LivaNova Reports 36-Month CORE-VNS Study Results Showing Sustained Seizure Reduction and Improved Quality of Life in Drug-Resistant Epilepsy
LivaNova PLC, a medical technology company specializing in therapies for neurological and cardiac conditions, has announced the publication of the complete 36-month results from the CORE-VNS study in the journal Neuromodulation: Technology at the Neural Interface. The study represents the first long-term effectiveness evaluation of contemporary VNS Therapy™ devices in people living with drug-resistant epilepsy (DRE), providing important evidence on seizure outcomes, patient quality of life, safety, and healthcare resource utilization.
The publication, titled “CORE-VNS Seizure and Non-Seizure 36 Month Outcomes in People with Drug-resistant Epilepsy,” presents findings from the international CORE-VNS cohort. Conducted across 61 clinical sites in 16 countries, the study evaluated outcomes among children and adults receiving adjunctive vagus nerve stimulation (VNS) Therapy for drug-resistant epilepsy.
The 36-month findings showed sustained improvements in seizure control, with a median reduction in seizure frequency of 76% among participants with available follow-up data. At the three-year assessment, 64% of participants achieved at least a 50% reduction in seizure frequency, including nearly half who experienced an 80% or greater reduction.
The study also reported improvements extending beyond seizure frequency. These included complete seizure freedom in a subset of participants, improved quality of life, reduced seizure severity, changes in rescue medication use, and fewer seizure-related hospitalizations and emergency department visits. Investigators reported that clinical benefits emerged as early as three months after implantation and were maintained or improved for many participants throughout the follow-up period.
According to LivaNova, the findings provide additional evidence supporting the role of contemporary VNS Therapy in the long-term management of people whose epilepsy remains uncontrolled despite medication.
Addressing the Challenges of Drug-Resistant Epilepsy
Epilepsy is a chronic neurological disorder characterized by a predisposition to recurrent seizures. It affects more than 50 million people worldwide and can have a substantial impact on daily activities, independence, education, employment, and overall quality of life.
Although anti-seizure medications are the primary treatment for many people with epilepsy, approximately one-third of patients continue to experience seizures despite treatment. These patients may develop drug-resistant epilepsy, a condition associated with ongoing seizure-related risks and significant physical, psychological, and social challenges.
Uncontrolled seizures can increase the risk of injuries, emergency medical care, hospitalization, and complications associated with prolonged or recurrent seizure activity. Patients may also experience post-ictal symptoms, the period following a seizure that can involve confusion, fatigue, headaches, or other neurological and physical effects.
For people with DRE, finding an effective treatment strategy can be difficult. Treatment decisions may involve reassessing medication regimens, evaluating eligibility for epilepsy surgery, or considering neuromodulation approaches designed to reduce seizure frequency and severity.
Clinical practice guidelines recommend referral to specialized epilepsy centers once drug resistance has been established. These centers can provide comprehensive assessment and determine whether patients may benefit from advanced treatment options. However, some patients experience considerable delays before receiving specialist evaluation.
The CORE-VNS study provides long-term evidence on one such treatment option: vagus nerve stimulation therapy, which is used alongside existing anti-seizure medications to help manage seizures in eligible patients.
Overview of the CORE-VNS Study
CORE-VNS was an international study designed to evaluate the long-term effectiveness and safety of contemporary VNS Therapy devices in people with drug-resistant epilepsy.
The study involved 61 sites across 16 countries, allowing investigators to assess treatment outcomes in a geographically diverse clinical population. The published analysis included 531 participants receiving their first VNS Therapy implant. These participants were drawn from the broader study population of more than 800 individuals.
Of the 531 participants included in the published analysis, 426 completed 36 months of follow-up, representing an 80% retention rate.
The study evaluated outcomes in both children and adults, examining changes in seizure frequency and other clinically relevant measures over three years. In addition to seizure reduction, the investigators assessed seizure freedom, seizure severity, post-ictal severity, quality of life, rescue medication use, and healthcare resource utilization.
