NECTAR-HF: Vagus nerve stimulation failed to improve cardiac function

BARCELONA, Spain — At 6 months, vagus nerve stimulation with an investigational device did not improve cardiac function in patients with HF, but was associated with significant improvement in quality of life.

“Although robust preclinical data showed the benefit of vagus nerve stimulation, NECTAR-HF … failed to demonstrate a successful clinical translation of vagus nerve stimulation therapy to the primary endpoint of cardiac remodeling,” Faiez Zannad, MD, PhD, from l'Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu, in Vandoeuvre-lès-Nancy, France, said at the ESC Congress, where he presented the 6-month results of the trial.

Researchers enrolled 96 patients at 24 centers in Western Europe with NYHA class II or III HF and an ejection fraction ≤35. All patients were already taking optimal HF therapy. After baseline testing, the patients were randomly assigned to an active group in which the NECTAR-HF System Implant (Boston Scientific) was switched on (n=63) or a sham group in which the device was implanted but remained switched off (n=32). In the active group, the mean stimulation amplitude was 1.24 mA at the start of the study and 1.42 mA at the 3-month follow-up.

The implant was placed in the neck, near the right vagus nerve, and connected to a pulse generator implanted under the skin of the chest.

The trial did not meet the prespecified primary efficacy endpoint of a reduction in LV end-systolic diameter (LVESD) at 6 months as assessed by a blinded echocardiography core laboratory. At 6 months, LVESD was 4.9 cm in the active group vs. 5.1 cm in the sham group. Secondary endpoints, including peak VO₂ (active, 15.8 mL/kg/min; sham, 14.7 mL/kg/min) and NT-proBNP (active, 930 pg/mL; sham, 839 pg/mL), were also similar between the two groups.

However, significant differences between the groups for three subjective quality-of-life endpoints emerged at 6 months. Analyses of the Minnesota Living with Heart Failure Questionnaire (P=.049) and the Short Form-36 physical (P=.02) and mental (P=.24) health surveys demonstrated significant improvement in quality of life with vagus nerve stimulation compared with sham therapy.

In addition, 62% of patients assigned vagus nerve stimulation had an improvement of at least one point from baseline in their NYHA class compared with 45% of patients assigned sham therapy (P=.032).

The 6-month data showed no significant safety concerns and the overall safety profile for this application of vagus nerve stimulation appeared acceptable, Zannad said during a press conference. The overall infection rate was 7.4%.

“NECTAR-HF is the first randomized, sham-controlled trial to evaluate whether right vagus nerve stimulation is safe and might attenuate cardiac remodeling in patients with systolic HF,” Zannad said.

After 6 months of randomization, control patients begin to receive active therapy. All patients will be followed through 18 months for the safety endpoint, according to a company press release.

“Additional clinical research may provide additional insight into the effectiveness of vagus nerve stimulation for HF,” he said, including the appropriate dosing and technique, the effect of baseline medical therapy and a longer period of study. – by Katie Kalvaitis

For more information:

Zannad F. Hot Line I. Cardiovascular Disease: Novel Therapies. Presented at: the European Society of Cardiology Congress; Aug. 30-Sept. 3, 2014; Barcelona, Spain.

Disclosure: The trial was funded by Boston Scientific. Zannad reports receiving honoraria from Air Liquide, Bayer, Biomérieux, Biotronik, Boston Scientific, CVCRx, Janssen Pharmaceuticals, Novartis, Pfizer, Resmed, Roche Diagnostics, Sanofi, Servier, St. Jude Medical and Takeda; speakers fees from Mitsubishi; and stock ownership at CVCT and CardioRenal Diagnostics.