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Purpose Mutations in ion channels are common among patients with glioblastoma multiforme (GBM) and promote cell migration and invasion. We sought to evaluate the association between the use of specific ion channel blockers such as digoxin, amiodarone, diltiazem and verapamil and GBM risk and survival. Methods We conducted a nested case–control study in a large primary care database from the UK. Cases were defined as all individuals with incident diagnosis of GBM during follow-up. For each case, up to four controls were selected using incidence density sampling. The primary exposure of interest was active treatment with each of the four ion channel blockers. We used conditional logistic regression to estimate odds ratios and 95% confidence interval (CI) for the association between ion channel blocker use and GBM risk. We then performed a Cox regression analysis among those diagnosed with GBM in order to evaluate the association between use of ion channel blockers and overall survival. Both analyses were adjusted to common confounders. Results The study included 1076 cases and 4253 matched controls. There was no statistically significant difference between cases and controls in cardiac and metabolic risk factors. There was no change in GBM risk in active users of ion channel blockers compared with non-users. Among patients with GBM, active users of amiodarone had worse survival compared with never users with an HR of 4.41 (95%CI 1.95–9.96). There was no statistically significant change in survival among diltiazem, verapamil or digoxin users. Conclusion Treatment with specific ion channel blockers was not associated with the risk of GBM but was associated with worse survival in patients with GBM. Copyright © 2016 John Wiley & Sons, Ltd. more...