The long-term follow-up period is particularly relevant because treatment effectiveness may change over time. A therapy that initially produces a modest reduction in seizures may provide greater benefits with continued use, while other patients may experience changes in response or tolerability.
The CORE-VNS findings indicate that many participants maintained or improved their responses over the three-year period. The study also found that progression into lower response categories was uncommon among participants who had previously responded to VNS Therapy.
These observations provide insight into how treatment outcomes developed over time rather than relying solely on a single assessment after implantation.
Seizure Frequency Reduced by 76% at 36 Months
One of the principal findings from the published analysis was a 76% median reduction in seizure frequency from baseline among participants with available 36-month follow-up data.
This result indicates that the typical participant in the analyzed population experienced a substantial decrease in the frequency of seizures over the study period.
At the 36-month assessment, 64% of participants achieved at least a 50% reduction in seizure frequency. This level of improvement is commonly used in epilepsy research to identify treatment responders.
Nearly half of the participants experienced an 80% or greater reduction in seizures, suggesting that a substantial proportion achieved reductions exceeding the conventional responder threshold.
The findings also indicated that benefits could emerge relatively early. Meaningful improvements were observed as soon as three months after implantation, with effectiveness generally sustained throughout the subsequent follow-up period.
Importantly, the study did not show that all participants achieved the same degree of improvement. Treatment responses varied, as would be expected in a population with different seizure types, disease histories, and clinical characteristics.
Nevertheless, the overall findings suggest that VNS Therapy may provide sustained seizure reduction for many people with drug-resistant epilepsy when used as an adjunct to existing treatment.
Seizure Freedom and Reduction in Baseline Seizure Types
Beyond reductions in seizure frequency, the study evaluated whether participants achieved complete seizure freedom or experienced elimination of the seizure types present at baseline.
At 36 months, 16% of participants achieved complete seizure freedom, corresponding to 64 of 392 participants. The reported 95% confidence interval was 13.3%–19.7%.
Seizure freedom is an important outcome for patients and caregivers because even infrequent seizures can affect safety, independence, and daily functioning. However, the reported result applies to the subgroup with the relevant available outcome data and should not be interpreted as a guarantee that VNS Therapy will eliminate seizures for an individual patient.
The analysis also found that 28% of participants, or 108 of 392, experienced a 100% reduction in the seizure types present at baseline. The 95% confidence interval for this outcome was 23.9%–31.5%.
This measure differs from overall seizure freedom because it refers to the disappearance of the seizure types identified at baseline. It provides additional information about how treatment may change the pattern of seizure activity experienced by individual patients.
Investigators reported that the proportion of participants achieving seizure freedom increased steadily throughout the study. Among those who responded to VNS Therapy, most maintained or improved their outcomes at subsequent assessments.
The durability of these responses is an important aspect of the findings, as long-term seizure management often requires therapies that provide sustained benefits rather than short-term improvements alone.
Improvements in Quality of Life and Seizure Severity
The effects of epilepsy extend beyond the number of seizures a person experiences. The condition can influence emotional well-being, social participation, physical functioning, and the ability to engage in everyday activities.
For this reason, the CORE-VNS analysis also examined quality of life and measures of seizure severity.
At 36 months, 45% of participants with available quality-of-life data reported an improvement. This represented 174 of 391 participants.
The finding suggests that a substantial proportion of participants perceived benefits in aspects of their lives beyond seizure frequency. Such improvements may be important for patients and caregivers who must manage the unpredictable nature of drug-resistant epilepsy.
The study also reported significant reductions in seizure severity and post-ictal severity across all seizure types.
Seizure severity encompasses the impact and characteristics of seizure episodes, while post-ictal severity relates to the symptoms and functional effects that occur after a seizure. Reductions in these measures may be clinically relevant even when seizures do not disappear entirely.
