. “Larger studies will be needed to establish the safety of liraglutide and other GLP-1 agonists for diabetes management or weight loss in patients with advanced HF. I should emphasize that [results from] this study, which focused on advanced HF, do not preclude a potential beneficial effect for GLP-1 agonists in earlier stages of HF or milder disease.” – by Adam Taliercio
Reference:
Margulies KB, et al. Late-Breaking Clinical Trials 1. Presented at: American Heart Association Scientific Sessions; Nov. 7-11, 2015; Orlando, Fla.
Disclosure: Margulies reports receiving research grants from Celladon Corporation, Innolign Biomedical, Juventis Therapeutics and Thoratec Corporation, and serving as a consultant or on advisory boards for AstraZeneca, Janssen, Merck, Novo Nordisk (unpaid), Pfizer and Ridgetop Research. The other researchers report numerous financial disclosures.
Perspective
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Clyde W. Yancy, MD, MSc, MACP
I think the liraglutide trial is interesting for several reasons. First, it’s yet again proof positive that the Heart Failure Network is working, because we’re able to take very important hypotheses and find a way to efficiently test those hypotheses, generate an answer to a question and either explore it further or move on. That’s brilliant, because the first thing you need for discovery is a process of discovery. I would emphatically state that the Heart Failure Network is our process of discovery for the questions that remain in HF.
Second, we’re recognizing now that we need to spend a lot more time understanding the interface between left ventricle performance and metabolic homeostasis. I am intrigued that a recent antidiabetic or hypoglycemic agent showed for the first time a benefit on CV outcomes.
Is that the direction we need to go? That is, not in the group with established disease that we’re talking about, using an antidiabetic drug to facilitate treatment of symptomatic HF, but rather, are there antidiabetic, hypoglycemic agents that can be deployed during the pre-HF stage that could prevent the progression of HF?
If that’s correct, this opens up a brand new direction, maybe not in the treatment of HF with these agents, but in the prevention of HF, which would actually have more public health and clinical impact than treating advanced disease, as we saw in this trial.
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