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  • Special Issue: Current evidence and perspectives for hypertension management in Asia
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Comparison between sacubitril/valsartan and thiazide diuretics among patients with uncontrolled hypertension in Japan

Hypertension Research volume 48, pages 2058–2071 (2025)Cite this article

Abstract

Although renin-angiotensin system (RAS) inhibitors and calcium channel blockers are widely used to treat hypertension in Japan, <10% of patients use thiazides. This study aimed to evaluate differences in the efficacy and safety of sacubitril/valsartan and thiazide diuretics. Patients with poor blood pressure (BP) control, despite combination treatment with RAS inhibitors and calcium channel blockers, were included in the study. Patients treated with thiazides (THZ group, n = 306) and those who switched from RAS inhibitors to sacubitril/valsartan (SacVal group, n = 433) were compared. Propensity score analysis with inverse probability weighting was performed. A significantly higher target BP achievement rate was observed in the SacVal group than in the THZ group (4 months, 37% vs. 26%, p < 0.001). In a general linear mixed model, significant decreases in office and home BP were observed in both groups (p < 0.001); however, no significant interaction effects were observed between the drug type and time course. Discontinuation of the treatment by adverse events was significantly more frequent in THZ group (10%) than in SacVal group (3%), with a hazard ratio [95% confidence interval] of 3.47 [1.78, 6.76] (p < 0.001). In the model using the propensity score, compared with THZ group, significantly lower levels of office and home systolic BP, uric acid, glycated hemoglobin A1c, and higher levels of eGFR were observed in SacVal group (p = 0.04, 0.002, <0.001, 0.01, and 0.02, respectively). In conclusion, comparable BP reduction and positive effects on metabolic parameters were observed with sacubitril/valsartan treatment, with better treatment tolerability than thiazide diuretics.

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Data availability

Data are available from the Review Board of Kanagawa Medical Association, Kanagawa Prefecture to investigators bound by confidential agreements. Contact details: Kazuo Kobayashi Kazuo Kobayashi, M.D., Ph.D, Committee of Hypertension and Kidney disease, Kanagawa Physicians Association, Yokohama, Kanagawa Prefecture, Japan, E-mail: k-taishi@xc4.so-net.ne.jp.

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Acknowledgements

We are grateful to all participants and acknowledge the support of the members of the Kanagawa Physicians Association, especially Noriyuki Asaba, Motohiko Okabe, Masashi Otsuka, and Kazuyoshi Sato, who contributed considerably to data collection.

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Authors and Affiliations

  1. Committee of Hypertension and Kidney disease, Kanagawa Physicians Association, Yokohama, Kanagawa Prefecture, Japan

    Kazuo Kobayashi, Keiichi Chin, Hideo Shimura, Shun Ito, Toshinao Tsuge, Hiroyuki Sakai, Takayuki Furuki, Atsushi Matsuzaki, Shinichi Nakajima, Nobukazu Takada, Hareaki Yamamoto, Hiroshi Takeda, Takamasa Iwasawa, Kouichi Tamura & Akira Kanamori

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

    Kazuo Kobayashi, Mari Sotozawa, Hiromichi Wakui & Kouichi Tamura

  3. Department of nephrology, Yokohama Sakae Kyosai Hospital, Yokohama, Japan

    Kyoji Chiba

  4. Department of Nephrology, Kitasato University School of Medicine, Sagamihara, Japan

    Togo Aoyama

  5. Division of Nephrology, Endocrinology and Metabolism, Department of Internal Medicine, Tokai University School of Medicine, Isehara, Japan

    Masao Toyoda

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  1. Kazuo Kobayashi
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Correspondence to Kazuo Kobayashi.

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Conflict of interest

HW has received research supports from AstraZeneca, Otsuka Pharmaceutical, and Kaneka Corporation, and honoraria from AstraZeneca, Otsuka Pharmaceutical, Kaneka Corporation, Kyowa Kirin, Sanwa Kagaku, Chugai Pharma, Kowa, Otsuka Pharmaceutical, Novartes, Mitsubishi-Tanabe Pharma, Bayer, and Daiichi-Sankyo Pharma. MT received lecture fees from Boehringer Ingelheim, Eli Lilly, Novo Nordisk, Sumitomo, and Mitsubishi Tanabe and received subsidies from Super Light Water, TAKAGI, Roche DC, and LifeScan. KT has received honoraria/lecture fee from AstraZeneca, Novartes, Bayer, Otsuka Pharmaceutical, Boehringer Ingelheim, Fuji Pharma, Kyowa Kirin, Ono Pharmaceutical, Sanwa Kagaku, Mochida Pharmaceutical, Kowa, Eli Lilly, Novo Nordisk, commissioned clinical trials, contract research and joint research funding: AstraZeneca, Bayer, Novartis, Chinook, Otsuka Medical Devices, Novo Nordisk, Terumo, Variatris, and Kowa, and, Scholarship donations: Otsuka Pharmaceutical, Bayer, Mochida Pharmaceutical, and Boehringer Ingelheim.

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Kobayashi, K., Sotozawa, M., Chin, K. et al. Comparison between sacubitril/valsartan and thiazide diuretics among patients with uncontrolled hypertension in Japan. Hypertens Res 48, 2058–2071 (2025). https://doi.org/10.1038/s41440-025-02236-6

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