For patients, less severe seizure episodes or shorter and less disruptive recovery periods may help improve daily functioning. These outcomes can also affect caregiver burden and the amount of assistance patients need following seizures.
Although the findings support improvements across multiple measures, individual experiences can vary. The study results describe outcomes observed across the analyzed population rather than predicting the response of every person receiving VNS Therapy.
Reduced Emergency Department Visits and Hospitalizations
Another important finding was the reduction in seizure-related healthcare resource utilization over the 36-month study period.
At baseline, 32% of participants reported seizure-related emergency department visits. By the 36-month assessment, this proportion had decreased to 15%.
The analysis also showed a substantial decline in seizure-related hospitalizations. At baseline, 27% of participants reported seizure-related hospitalizations, compared with 7% at 36 months.
This represented a 73% reduction in the proportion of participants reporting seizure-related hospitalizations compared with baseline.
Fewer emergency department visits and hospital admissions may indicate improvements in seizure management and a reduced need for urgent medical intervention. Such changes can be important for patients, caregivers, healthcare providers, and healthcare systems.
Hospital visits can disrupt daily life, create additional financial and logistical burdens, and expose patients to further stress. A reduction in seizure-related acute care may therefore represent a meaningful benefit when considered alongside seizure frequency and severity.
However, the reported changes reflect outcomes observed during the study and do not independently establish that VNS Therapy was the sole cause of the reductions. Further interpretation should account for the study design, changes in patient management, and other factors that may influence healthcare utilization over time.
Long-Term Safety Findings
Safety was another important component of the CORE-VNS evaluation. The published analysis reported no new safety concerns during the 36-month follow-up period.
Long-term safety data are particularly valuable for treatments intended to manage chronic neurological conditions. Patients with drug-resistant epilepsy may require treatment over many years, making it important to understand both the durability of clinical benefits and the safety profile associated with continued use.
The absence of new safety concerns in the reported analysis provides additional information about the use of contemporary VNS Therapy devices in the evaluated population.
Nevertheless, the findings should be interpreted within the context of the study population and follow-up period. Continued clinical monitoring remains important for patients receiving VNS Therapy, and treatment decisions should be based on individual medical circumstances and specialist assessment.
The study’s inclusion of both children and adults also provides information about outcomes across a broad patient population, although individual eligibility and treatment considerations may differ according to age, seizure characteristics, and medical history.
Expert Commentary Highlights the Importance of Early Referral
Arjune Sen, Professor of Global Epilepsy at the University of Oxford, Consultant Neurologist at Oxford University Hospitals NHS Foundation Trust, and coordinating investigator for CORE-VNS, emphasized the significance of the long-term findings.
“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,” Sen said.
He noted that meaningful clinical benefits were observed as early as three months after implantation and continued throughout the study period. He also highlighted the improvements in healthcare utilization and reductions in seizure severity.
Sen said the findings reinforce the role VNS Therapy can play in the long-term management of drug-resistant epilepsy. He also emphasized the importance of timely referral to comprehensive epilepsy centers once drug resistance has been established.
Early referral can help ensure that patients receive a thorough evaluation of available treatment options, including medication adjustments, surgical assessment, and neuromodulation therapies where appropriate.
The study findings may therefore support greater awareness of the need to evaluate advanced treatment options when seizures remain uncontrolled despite appropriate medication trials.
LivaNova Highlights the Broader Clinical Significance
Stephanie Bolton, President of Global Epilepsy at LivaNova, said the publication demonstrates benefits across multiple measures that matter to patients, caregivers, and healthcare systems.
“The findings published in Neuromodulation demonstrate not only a 76% median reduction in seizure frequency at three years but also meaningful benefits across multiple measures important to patients, caregivers, and healthcare systems,” Bolton said.
She added that the early emergence and continued improvement of treatment benefits were particularly encouraging, reinforcing the potential role of VNS Therapy in long-term epilepsy management.
