CORE-VNS Study Shows Sustained Seizure Reduction With VNS Therapy at 36 Months

Vagus nerve stimulation (VNS) therapy was associated with a 76% median reduction in seizure frequency at 36 months among people with drug-resistant epilepsy (DRE), according to findings from the CORE-VNS study published in Neuromodulation: Technology at the Neural Interface. The prospective, multinational observational study evaluated long-term outcomes associated with adjunctive VNS therapy in children and adults receiving their first VNS implant.¹

Conducted across 61 sites in 16 countries, the newly published analysis included 531 participants receiving their first VNS implant, of whom 426 completed 36 months of follow-up. Among participants with available 36-month seizure data (n = 392), 64% achieved at least a 50% reduction in seizure frequency, and 16% experienced complete seizure freedom. Investigators reported that improvements emerged as early as 3 months after implantation and were sustained throughout the 36-month follow-up period.¹

Beyond seizure frequency, findings showed improvements across several measures of disease burden, including seizure severity, quality of life, and health care resource utilization. At 36 months, 45% of participants with available data reported improved quality of life, while seizure-related hospitalizations decreased by 73% compared with baseline. Investigators also reported no new safety concerns during the study period.¹

“This study provides compelling, real-world evidence supporting the long-term effectiveness and safety of modern VNS Therapy for people living with drug-resistant epilepsy,” Arjune Sen, PhD, FRCP, professor of Global Epilepsy at The University of Oxford, said in a statement.¹ “The CORE-VNS findings underscore the important role VNS Therapy can play in the long-term management of drug-resistant epilepsy and highlight the importance of timely referral to comprehensive epilepsy centers for evaluation once drug resistance has been established.”

Long-Term Seizure and Nonseizure Outcomes

The CORE-VNS analysis found that the proportion of participants achieving higher levels of seizure reduction increased over time. Most participants who responded to VNS therapy maintained or improved their response at subsequent assessments, while regression to lower response categories was uncommon. At 36 months, 28% of participants with available data (108/392) had a 100% reduction in the seizure types present at baseline.¹

Health care utilization also declined during follow-up. The proportion of participants reporting seizure-related emergency department visits decreased from 32% at baseline to 15% at 36 months. Seizure-related hospitalizations declined from 27% to 7% over the same period. These findings suggested that the observed seizure reductions were accompanied by changes in health care utilization.¹

The study also reported reductions in seizure severity and postictal severity across seizure types, alongside changes in rescue medication use and patient-reported quality of life. No new safety concerns were identified.

Additional Context and Implications

The findings extend previously reported CORE-VNS data published in Epilepsia, which showed sustained reductions in generalized tonic-clonic (GTC) seizure frequency through 24 months. In that analysis of 115 participants with generalized seizures at baseline, median GTC seizure frequency declined by 77% at 24 months, and 42.6% reported no GTC seizures during the 3 months preceding the assessment.^2,3

DRE remains a significant treatment challenge for patients who continue to experience seizures despite antiseizure medication. Approximately one-third of people with epilepsy develop drug-resistant disease, according to the study announcement. For these patients, additional treatment approaches, including device-based therapies, may be considered as part of individualized management.

REFERENCES
1. Neuromodulation Publishes Full 36-Month CORE-VNS Results Demonstrating Sustained and Increasing Benefits of LivaNova’s VNS Therapy for Drug-Resistant Epilepsy. LivaNova. News Release. October 23. Accessed October 23, 2026. https://www.businesswire.com/news/home/20261023479534/en/Neuromodulation-Publishes-Full-36-Month-CORE-VNS-Results-Demonstrating-Sustained-and-Increasing-Benefits-of-LivaNovas-VNS-Therapy-for-Drug-Resistant-Epilepsy
2. LivaNova Announces CORE-VNS 24-Month Data Show Adjunctive VNS Therapy is Associated with Substantial Reductions in Generalized Tonic-Clonic Seizures in People with Drug-Resistant Epilepsy. News Release. Published June 5, 2025. Accessed July 8, 2025. https://investor.livanova.com/news-releases/news-release-details/livanova-announces-core-vns-24-month-data-show-adjunctive-vns
3. Suller Marti A, Verner R, Keezer M, et al. Reduction of generalized tonic-clonic seizures following vagus nerve stimulation therapy: CORE-VNS Study 24-month follow-up. Epilepsia. Published online April 1, 2025. doi:10.1111/epi.18371