Exenatide regimen does not improve outcomes in patients with out-of-hospital cardiac arrest

NEW ORLEANS — While administering exenatide to patients with out-of-hospital cardiac arrest was safe and feasible, it did not reduce neuron-specific enolase levels or improve clinical outcomes, according to a presentation at the American Heart Association Scientific Sessions.

“Neurological injury remains the leading cause of death in resuscitated out-of-hospital cardiac arrest patients,” Sebastian Wiberg, MD, and colleagues wrote in a simultaneous publication in Circulation. “Currently, the only strategy to mitigate this is targeted temperature management, and additional strategies are needed.”

The randomized, double blind trial enrolled 120 patients aged 18 years or older, who were being treated at two tertiary heart centers for cardiac arrest and had sustained return of spontaneous circulation.

Sebastian Wiberg

Patients eligible for the trial underwent 1:1 randomization to receive either an infusion of 17.4 μg exenatide (Byetta, Eli Lilly), a glucagon-like peptide-1 analog, or placebo over a period of 6 hours and 15 minutes.

The placebo arm was given a solution of 248.5 mL of isotonic sodium chloride and 1.5 mL of 20% human albumin. The active study arm was given the same solution with the addition of 25 μg exenatide. A total of 17.4 μg of exenatide was administered.

The co-primary endpoints of the study were feasibility, defined as initiation of the study drug in > 90% of patients within 4 hours of return of spontaneous circulation; and efficacy, defined as the geometric area under the neuron-specific enolase curve from 24 to 72 hours after admission.

Secondary endpoints of the trial included a composite of death and poor neurological function, defined as a Cerebral Performance Category score between 3 and 5, assessed at 30 days and 180 days.

Within 4 hours of return of spontaneous circulation, the study drug was initiated in 96% of patients, Wiberg, from the department of cardiology, The Heart Centre, Copenhagen University Hospital, Rigshospitalet, Denmark, and colleagues reported.

Eight hours after admission, patients receiving exenatide had a lower blood glucose level than patients assigned placebo (5.8 mmol/L (95% CI, 5.2-6.7) vs. 7.2 mmol/L (95%CI, 6.2-8.7); P < .0001).

There was no significant difference between the groups in the area under the neuron-specific enolase curve (exenatide group, 1,307 μg x 48 hours/L; 95% CI, 884-2,093; placebo group, 1,192 μg x 48 hours/L; 95% CI, 888-1,930; P = .46), according to the researchers.

For the composite endpoint of death and poor neurological function, the groups did not differ at 30 days, 90 days or 180 days (P > .05 for all), Wiberg and colleagues found. Adverse events were rare in both groups and not different between them.

After adjustment for prespecified potential confounders, the point estimate for death favored the exenatide group but was not statistically significant (adjusted HR = 0.62; 95% CI, 0.32-1.2), according to the researchers. –by Dave Quaile

References:

Wiberg, S, et al. Late-Breaking Resuscitation Science Session. Presented at: American Heart Association Scientific Sessions; Nov. 12-16, 2016; New Orleans.

Wiberg S, et al. Circulation. 2016;doi:10.1161/CIRCULATIONAHA.116.024088.

Disclosure: Wiberg reports no relevant financial disclosures.