LivaNova’s announcement positions the CORE-VNS results as evidence supporting contemporary VNS Therapy devices for patients whose epilepsy remains inadequately controlled with medication.
The study’s focus on long-term outcomes is especially relevant in a chronic condition where treatment goals often extend beyond reducing seizure counts. Improvements in quality of life, seizure severity, and healthcare utilization can also influence how patients experience the disease and manage their daily activities.
Implications for the Management of Drug-Resistant Epilepsy
The complete 36-month CORE-VNS results provide a broad assessment of outcomes associated with contemporary VNS Therapy in people with drug-resistant epilepsy.
The study reported a 76% median reduction in seizure frequency, complete seizure freedom in 16% of participants with available data, and a 100% reduction in baseline seizure types in 28%. Nearly half of the participants with available quality-of-life data reported improvements, while seizure-related hospitalizations declined substantially compared with baseline.
The findings also indicated that clinical benefits could emerge within three months of implantation and remain durable through three years of follow-up. No new safety concerns were identified in the published analysis.
Despite these encouraging results, VNS Therapy is not a guaranteed cure for epilepsy, and responses vary between individuals. The reported findings should also be considered in light of the study design, the number of participants with available data for each outcome, and the possibility that other factors contributed to changes observed during follow-up.
For healthcare professionals, the findings reinforce the importance of evaluating people with persistent seizures for advanced treatment options rather than allowing prolonged delays after drug resistance becomes apparent.
For patients and caregivers, the results offer additional information about the potential long-term benefits of VNS Therapy, including outcomes that extend beyond seizure frequency alone.
As epilepsy care continues to evolve, long-term clinical evidence will remain important for guiding treatment decisions and helping patients access appropriate therapies. The publication of the CORE-VNS findings in Neuromodulation: Technology at the Neural Interface adds to the evidence base supporting the role of VNS Therapy as an adjunctive option in the management of drug-resistant epilepsy.
About CORE-VNS
CORE-VNS is a real-world, long-term, open-label study focused on the outcomes of VNS Therapy™ in people diagnosed with drug-resistant epilepsy (DRE). Enrolling more than 800 people from 61 sites worldwide, the study is the most comprehensive assessment of the effectiveness of VNS Therapy to date and provides modern insights into the global use of VNS Therapy in the management and control of seizures. As an observational study, outcomes reflect real-world clinical practice and should be interpreted within the context of the study design.
Adverse events in the CORE-VNS study were typical of those reported in the product labeling and experienced following placement of a VNS Therapy device. The most commonly reported (>5%) adverse events overall included respiratory, thoracic, and mediastinal disorders (dysphonia, dyspnea, cough) and general disorders/administration site conditions. See important safety information at VNSTherapy.com/safety.
About VNS Therapy™ for Epilepsy
VNS Therapy™ is approved and clinically proven safe and effective as an adjunctive therapy to reduce the frequency of seizures in adults and children with Drug-Resistant Epilepsy and focal onset seizures. It is a unique treatment approach developed for people with Drug-Resistant Epilepsy—a condition that affects approximately one in three people with epilepsy.
Unlike some other surgical treatment options for people with Drug-Resistant Epilepsy, VNS Therapy implantation generally involves a day case procedure, with many completed in outpatient settings, and does not require penetration of the skull. Outside the United States, the VNS Therapy indications for use may vary. For more information, including indications, contraindications, warnings, and precautions, please visit VNSTherapy.com/safety.
About LivaNova
LivaNova PLC is a global medical technology company built on nearly five decades of experience and a vision to change the trajectory of lives for a new day. Through ingenious medical solutions in select neurological and cardiac conditions, LivaNova strives to ignite patient turnarounds. With its registered office in the United Kingdom, approximately 3,300 employees, and a presence in more than 100 countries, LivaNova serves patients, healthcare professionals, and healthcare systems worldwide.