Increased risk of metastasis in patients with incidental use of renin-angiotensin system inhibitors: a retrospective analysis for multiple types of cancer based on electronic medical records
Increased risk of metastasis in patients with incidental use of renin-angiotensin system inhibitors: a retrospective analysis for multiple types of cancer based on electronic medical records
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DOI：
10.1038/s41440-022-01038-4
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发表时间：
2022-09
影响因子：
5.4
通讯作者：
Akie Hirata;Shin Ishikane;F. Takahashi-Yanaga;M. Arioka;T. Okui;Chinatsu Nojiri;T. Sasaguri;N. Nakashima
中科院分区：
文献类型：
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作者：
Akie Hirata;Shin Ishikane;F. Takahashi-Yanaga;M. Arioka;T. Okui;Chinatsu Nojiri;T. Sasaguri;N. Nakashima
在实验模型中，已有研究表明肾素-血管紧张素系统抑制剂可预防肿瘤转移，但临床研究数据有限。我们的目的是通过分析多种原发性癌症的个体类型，探讨在癌症切除期间给予的肾素-血管紧张素系统抑制剂是否会影响随后的转移发展。本研究共纳入了2009年至2014年在九州大学医院接受原发性癌症切除术的4927例患者，并根据抗高血压药物的使用情况分为3组：肾素-血管紧张素系统抑制剂、其他药物和无药物。计算转移的累积发生率函数，将死亡视为竞争风险，并通过Gray检验检查组间差异。采用Fine和Gray模型评估多变量校正的偶然转移风险。在多变量校正分析中，皮肤癌和肾癌患者显示使用肾素-血管紧张素系统抑制剂的转移风险在统计学上更高（风险比[95%置信区间]分别为5.81 [1.07-31.57]和4.24 [1.71-10.53]）。对于胰腺癌，接受除肾素-血管紧张素系统抑制剂以外的降压药物治疗的患者转移风险显著增加（风险比[95%置信区间]，3.31 [1.43-7.69]）。未来需要更大规模的研究来确定肾素-血管紧张素系统抑制剂是否会增加皮肤癌和肾癌转移的风险，重点是特定的组织类型和与肾素-血管紧张素系统抑制剂使用相关的潜在因素。
Renin-angiotensin system inhibitors have been shown to prevent cancer metastasis in experimental models, but there are limited data in clinical studies. We aimed to explore whether renin-angiotensin system inhibitors administered during the period of cancer resection can influence the subsequent development of metastasis by analyzing multiple individual types of primary cancers. A total of 4927 patients who had undergone resection of primary cancers at Kyushu University Hospital from 2009 to 2014 were enrolled and categorized into 3 groups based on the use of antihypertensive drugs: renin-angiotensin system inhibitors, other drugs, and none. Cumulative incidence functions of metastasis, treating death as a competing risk, were calculated, and the difference was examined among groups by Gray’s test. Fine and Gray’s model was employed to evaluate multivariate-adjusted hazards of incidental metastasis. In the multivariate-adjusted analysis, patients with skin and renal cancers showed statistically higher risks of metastasis with the use of renin-angiotensin system inhibitors (hazard ratio [95% confidence interval], 5.81 [1.07–31.57] and 4.24 [1.71–10.53], respectively). Regarding pancreatic cancer, patients treated with antihypertensive drugs other than renin-angiotensin system inhibitors had a significantly increased risk of metastasis (hazard ratio [95% confidence interval], 3.31 [1.43–7.69]). Future larger studies are needed to ascertain whether renin-angiotensin system inhibitors can increase the risk of metastasis in skin and renal cancers, focusing on specific tissue types and potential factors associated with renin-angiotensin system inhibitor use.