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Antihypertensive treatment effect of two dual therapies according to sodium sensitivity

Hypertension Research volume 49, pages 340–349 (2026)Cite this article

Abstract

We investigated the blood pressure (BP) lowering efficacy of two dual antihypertensive therapies, the amlodipine/benazepril and benazepril/hydrochlorothiazide combinations, according to sodium sensitivity risk (SSR) as assessed by ambulatory BP monitoring (ABPM). In a multi-center, randomized, actively-controlled, parallel-group trial, patients with a clinic systolic/diastolic BP of 140 to 179/90 to 109 mmHg while on benazepril 10 mg daily monotherapy, received 24-week antihypertensive treatment with amlodipine/benazepril 5/10 mg (n = 213) or benazepril/hydrochlorothiazide 10/12.5 mg (n = 212). SSR was assessed with two 24-h ABPM parameters, BP dipper status at night and 24-h mean heart rate. The amlodipine/benazepril combination, compared with benazepril/hydrochlorothiazide combination, showed greater BP lowering effect in 304 patients with low/intermediate SSR, but smaller BP lowering effect in 121 patients with high SSR, with significant (P ≤ 0.046) interaction for 24-h, daytime and morning systolic BP. Indeed, in comparison with the benazepril/hydrochlorothiazide group, 24-h and daytime systolic BP reductions in the amlodipine/benazepril group were 4.19 and 5.17 mmHg, respectively, greater in patients with low/intermediate SSR, while morning systolic BP reductions was 10.8 mmHg smaller in patients with high SSR. Similar trends were observed for the other systolic BP measurements and diastolic BP measurements, although statistical significance was not attained (P ≥ 0.069). Sensitivity analysis in 367 patients with sustained hypertension was confirmatory. In conclusion, the antihypertensive treatment effect of the amlodipine/benazepril and benazepril/hydrochlorothiazide combinations was dependent on SSR as assessed by ABPM, with the former combination being more efficacious in patients with low/intermediate SSR, but less efficacious in patients with high SSR.

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Data availability

Consent given by study participants did not include data sharing with third parties. Anonymized data can be made available to investigators for targeted research based on a motivated request to be addressed to the corresponding author via jiguangwang@rjh.com.cn.

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Acknowledgements

The authors gratefully acknowledge the voluntary participation of the patients and the contribution of the investigators from 20 hospitals and community health centers.

The ACEI/CCB Versus ACEI/DIU Combination Antihypertensive Therapy in Chinese Hypertensive Patients (ACvAD) investigators

Kai Zhao7, Yihong Luo8, Bing Deng9, Xin Chen10, Yinglong Qiu11, Mei-Ling Wang12, Zhihong Zhou13, Leijun Wang14, Jiahong Wang15, Ji-Guang Wang16, Yan Li16, Guibin He17, Hong Yu18, Ping Wang19, Yingmin Lu20, Yanping Zhang21, Yong Luo22, Jianhua Chen23, Min Liu24, Qing Peng25, and Jianqiang Xiao26

Funding

The study was partially funded by Di’ao Pharmaceuticals (Chengdu, Sichuan Province, China). The study investigators were also supported by the National Natural Science Foundation of China (grants 82370426, 82270469, 82070432, and 81970353), the Ministry of Science and Technology (2022YFC3601302 and 2024ZD0527304), Beijing, China, the Shanghai Municipal Health Commission (202340035 and 2024ZZ1028 and a Grant for Leading Academics 2022LJ022), and the Shanghai Talent Work Bureau (an Oriental Talent Program BJWS2024086).

