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Relationship between 2nd-generation angiotensin receptor blockers and the risk of hypotension in COVID-19 patients admitted to hospital

Hypertension Research (2024)Cite this article

Abstract

It has not yet been established whether angiotensin II receptor blockers (ARB), statins, and multiple drugs affect the severity of COVID-19. Therefore, we herein performed an observational study on the effects of 1st- and 2nd-generation ARB, statins, and multiple drugs, on COVID-19 in patients admitted to 15 Japanese medical facilities. The results obtained showed that ARB, statins, and multiple drugs were not associated with the primary outcome (odds ratio: 1.040, 95% confidence interval: 0.688–0.571; 0.696, 0.439–1.103; 1.056, 0.941–1.185, respectively), each component of the primary outcome (in-hospital death, ventilator support, extracorporeal membrane oxygenation support, and admission to the intensive care unit), or the secondary outcomes (oxygen administration, disturbed consciousness, and hypotension, defined as systolic blood pressure ≤90 mmHg). ARB were divided into 1st- and 2nd-generations based on their approval for use (before 2000 and after 2001), with the former consisting of losartan, candesartan, and valsartan, and the latter of telmisartan, olmesartan, irbesartan, and azilsartan. The difference of ARB generation was not associated with the primary outcome (odds ratio with 2nd-generation ARB relative to 1st-generation ARB: 1.257, 95% confidence interval: 0.613–2.574). The odd ratio for a hypotension as one of the secondary outcomes with 2nd-generation ARB was 1.754 (95% confidence interval: 1.745–1.763) relative to 1st-generation ARB. These results suggest that patients taking 2nd-generation ARB may be at a higher risk of hypotension than those taking 1st-generation ARB and also that careful observations are needed. Further studies are continuously needed to support decisions to adjust medications for co-morbidities.

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Acknowledgements

We thank Chie Nishiguchi, Ryoko Kotani for their excellent assistance. We thank all the participating facilities for their care towards patients with COVID-19 and cooperation during data entry.

Funding

The present study was funded by the Health and Labour Sciences Research Grant “Research for risk assessment and implementation of crisis management functions for emerging and re-emerging infectious diseases” provided by the Japanese Ministry of Health, Labour, and Welfare (Grant number 19HA1003) and by the Japan Agency for Medical Research and Development (Grant number 20ek0210106h0003).

Author information

Authors and Affiliations

  1. Division of Nephrology and Hypertension, National Cerebral and Cardiovascular Center, Osaka, Japan

    Fumiki Yoshihara, Tetsuya Arisato, Miki Matsuo & Masatsugu Kishida

  2. Division of Cardiology, Yokohama City University Medical Center, Yokohama city, Japan

    Yasushi Matsuzawa, Jin Kirigaya & Kazuo Kimura

  3. Department of Cardiovascular Medicine, Kumamoto University Hospital, Kumamoto, Japan

    Yasushi Matsuzawa

  4. Department of Preventive Medicine and Epidemiology, National Cerebral and Cardiovascular Center Research Institute, Suita, Osaka, Japan

