INOVATE-HF: Vagal nerve stimulation does not improve outcomes in patients with HF

CHICAGO — Patients with chronic HF who were treated with a vagal nerve stimulation system did not experience a reduction in death from any cause or HF events, according to data presented at the American College of Cardiology Scientific Session.

Perspective from Biykem Bozkurt, MD, FACC

Michael R. Gold, MD, PhD, Michael E. Assey Professor of Medicine at the Medical University of South Carolina in Charleston and president-elect of the Heart Rhythm Society, and colleagues randomly assigned 707 patients with chronic HF, ejection fraction 40% and NYHA class III symptoms to receive vagal nerve stimulation with the CardioFit system (BioControl Medical) or continued medical therapy. The system provides autonomic modulation to increase parasympathetic tone and decrease sympathetic tone.

Michael R. Gold

The primary outcome was all-cause mortality or first event indicating worsening of HF. Mean follow-up was 16 months.

The rate of the primary outcome was numerically higher in the vagal nerve stimulation group than in the control group (30.3% vs. 25.8%; HR = 1.14; 95% CI, 0.86-1.53), Randall C. Starling, MD, MPH, professor of medicine, section of heart failure and cardiac transplant medicine, medical director of the Kaufman Center for Heart Failure, staff cardiologist in the Robert and Suzanne Tomsich Department of Cardiovascular Medicine and vice chairman of Cardiovascular Medicine Operations at Cleveland Clinic, said during a press conference. Starling noted that the estimated annual rate of the primary outcome was 22.1% in the stimulation group and 19.7% in the control group.

Randall C. Starling

Estimated annual mortality rates during the study were similar between the groups (stimulation group, 9.3%; control group, 7.1%; P = .19), according to the researchers.

Compared with controls, the stimulation group showed improvement in NYHA class, 6-minute walk distance and quality of life as assessed by the Kansas City Cardiomyopathy Questionnaire (P < .05 for all).

“Vagal nerve stimulation ... has an acceptable safety profile and it’s well-tolerated long-term,” Starling said. “The therapy did not reduce the incidence of [HF] events or all-cause mortality among patients with class III [HF] and reduced [EF]. We did, ironically, see positive trends in HF class, exercise capacity and Kansas City quality of life. [The study] was not blinded, so that could certainly introduce bias.”

In an interview with Cardiology Today, Mary Norine Walsh, MD, FACC, medical director of HF and cardiac transplantation and director of nuclear cardiology at St. Vincent Heart Center, Indianapolis, and president-elect of the ACC, who was an investigator on the trial, said “it was disappointing as an investigator to get the news that the study was stopped early.”

Mary Norine Walsh

She said that the researchers “had high hopes for vagal nerve stimulation with this therapy. ... It was a very well-done protocol. I would characterize it as another disappointment in the search for HF therapy. ... I don’t think there’s anything about the trial that makes the results inaccurate.” – by Erik Swain

Reference s :

Gold MR, et al. Late-Breaking Clinical Trials V. Presented at: American College of Cardiology Scientific Session; April 2-4, 2016; Chicago.

Gold MR, et al. J Am Coll Cardiol. 2016;doi:10.1016/j.jacc.2016.03.525.

Disclosure: The study was funded by BioControl Medical. Gold and Starling report receiving research grants from and consulting for BioControl Medical. Walsh reports no relevant financial disclosures. See the full study for a list of the other researchers’ relevant financial disclosures.

Perspective

Biykem Bozkurt, MD, FACC

We were expecting favorable results, and the lack of them are a concern. The sample size is one possible explanation for why we didn’t see any benefit. A second is that it is important to find out whether there were any alterations in the heart rate, and whether the patient selection should have identified more individuals who may have benefited from vagal stimulation, for example sicker patients with tachycardia, who were not enrolled in this trial. Another component is that any new treatment will require optimization of background therapy. Compared with what we saw in older studies, we now have optimal ACE inhibitor use and optimal beta-blocker use. Longer-term beta-blocker use will create blunting of the sympathetic tone in the autonomic nervous system, and may create a little leeway for those individuals who may benefit. It will have to be validated whether the device upregulated the parasympathetic system and downregulated the sympathetic system. It must be documented what kind of parasympathetic dominance was created throughout the day, and whether that was appropriate for the patients. I think adjustments are key with this kind of technology. We need an approach to better individualize these therapies in a much larger sample size, perhaps expanding the trial population to include a wider portfolio of heart rates.

Biykem Bozkurt, MD, FACC

Professor of Medicine, Section of Cardiology

Winters Center for Heart Failure Research

Baylor College of Medicine

Cardiology Section Chief

Medical Care Line Executive

Michael E. DeBakey Veterans Affairs Medical Center, Houston

Disclosures: Bozkurt reports no relevant financial disclosures.