Author information

Authors and Affiliations

  1. Department of Cardiovascular Medicine, Centre for Epidemiological Studies and Clinical Trials, The Shanghai Institute of Hypertension, State Key Laboratory of Medical Genomics, Shanghai Key Laboratory of Hypertension, Department of Hypertension, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China

    Qi-Fang Huang, Di Zhang, Yan Li & Ji-Guang Wang

  2. Department of Cardiology, Chongming Branch of Shanghai Tenth People’s Hospital, Shanghai, China

    Yihong Luo & Kun Hu

  3. Department of Cardiology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China

    Qiong Wu

  4. Department of Cardiology, Suzhou Hospital of Anhui Medical University (Suzhou Municipal Hospital of Anhui Province), Suzhou, Anhui Province, China

    Hailong Qiu & Fei Xu

  5. Hypertension Center, Puyang People’s Hospital, Puyang, Henan Province, China

    Mei-Ling Wang

  6. Department of Hypertension, Ruijin Hospital North, Shanghai Jiaotong University School of Medicine, Shanghai, China

    Xin Chen

  7. Yiwu Beiyuan Central Health Center, Yiwu, Zhejiang Province, China

    Kai Zhao

  8. Chongming Branch of Shanghai Tenth people’s Hospital, Shanghai, China

    Yihong Luo

  9. LongHua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China

    Bing Deng

  10. Ruijin Hospital North, Shanghai Jiaotong University School of Medicine, Shanghai, China

    Xin Chen

  11. Suzhou Hospital of Anhui Medical University (Suzhou Municipal Hospital of Anhui Province), Suzhou, Anhui Province, China

    Yinglong Qiu

  12. Puyang People’s Hospital, Puyang, Henan Province, China

    Mei-Ling Wang

  13. Shanghai Pudong New District Zhoupu Hospital, Shanghai, China

    Zhihong Zhou

  14. Sijing Hospital of Songjiang District, Shanghai, China

    Leijun Wang

  15. Yangpu Hospital, Tongji University, Shanghai, China

    Jiahong Wang

  16. Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China

    Ji-Guang Wang & Yan Li

  17. Luodian Hospital of Baoshan District, Shanghai, China

    Guibin He

  18. Shanghai Punan Hospital of Pudong New District, Shanghai, China

    Hong Yu

  19. Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, Henan Province, China

    Ping Wang

  20. Chongming branch of Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China

    Yingmin Lu

  21. Dachang Branch of Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China

    Yanping Zhang

  22. Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan Province, China

    Yong Luo

  23. Shanghai TCM-Integrated Hospital, Shanghai, China

    Jianhua Chen

  24. Henan Province People’s Hospital, Zhengzhou, Henan Province, China

    Min Liu

  25. The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan Province, China

    Qing Peng

  26. Changzhou Wujin People’s Hospital, Changzhou, Jiangsu Province, China

    Jianqiang Xiao

Authors
  1. Qi-Fang Huang
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  2. Di Zhang
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  6. Hailong Qiu
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  7. Fei Xu
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  8. Mei-Ling Wang
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  9. Xin Chen
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  10. Yan Li
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  11. Ji-Guang Wang
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Consortia

on behalf of The ACEI/CCB Versus ACEI/DIU Combination Antihypertensive Therapy in Chinese Hypertensive Patients (ACvAD) investigators

  • Kai Zhao
  • , Yihong Luo
  • , Bing Deng
  • , Xin Chen
  • , Yinglong Qiu
  • , Mei-Ling Wang
  • , Zhihong Zhou
  • , Leijun Wang
  • , Jiahong Wang
  • , Ji-Guang Wang
  • , Yan Li
  • , Guibin He
  • , Hong Yu
  • , Ping Wang
  • , Yingmin Lu
  • , Yanping Zhang
  • , Yong Luo
  • , Jianhua Chen
  • , Min Liu
  • , Qing Peng
  •  & Jianqiang Xiao

Corresponding author

Correspondence to Ji-Guang Wang.

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Conflict of interest

JGW reports having received lecture and consulting fees from Novartis, Omron, Servier, and Viatris. The other authors declare no conflict of interest.

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Huang, QF., Zhang, D., Luo, Y. et al. Antihypertensive treatment effect of two dual therapies according to sodium sensitivity. Hypertens Res 49, 340–349 (2026). https://doi.org/10.1038/s41440-025-02382-x

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