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July 26, 2026PLoS ONEOpen Access

Long-term ACE inhibitor use linked to ~15% lower overall cancer risk vs ARBs.

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Why the study?

Although the cardiovascular and renal benefits of ACEIs and ARBs are well established, uncertainty remains regarding their long-term associations with cancer risk.

Does exclusive treatment with ACEIs reduce the risk of cancer compared to ARBs in hypertensive adults?

Population

346,405 exclusive ACEI users and 77,018 exclusive ARB users aged 40 years or older

Comparison

Exclusive treatment with ACEIs vs exclusive treatment with ARBs

Design

Retrospective cohort study

Follow-up

From 2002 through 2024

Key result

Exclusive long-term treatment with ACE inhibitors was associated with lower overall odds of developing cancer compared to ARB therapy (OR 0.851), although associations varied across specific cancer types.

Authors

BBBelle Tamir BrahmsSAShani AfekMHMichael Hopp

Discussion

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Overview

Should not yet influence antihypertensive choice; leaves open differential cancer associations requiring prospective validation.

Key Points

  • To compare cancer incidence among patients treated exclusively with ACEIs versus ARBs.
  • Retrospective cohort study using electronic health records from Clalit Health Services.
  • Included hypertensive adults aged 40 and older, free of cancer on January 1, 2000.
  • Final cohort consisted of 346,405 ACEI users and 77,018 ARB users, with follow-up from 2002 to 2024.
  • ACEI therapy was associated with lower overall odds of cancer compared to ARB therapy.
  • Variations in cancer types observed; lower odds for several malignancies among ACEI users.
  • Differences in age at diagnosis and time to diagnosis noted between treatment groups.

Study Design

Type

Cohort (n=423,423)

Structured PICO

Does exclusive treatment with ACEIs reduce the risk of cancer compared to ARBs in hypertensive adults?

P
Population
423,423 hypertensive adults aged 40 years or older, free of cancer at baseline, treated exclusively with ACEIs or ARBs and followed for up to 23 years.
E
Exposure
Exclusive treatment with Angiotensin-converting enzyme inhibitors (ACEIs)
C
Comparator
Exclusive treatment with Angiotensin receptor blockers (ARBs)
O
Outcome
Diagnosis of any cancersafety

Main Result

Odds Ratio: 0.851 (95% CI 0.838–0.865)

Absolute Event Rate: 56.5% vs 61.6%

p-value: p=<0.001

In a large retrospective cohort, long-term exclusive use of ACE inhibitors was associated with a lower risk of cancer compared to ARBs, contributing to the safety profile evaluation of RAAS-modulating therapies.

Limitations

  • Observational retrospective cohort design cannot establish causality.
  • Residual confounding remains possible despite adjustment for demographic and exposure-related factors.
  • Treatment allocation was not random, and prescribing patterns may have differed according to unmeasured clinical characteristics.
  • Study population was derived from a single national healthcare organization and may not be fully representative of other healthcare systems.
  • Potential influence of unmeasured clinical and behavioral factors cannot be completely excluded.
  • Observational design precludes causal inference

Cite This Study

Brahms et al. (2026) conducted a cohort in Hypertension (n=423,423). Angiotensin-converting enzyme inhibitors (ACEIs) vs. Angiotensin receptor blockers (ARBs) was evaluated on Diagnosis of any cancer (OR 0.851, 95% CI 0.838-0.865, p=<0.001). Exclusive long-term treatment with ACE inhibitors was associated with lower overall odds of developing cancer compared to ARB therapy (OR 0.851), although associations varied across specific cancer types.

synapsesocial.com/papers/6a65a468d3aea3239cd770bahttps://doi.org/10.1371/journal.pone.0354248
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