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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

Hypertension Research volume 45, pages 1869–1881 (2022)Cite this article

Abstract

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.

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Acknowledgements

We are grateful to M. Nogami and C. Yato for their helpful support in data collection. The authors would like to thank Enago (www.enago.jp) for the English language review.

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Authors and Affiliations

  1. Medical Information Center, Kyushu University Hospital, Fukuoka, Japan

    Akie Hirata, Tasuku Okui, Chinatsu Nojiri & Naoki Nakashima

  2. Department of Pharmacology, School of Medicine, University of Occupational and Environmental Health, Japan, Fukuoka, Japan

    Shin Ishikane & Fumi Takahashi-Yanaga

  3. Department of Clinical Pharmacology, Faculty of Medical Sciences, Kyushu University, Fukuoka, Japan

    Masaki Arioka & Toshiyuki Sasaguri

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Hirata, A., Ishikane, S., Takahashi-Yanaga, F. et al. 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. Hypertens Res 45, 1869–1881 (2022). https://doi.org/10.1038/s41440-022-01038-4

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