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We investigated the association between VGSC inhibitor use and survival in patients with breast, bowel and prostate cancer.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design<\/jats:title>\n                    <jats:p>Retrospective cohort study.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Setting<\/jats:title>\n                    <jats:p>Individual electronic primary healthcare records extracted from the Clinical Practice Research Datalink.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Participants<\/jats:title>\n                    <jats:p>Records for 132\u2009996 patients with a diagnosis of breast, bowel or prostate cancer.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Outcome measures<\/jats:title>\n                    <jats:p>Adjusted Cox proportional hazards regression was used to analyse cancer-specific survival associated with exposure to VGSC inhibitors. Exposure to non-VGSC-inhibiting antiepileptic medication and other non-VGSC blockers were also considered. Drug exposure was treated as a time-varying covariate to account for immortal time bias.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>During 1\u2009002\u2009225 person-years of follow-up, there were 42\u2009037 cancer-specific deaths. 53\u2009724 (40.4%) patients with cancer had at least one prescription for a VGSC inhibitor of interest. Increased risk of cancer-specific mortality was associated with exposure to this group of drugs (HR 1.59, 95%\u2009CI 1.56 to 1.63, p&lt;0.001). This applied to VGSC-inhibiting tricyclic antidepressants (HR 1.61, 95%\u2009CI 1.50 to 1.65, p&lt;0.001), local anaesthetics (HR 1.49, 95%\u2009CI 1.43 to 1.55, p&lt;0.001) and anticonvulsants (HR 1.40, 95%\u2009CI 1.34 to 1.48, p&lt;0.001) and persisted in sensitivity analyses. In contrast, exposure to VGSC-inhibiting class 1c and 1d antiarrhythmics was associated with significantly improved cancer-specific survival (HR 0.75, 95%\u2009CI 0.64 to 0.88, p&lt;0.001\u2009and HR 0.54, 95%\u2009CI 0.33 to 0.88, p=0.01, respectively).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Association between VGSC inhibitor use and mortality in patients with cancer varies according to indication. Exposure to VGSC-inhibiting antiarrhythmics, but not anticonvulsants, supports findings from preclinical data, with improved survival. However, additional confounding factors may underlie these associations, highlighting the need for further study.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2022-064376","type":"journal-article","created":{"date-parts":[[2023,2,3]],"date-time":"2023-02-03T09:46:27Z","timestamp":1675417587000},"page":"e064376","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":18,"title":["Sodium channel-inhibiting drugs and cancer-specific survival: a population-based study of electronic primary care data"],"prefix":"10.1136","volume":"13","author":[{"given":"Caroline","family":"Fairhurst","sequence":"first","affiliation":[{"name":"Department of Health Sciences, University of York, York, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tim","family":"Doran","sequence":"additional","affiliation":[{"name":"Department of Health Sciences, University of York, York, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabiola","family":"Martin","sequence":"additional","affiliation":[{"name":"School of Public Health, University of Queensland, Brisbane, Queensland, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian","family":"Watt","sequence":"additional","affiliation":[{"name":"Department of Health Sciences, University of York, York, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Bland","sequence":"additional","affiliation":[{"name":"Department of Health Sciences, University of York, York, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6882-3351","authenticated-orcid":false,"given":"William J","family":"Brackenbury","sequence":"additional","affiliation":[{"name":"York Biomedical Research Institute, Department of Biology, University of York, York, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2023,2,3]]},"reference":[{"key":"2025101811070675000_13.2.e064376.1","doi-asserted-by":"publisher","DOI":"10.1007\/s10555-015-9586-9"},{"key":"2025101811070675000_13.2.e064376.2","doi-asserted-by":"publisher","DOI":"10.1038\/s41571-018-0134-8"},{"key":"2025101811070675000_13.2.e064376.3","doi-asserted-by":"publisher","DOI":"10.1007\/112_2020_46"},{"key":"2025101811070675000_13.2.e064376.4","unstructured":"Hille B . 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