ENCORE: Vagal nerve stimulation safe, well tolerated, results maintained at 12 months

NATIONAL HARBOR, Md. — The ENCORE study, which extends follow-up from the ANTHEM-HF study by 6 months, demonstrated that vagal nerve stimulation was safe and well tolerated on both the left and right vagal nerves of patients with HF with reduced ejection fraction, and benefits observed with vagal nerve stimulation at 6 months were maintained at 12 months according to data presented at the Heart Failure Society of America Annual Scientific Meeting.

In the ANTHEM-HF trial, 60 patients with HF with reduced left ventricular ejection fraction (≤ 40%) and NYHA class II to III HF were randomly assigned to receive a vagus nerve stimulation device (VNS Therapy System, Cyberonics) implanted on the left or right side of the vagus nerve.

ENCORE was designed as a follow-up study to ANTHEM-AF. Seven of 10 investigators from ANTHEM-HF were involved. The mean age of patients was 52 years and 86% were men. These patient characteristics were similar to the ANTHEM-HF study, but patients in the ENCORE trial were younger, according to Anand. All patients were taking beta-blockers and none had implantable cardioverter defibrillators or cardiac resynchronization therapy devices.

Inder S. Anand

Patients were followed for an additional 6 months “to confirm whether the effects of electrical stimulation of the right and left vagus nerves in patients with chronic HF were maintained at 1 year,” Inder S. Anand, MD, DPhil, from the University of Minnesota Medical School, Minneapolis, said during a presentation.

During follow-up, tolerance for vagal nerve stimulation increased, Anand said. No serious device-related adverse events occurred. Seven serious adverse events were reported; none were related to the device or therapy, Anand said. No patients withdrew from the study due to system malfunction or requested discontinuation of therapy.

“ENCORE demonstrates that vagal nerve stimulation is feasible and well tolerated over an extended period of time,” Anand said.

While discussing the results, Mandeep R. Mehra, MD, medical director of the Brigham and Women’s Hospital Heart and Vascular Center, who was not involved with the ENCORE trial, noted that adverse events were improved in the ENCORE follow-up study compared with in the ANTHEM-HF trial.

“If you look at the first 6 months, there were significant symptoms. Thirteen patients of the 60-patient cohort had mild symptoms of cough, 19 had dysphonia, eight had oropharyngeal pain,” he said. “Two-thirds of the initial patients had some side effects from vagal nerve stimulation, which curiously improved over time.”

Mehra also said the need to determine a dose for vagal nerve stimulation is “critical.”

“It is imperative that a bio signature for a direct mechanistic response to vagal nerve stimulation be developed, because one has to ascertain responder status from nonresponder status and cannot just look at surrogates in open-label trials like this.” – by Julia Ernst, MS

Reference:

Anand IS, et al. Late-Breaking Clinical Trials. Presented at: Heart Failure Society of America Annual Scientific Meeting; Sept. 26-29, 2015; National Harbor, Md.

Disclosure: Anand reports receiving a research grant from Cyberonics, which sponsored the trial. Mehra reports no relevant financial disclosures.