    Kiyomasa Nakatsuka, Soshiro Ogata & Kunihiro Nishimura

  5. Advanced Critical Care and Emergency Center, Yokohama City University Medical Center, Yokohama City, Japan

    Ichiro Takeuchi

  6. Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, Yokohama, Japan

    Masaaki Konishi & Kouichi Tamura

  7. Department of Cardiology, Kanagawa Cardiovascular and Respiratory Center, Yokohama, Japan

    Kazuki Fukui

  8. Division of Cardiology, Fujisawa City Hospital, Fujisawa, Japan

    Kengo Tsukahara

  9. Department of Clinical Laboratory Medicine, Fujisawa City Hospital, Fujisawa, Japan

    Hiroyuki Shimizu

  10. Department of General Medicine, Kanagawa Prefectural Ashigarakami Hospital, Ashigara, Japan

    Keisuke Iwabuchi

  11. Division of Cardiology, Kanagawa Prefectural Ashigarakami Hospital, Ashigara, Japan

    Yu Yamada

  12. Division of Cardiology, Yokosuka City Hospital, Yokosuka, Japan

    Kenichiro Saka

  13. Department of Cardiology, Hyogo Prefectural Amagasaki General Medical Center, Amagasaki, Japan

    Yukihito Sato

  14. Department of Cardiology, Fukuoka University Hospital, Fukuoka, Japan

    Masahiro Ogawa

  15. Disease Control and Prevention Center, National Center for Global Health and Medicine, Tokyo, Japan

    Kayoko Hayakawa & Norio Ohmagari

  16. Department of Cardiology, National Hospital Organization Kyoto Medical Center, 1-1 Mukaihata-cho, Fukakusa, Fushimi-ku, Kyoto, Japan

    Syuhei Ikeda & Masaharu Akao

  17. Division of Cardiology, Fukuoka Tokushukai Hospital, Fukuoka, Japan

    Hideki Shimomura

  18. Kobe City Medical Center General Hospital, 2-1-1, Minamimachi, Minatojima, Chuoku, Kobe, Hyogo, Japan

    Yasuki Kihara

  19. Department of Nephrology, Kobe City Medical Center General Hospital, Kobe, Japan

    Akihiro Yoshimoto

  20. Critical Care Medical Center Sakai City Medical Center, Sakai, Japan

    Masanori Morita

  21. Department of Urology, Suita Municipal Hospital, Suita, Japan

    Norihiko Kumada

  22. Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Japan

    Satoshi Yasuda

  23. Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan

    Satoshi Yasuda

  24. Kumamoto University, Kumamoto, Japan

    Hisao Ogawa

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  1. Fumiki Yoshihara
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  2. Yasushi Matsuzawa
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  31. Satoshi Yasuda
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  32. Hisao Ogawa
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Corresponding author

Correspondence to Fumiki Yoshihara.

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Conflict of interest

FY reports research funding from AstraZeneca and Ono. KT reports honoraria from Novartis, AstraZeneca, Ono, Daiichi-Sankyo, Takeda, Otsuka, Bayer and Kyowa-Kirin, and research funding from AstraZeneca, Otsuka, Kaneka, and scholarship or donation from Bayer, Kyowa-Kirin, Otsuka, Takeda and Daiichi-Sankyo. SY reports honoraria from Daiichi Sankyo Co. Ltd. and Bayer Yakuhin, Ltd. and research funding from NEC Solution Innovators, Ltd., Daiichi Sankyo Co. Ltd. and Bayer Yakuhin, Ltd. and scholarship or donation from Abbott Medical Japan LLC, Amicus Therapeutics Co. Ltd., Otsuka Pharmaceutical Co. Ltd., Kowa Company Ltd., Sumitomo Dainippon Pharma Co. Ltd., Roche Diagnostics K.K. and endowed departments by commercial entities from Abbott Medical Japan LLC, Medtronic Japan Co. Ltd., Tesco Co. Ltd., Terumo Co., Nihon Kohden Co., Japan Lifeline Co. Ltd., Sound Wave Innovation CO. LTD., ONO PHARMACEUTICAL CO. LTD., SHIONOGI & CO. LTD., ZEON MEDICAL INC., Nippon Shinyaku Co. Ltd., Nippon Boehringer Ingelheim Co. Ltd., Otsuka Pharmaceutical Co. Ltd., Kowa Company, Ltd., Takeda Pharmaceutical Co. Ltd., Mochida Pharmaceutical Co. Ltd., BIOTRONIK JAPAN Co. Ltd., KANEKA MEDICAL PRODUCTS, FUKUDA DENSHI CO. LTD., and Philips Japan, Ltd. HO reports honoraria from Bayer Yakuhin. Other authors report no competing interests to disclose.

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The present study was approved by the National Cerebral and Cardiovascular Center Ethics Review (R20041). All procedures were performed in accordance with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.

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Yoshihara, F., Matsuzawa, Y., Nakatsuka, K. et al. Relationship between 2nd-generation angiotensin receptor blockers and the risk of hypotension in COVID-19 patients admitted to hospital. Hypertens Res (2024). https://doi.org/10.1038/s41440-024-01682-y

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