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Response to: Do angiotensin-converting enzyme inhibitors not reduce the risk of pneumonia?

Hypertension Research (2025)Cite this article

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We are grateful to Dr. Tsukamoto for his comment [1], which offers an important perspective on our study. His paper highlighted key limitations of analyses using real-world healthcare databases and discussed potential selection biases inherent in retrospective cohort study designs. He also provided additional insight into alternative mechanisms by which renin-angiotensin-aldosterone system (RAAS) inhibitors may help prevent pneumonia—a topic that attracted much attention during the COVID-19 pandemic.

As outlined in his comment, several important confounders (e.g., cough sensitivity) were not available in the Longevity Improvement and Fair Evidence (LIFE) Study database. To address this limitation, we had conducted a sensitivity analysis to assess how strong the effects of unmeasured confounding are and how unbalanced the intergroup distribution of such confounders would have to be in order to explain a protective effect of angiotensin-converting enzyme inhibitors (ACEIs) against pneumonia. The sensitivity analysis indicated that it would be unlikely for any unmeasured confounder to be sufficiently strong and unequally distributed to account for this effect. As real-world healthcare databases frequently lack essential patient-level information, it is crucial to carefully evaluate potential confounders through detailed quantitative sensitivity and subgroup analyses.

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References

  1. Tsukamoto S. Do angiotensin-converting enzyme inhibitors not reduce the risk of pneumonia? Hypertens Res. 2024;47:2961–3.

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  1. Department of Health Care Administration and Management, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

    Ryosuke Uemura & Haruhisa Fukuda

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  1. Ryosuke Uemura
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  2. Haruhisa Fukuda
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Correspondence to Haruhisa Fukuda.

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Uemura, R., Fukuda, H. Response to: Do angiotensin-converting enzyme inhibitors not reduce the risk of pneumonia?. Hypertens Res (2025). https://doi.org/10.1038/s41440-025-02292-y

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