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Comparison of the effects of angiotensin receptor–neprilysin inhibitors and thiazide diuretic/renin–angiotensin system inhibitor combination therapy in hypertensive patients: a retrospective cohort study

Journal of Human Hypertension volume 37, pages 1049–1055 (2023)Cite this article

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Abstract

Angiotensin receptor–neprilysin inhibitors (ARNIs) have been approved as antihypertensive agents in Japan, and thiazide diuretics (TZDs) are widely used concomitantly with renin–angiotensin system inhibitors (RASIs) for hypertension. This retrospective study included patients with hypertension who switched from RASI to ARNI therapy (ARNI group) and those who were prescribed TZDs with RASIs (TZD/RASI group). Drug-related changes in the estimated glomerular filtration rate (eGFR), blood pressure (BP), body weight (BW), serum electrolytes, uric acid (UA), and triglyceride levels were compared between the two groups. Overall, 70 participants (31 and 39 in the ARNI and TZD/RASI groups, respectively) were enrolled and observed for a median of 2 months. According to linear mixed models, compared with the TZD/RASI group, the ARNI group exhibited a significant change in mean eGFR of 3.71 mL/min/1.73 m2 [95% confidence interval (CI), 0.57–6.84; P = 0.02] from the time of switching drug to the next outpatient visit. Further, compared with the TZD/RASI group, the ARNI group exhibited significant changes in mean serum UA (−1.27; 95% CI, −1.66 to −0.88), sodium (1.22; 95% CI, 0.12 to −2.32), chloride (2.14; 95% CI, 0.75–3.52), and triglyceride (−52.1; 95% CI, −100.9 to −3.29) levels. Conversely, serum potassium levels, BW, and systolic and diastolic BP did not differ significantly between the two groups (P = 0.69, 0.44, 0.49, and 0.66, respectively). Compared with the combination therapy of TZD and RASI, ARNI therapy causes less renal dysfunction, hyperuricemia, and hypertriglyceridemia with fewer electrolyte abnormalities and no significant difference in antihypertensive effects.

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Fig. 1: Flowchart of the participant selection process.
Fig. 2: Changes in estimated glomerular filtration rate (eGFR) from baseline to follow-up between the study groups according to linear mixed models.

Data availability

The data from this study are available from the corresponding author upon reasonable request.

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Acknowledgements

The authors would like to thank all participants for their dedication to this research project.

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Authors and Affiliations

  1. Department of Endocrinology, Metabolism and Nephrology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan

    Ryunosuke Mitsuno, Kiyotaka Uchiyama, Takashin Nakayama, Rina Takahashi, Norifumi Yoshimoto, Shintaro Yamaguchi, Takeshi Kanda, Kaori Hayashi & Hiroshi Itoh

  2. Department of Nephrology, International University of Health and Welfare Narita Hospital, 852 Hatakeda, Narita, Chiba, 286-8520, Japan

    Kiyotaka Uchiyama & Naoki Washida

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  1. Ryunosuke Mitsuno
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Contributions

KU designed the study. RM and KU wrote the initial draft of the manuscript. RM, TN, NY, and SY contributed to data collection. RM, UK, TN, RT, NY, and SY contributed to the analysis and interpretation of data. NW, TK, KH, and HI supervised the manuscript. All authors have approved the final version of the manuscript and agree to be accountable for all aspects of the work as well as ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

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Correspondence to Kiyotaka Uchiyama.

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The authors declare no competing interests.

Ethical approval

This study was reviewed and approved by the Research Ethics Committee of Keio University, School of Medicine (approval number: 20221156) and performed in accordance with the principles of the Declaration of Helsinki.

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Mitsuno, R., Uchiyama, K., Nakayama, T. et al. Comparison of the effects of angiotensin receptor–neprilysin inhibitors and thiazide diuretic/renin–angiotensin system inhibitor combination therapy in hypertensive patients: a retrospective cohort study. J Hum Hypertens 37, 1049–1055 (2023). https://doi.org/10.1038/s41371-023-00851-9

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