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Angiotensin receptor neprilysin inhibitor for the treatment of hypertension: a systematic review and meta-analysis

Hypertension Research volume 49, pages 469–485 (2026)Cite this article

Abstract

There is substantial evidence demonstrating that angiotensin receptor neprilysin inhibitors (Sacubitril/Valsartan – Sac/Val) significantly reduce sitting blood pressure (BP). However, comprehensive pooled analyses evaluating their effects on out-of-office BP in patients with systemic hypertension remain limited. We conducted a systematic literature search of PubMed, Cochrane Library, Scopus, Embase, and ClinicalTrials.gov for randomized and non-randomized studies comparing Sac/Val with other antihypertensive agents in the treatment of systemic hypertension, from inception to the end of May 2024. Outcomes included nighttime, daytime and 24-h mean ambulatory (ma) systolic/diastolic BP (maSBP/maDBP), ambulatory pulse pressure (PP), and office BP. Safety outcomes were also assessed. Fifteen randomized controlled trials (RCTs) and 4 observational studies representing 7548 patients were included. In RCTs, Sac/Val therapy was associated with greater reductions in out-of-office blood pressure compared to angiotensin receptor blockers (ARBs) and calcium channel blockers (CCBs). This included nighttime maSBP (mean difference [MD] −3.61 mmHg; 95% confidence intervals [CI] −4.86 to −2.36; p < 0.001) and maDBP (−2.11 mmHg; [−2.69 to −1.53]; p < 0.001); as well as daytime maSBP (−3.39 mmHg; [−4.58 to −2.21]; p < 0.001) and maDBP (−1.82 mmHg; [−2.82 to −0.82]; p < 0.001). Similarly, significant reductions in 24-h maSBP/maDBP, ambulatory PP, and office BP were observed with Sac/Val. Observational studies also demonstrated that Sac/Val significantly reduced office BP compared with ARBs and thiazide diuretics (p < 0.05). There were no significant differences in the incidence of adverse events between groups. In conclusion, Sac/Val effectively reduces both out-of-office and office BP and is well tolerated throughout the follow-up period.

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Acknowledgements

The authors would like to state gratitude to the graduate scholarship program for ASEAN or non-ASEAN countries, Chulalongkorn University.

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Authors and Affiliations

  1. Department of Pharmacy Practice, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand

    Hsu Myat Noe, Alisara Sangviroon Sujarit & Yotsaya Kunlamas

  2. Department of Social and Administrative Pharmacy, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand

    Bunchai Chongmelaxme

  3. Revolution Health Research Consulting (RHRC) group, Bangkok, Thailand

    Bunchai Chongmelaxme

  4. Division of Cardiovascular Medicine, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand

    Sarinya Puwanant

  5. Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China

    Franco Wing Tak Cheng

  6. Department of Pharmacology and Pharmaceutical Care, Faculty of Pharmaceutical Sciences, Huachiew Chalermprakiet University, Samut Prakan, Thailand

    Watsit Chaipatiwat

  7. Division of Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Burapha University, Chonburi, Thailand

    Anchana Pongpun

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Contributions

Conceptualization: HMN, YK, ASS, BC, SP; data curation: HMN, YK, ASS, BC, WC, AP; data analysis/interpretation: HMN, YK, ASS, BC, FWTC; statistical analysis: HMN, YK, ASS, BC; original manuscript drafting: HMN, YK, ASS, BC; manuscript review and editing: all authors; supervision and mentorship: YK, ASS, BC, FWTC, SP.

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Correspondence to Yotsaya Kunlamas.

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Noe, H.M., Sujarit, A.S., Chongmelaxme, B. et al. Angiotensin receptor neprilysin inhibitor for the treatment of hypertension: a systematic review and meta-analysis. Hypertens Res 49, 469–485 (2026). https://doi.org/10.1038/s41440-025-02406-6

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