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J Headache Pain. 2017 Dec;18(1):22. doi: 10.1186/s10194-017-0731-4. Epub 2017 Feb 14.

Effects of non-invasive vagus nerve stimulation on attack frequency over time and expanded response rates in patients with chronic cluster headache: a post hoc analysis of the randomised, controlled PREVA study.

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Department of Headache and Facial Pain, Migraine and Headache Clinic, Ölmühlweg 31, Königstein im Taunus, 61462, Germany.
Headache Research Unit, University Department of Neurology, Centre Hospitalier Régional de la Citadelle, Boulevard du 12ème de Ligne 1, 4000, Liège, Belgium.
electroCore, LLC, 150 Allen Road, Suite 201, Basking Ridge, 07920, NJ, USA.
Department of Neurology, Ludwig-Maximilian University, Marchioninistr 15, Munich, D81377, Germany.



In the PREVention and Acute treatment of chronic cluster headache (PREVA) study, attack frequency reductions from baseline were significantly more pronounced with non-invasive vagus nerve stimulation plus standard of care (nVNS + SoC) than with SoC alone. Given the intensely painful and frequent nature of chronic cluster headache attacks, additional patient-centric outcomes, including the time to and level of therapeutic response, were evaluated in a post hoc analysis of the PREVA study.


After a 2-week baseline phase, 97 patients with chronic cluster headache entered a 4-week randomised phase to receive nVNS + SoC (n = 48) or SoC alone (n = 49). All 92 patients who continued into a 4-week extension phase received nVNS + SoC. Compared with SoC alone, nVNS + SoC led to a significantly lower mean weekly attack frequency by week 2 of the randomised phase; the attack frequency remained significantly lower in the nVNS + SoC group through week 3 of the extension phase (P < 0.02). Attack frequencies in the nVNS + SoC group were significantly lower at all study time points than they were at baseline (P < 0.05). Response rates were significantly greater with nVNS + SoC than with SoC alone when response was defined as attack frequency reductions of ≥25%, ≥50%, and ≥75% from baseline (≥25% and ≥50%, P < 0.001; ≥75%, P = 0.009). The 100% response rate was 8% with nVNS + SoC and 0% with SoC alone.


Prophylactic nVNS led to rapid, significant, and sustained reductions in chronic cluster headache attack frequency within 2 weeks after its addition to SoC and was associated with significantly higher ≥25%, ≥50%, and ≥75% response rates than SoC alone. The rapid decrease in weekly attack frequency justifies a 4-week trial period to identify responders to nVNS, with a high degree of confidence, among patients with chronic cluster headache.


Attack frequency; Chronic cluster headache; Non-invasive vagus nerve stimulation; PREVA; Patient-centric outcomes; Prophylactic treatment; Prophylaxis; Response rate

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