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.
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。