PDF(Pubmed)
Abstract：
Antiepileptic and antiarrhythmic drugs inhibit voltage-gated sodium (Na+) channels (VGSCs), and preclinical studies show that these medications reduce tumour growth, invasion and metastasis. We investigated the association between VGSC inhibitor use and survival in patients with breast, bowel and prostate cancer.
Retrospective cohort study.
Individual electronic primary healthcare records extracted from the Clinical Practice Research Datalink.
Records for 132 996 patients with a diagnosis of breast, bowel or prostate cancer.
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.
During 1 002 225 person-years of follow-up, there were 42 037 cancer-specific deaths. 53 724 (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% CI 1.56 to 1.63, p<0.001). This applied to VGSC-inhibiting tricyclic antidepressants (HR 1.61, 95% CI 1.50 to 1.65, p<0.001), local anaesthetics (HR 1.49, 95% CI 1.43 to 1.55, p<0.001) and anticonvulsants (HR 1.40, 95% CI 1.34 to 1.48, p<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% CI 0.64 to 0.88, p<0.001 and HR 0.54, 95% CI 0.33 to 0.88, p=0.01, respectively).
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.
Retrospective cohort study.
Individual electronic primary healthcare records extracted from the Clinical Practice Research Datalink.
Records for 132 996 patients with a diagnosis of breast, bowel or prostate cancer.
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.
During 1 002 225 person-years of follow-up, there were 42 037 cancer-specific deaths. 53 724 (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% CI 1.56 to 1.63, p<0.001). This applied to VGSC-inhibiting tricyclic antidepressants (HR 1.61, 95% CI 1.50 to 1.65, p<0.001), local anaesthetics (HR 1.49, 95% CI 1.43 to 1.55, p<0.001) and anticonvulsants (HR 1.40, 95% CI 1.34 to 1.48, p<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% CI 0.64 to 0.88, p<0.001 and HR 0.54, 95% CI 0.33 to 0.88, p=0.01, respectively).
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.
摘要：
目的：抗癫痫和抗心律失常药物抑制电压门控钠（Na+）通道（VGSCs），临床前研究表明，这些药物可以减少肿瘤的生长，侵袭和转移。我们调查了乳腺癌患者使用VGSC抑制剂与生存率之间的关系。肠癌和前列腺癌.
方法：回顾性队列研究。
方法：从临床实践研究数据链中提取的个人电子初级医疗记录。
方法：记录了132996例诊断为乳腺的患者，肠癌或前列腺癌。
方法：使用校正Cox比例风险回归分析与暴露于VGSC抑制剂相关的癌症特异性生存率。还考虑暴露于非VGSC抑制性抗癫痫药物和其他非VGSC阻断剂。药物暴露被视为时变协变量，以解释不朽的时间偏差。
结果：在1002225人年的随访中，有42037例癌症特异性死亡。53724名(40.4%)癌症患者有至少一个目的VGSC抑制剂的处方。癌症特异性死亡率的增加与暴露于该组药物相关（HR1.59，95％CI1.56至1.63，p<0.001）。这适用于抑制VGSC的三环抗抑郁药（HR1.61，95％CI1.50至1.65，p<0.001），局部麻醉药(HR1.49,95%CI1.43~1.55,p<0.001)和抗惊厥药(HR1.40,95%CI1.34~1.48,p<0.001)在敏感性分析中持续存在.相比之下,暴露于VGSC抑制性1c类和1d类抗心律失常药物与显著提高癌症特异性生存率相关(分别为HR0.75,95%CI0.64~0.88,p<0.001和HR0.54,95%CI0.33~0.88,p=0.01).
结论：VGSC抑制剂的使用与癌症患者死亡率之间的关联因适应症而异。暴露于抑制VGSC的抗心律失常药物，但不是抗惊厥药,支持来自临床前数据的发现，改善生存。然而,其他混杂因素可能是这些关联的基础，强调需要进一步研究。
方法：回顾性队列研究。
方法：从临床实践研究数据链中提取的个人电子初级医疗记录。
方法：记录了132996例诊断为乳腺的患者，肠癌或前列腺癌。
方法：使用校正Cox比例风险回归分析与暴露于VGSC抑制剂相关的癌症特异性生存率。还考虑暴露于非VGSC抑制性抗癫痫药物和其他非VGSC阻断剂。药物暴露被视为时变协变量，以解释不朽的时间偏差。
结果：在1002225人年的随访中，有42037例癌症特异性死亡。53724名(40.4%)癌症患者有至少一个目的VGSC抑制剂的处方。癌症特异性死亡率的增加与暴露于该组药物相关（HR1.59，95％CI1.56至1.63，p<0.001）。这适用于抑制VGSC的三环抗抑郁药（HR1.61，95％CI1.50至1.65，p<0.001），局部麻醉药(HR1.49,95%CI1.43~1.55,p<0.001)和抗惊厥药(HR1.40,95%CI1.34~1.48,p<0.001)在敏感性分析中持续存在.相比之下,暴露于VGSC抑制性1c类和1d类抗心律失常药物与显著提高癌症特异性生存率相关(分别为HR0.75,95%CI0.64~0.88,p<0.001和HR0.54,95%CI0.33~0.88,p=0.01).
结论：VGSC抑制剂的使用与癌症患者死亡率之间的关联因适应症而异。暴露于抑制VGSC的抗心律失常药物，但不是抗惊厥药,支持来自临床前数据的发现，改善生存。然而,其他混杂因素可能是这些关联的基础，强调需要进一步研究。
