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Effects of renin–angiotensin system inhibitors in cancer patients: a systematic review and meta-analysis of randomized controlled trials

Hypertension Research (2025)Cite this article

Abstract

Cardiotoxicity is a growing concern in cancer patients receiving chemotherapy. Renin–angiotensin system (RAS) inhibitors, including angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs), are widely used for cardiovascular protection, but their role in cancer care remains uncertain. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the effects of RAS inhibitors on cardiotoxicity, dyspnea, and quality of life (QOL) in patients with malignancies. A comprehensive literature search was performed using PubMed, Embase, Web of Science, and the Cochrane Library, from which 15 eligible RCTs were identified. These trials compared RAS inhibitor users and non-users. Group differences were analyzed using mean differences (MDs) or odds ratios (ORs), with heterogeneity assessed by the I² statistic. Pooled results suggested a possible association between RAS inhibitor use and higher left ventricular ejection fraction (LVEF) compared to controls (MD 4.42%, 95% CI –0.02 to 8.85; I² = 96%). Subgroup analysis revealed significant benefit in patients receiving HER2-targeted therapy and those undergoing non-specific chemotherapy, while no advantage was seen in patients treated with anthracyclines and HER2 blockade. RAS inhibitors showed limited benefit in anthracycline regimens. No significant reduction in cardiotoxicity was observed (OR 0.66, 95% CI 0.19–2.30). Additionally, two trials evaluating ACE inhibitors with beta-blockers demonstrated additive effects in preventing LVEF decline in high-risk populations. One trial also reported improved dyspnea with ACE inhibitors in lung cancer. RAS inhibitors may help preserve cardiac function in cancer patients, but current evidence is inconclusive. Confirmation through large-scale RCTs is warranted.

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Acknowledgements

We would like to thank the Japanese Society of Hypertension (JSH) working group “Onco-Hypertension” for advice on preparing this manuscript.

Japanese Society of Hypertension (JSH) working group “Onco-Hypertension”

Akira Nishiyama7, Mikio Mukai9, Satoshi Morimoto10, Yoshikiyo Ono11, Hidehiro Kaneko12,13, Satoshi Kidoguchi14, Naoki Sugano14, Kunihiro Nishimura15, Yoichi Nozato16, Koichi Node8, Shintaro Minegishi1, Yuichiro Yano5,6.

Author information

Author notes

  1. These authors contributed equally: Satoshi Ishii, Yohei Hanajima

Authors and Affiliations

  1. Department of Cardiology, Yokohama City University School of Medicine, Yokohama, Japan

    Satoshi Ishii, Naohiro Komura, Shintaro Minegishi, Yoshinori Okazaki, Akira Horigome, Masanari Asai, Takumi Tokoro, Tomoaki Ishigami & Kiyoshi Hibi

  2. Cardiovascular Center, Yokohama City University Medical Center, Yokohama, Japan

    Yohei Hanajima, Kyoko Hattori & Kiyoshi Hibi

  3. Department of Cardiology, Saiseikai Yokohamashi Nanbu Hospital, Yokohama, Japan

    Takumi Tokoro

  4. Chemotherapy Center, Yokohama City University Hospital, Yokohama, Japan

    Nobuyuki Horita

  5. Department of General Medicine, Juntendo University Faculty of Medicine, Tokyo, Japan

    Yuichiro Yano

  6. Noncommunicable Disease (NCD) Epidemiology Research Center, Shiga University of Medical Science, Otsu, Japan

    Yuichiro Yano

  7. Department of Pharmacology, Faculty of Medicine, Kagawa University, Kagawa, Japan

    Akira Nishiyama

  8. Department of Cardiovascular Medicine, Saga University, Saga, Japan

    Koichi Node

  9. Osaka Center for Cancer and Cardiovascular Disease Prevention, Osaka, Japan

    Mikio Mukai

  10. Department of Medicine, Tokyo Women’s Medical University Adachi Medical Center, Tokyo, Japan

    Satoshi Morimoto

  11. Department of Diabetes, Metabolism and Endocrinology, Tohoku University Hospital, Sendai, Miyagi, Japan

    Yoshikiyo Ono

  12. The Department of Cardiovascular Medicine, The University of Tokyo, Tokyo, Japan

    Hidehiro Kaneko

  13. The Department of Advanced Cardiology, The University of Tokyo, Tokyo, Japan

    Hidehiro Kaneko

  14. Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan

    Satoshi Kidoguchi & Naoki Sugano

  15. Department of Preventive Medicine and Epidemiology National Cerebral and Cardiovascular Center, Suita, Japan

    Kunihiro Nishimura

  16. Department of Geriatric and General Medicine, The University of Osaka, Graduate School of Medicine, Osaka, Japan

    Yoichi Nozato

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Consortia

Japanese Society of Hypertension (JSH) working group “Onco-Hypertension”

  • Akira Nishiyama
  • , Mikio Mukai
  • , Satoshi Morimoto
  • , Yoshikiyo Ono
  • , Hidehiro Kaneko
  • , Satoshi Kidoguchi
  • , Naoki Sugano
  • , Kunihiro Nishimura
  • , Yoichi Nozato
  • , Koichi Node
  • , Shintaro Minegishi
  •  & Yuichiro Yano

Corresponding author

Correspondence to Shintaro Minegishi.

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Conflict of interest

Mikio Mukai has received speaking honoraria from Daiichi Sankyo and Ferring Pharmaceuticals.

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Ishii, S., Hanajima, Y., Komura, N. et al. Effects of renin–angiotensin system inhibitors in cancer patients: a systematic review and meta-analysis of randomized controlled trials. Hypertens Res (2025). https://doi.org/10.1038/s41440-025-02402-w

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  • DOI: https://doi.org/10.1038/s41440-025-02402-w

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