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A comparative analysis of ACE Inhibitors and ARBs as cancer risk factors
Belle Tamir Brahms1, Shani Afek1,2, Michael Hopp3
1Department of Family Medicine, Clalit Health Services, Sharon-Shomron, Israel.
Importance:
Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are widely prescribed antihypertensive agents. Although their cardiovascular and renal benefits are well established, uncertainty remains regarding their long-term associations with cancer risk.
Objective:
To compare cancer incidence among patients treated exclusively with ACEIs or ARBs in a large population-based cohort with long-term follow-up.
Design, Setting, And Participants:
Retrospective cohort study using electronic health records from Clalit Health Services, Israel's largest healthcare organization. The source population included hypertensive adults aged 40 years or older who were free of cancer on January 1, 2000 (n = 1,048,575). After applying eligibility criteria and excluding patients who switched between treatment groups or were non-compliant with therapy, the final analytic cohort included 346,405 exclusive ACEI users and 77,018 exclusive ARB users.
Exposure:
Exclusive treatment with either ACEIs or ARBs. Cancer incidence analyses were conducted during an active follow-up period from 2002 through 2024, allowing for a two-year exposure window.
Main Outcomes And Measures:
The primary outcome was diagnosis of any cancer. Secondary outcomes included the ten most prevalent cancer types diagnosed during follow-up. Cancer incidence rates, odds ratios (ORs), age at diagnosis, and time from treatment initiation to cancer diagnosis were compared between treatment groups after adjustment for age, sex, and exposure duration.
Results:
During follow-up, overall cancer incidence differed between treatment groups. ACEI therapy was associated with lower overall odds of cancer than ARB therapy. Associations varied across specific cancer types, with lower odds observed among ACEI users for several common malignancies, whereas no meaningful difference was observed for leukemia. Differences in age at diagnosis and time to diagnosis were also observed between treatment groups.
Conclusions And Relevance:
In this large population-based cohort, long-term cancer risk differed between patients treated exclusively with ACEIs and those treated exclusively with ARBs. While the observational design precludes causal inference, the findings contribute to the ongoing evaluation of the long-term oncologic safety profiles of RAAS-modulating therapies. Further prospective and mechanistic studies are needed to clarify the biological basis and clinical significance of these associations.
Insights
Long-term use of angiotensin-converting enzyme inhibitors (ACEIs) was linked to lower cancer odds compared to angiotensin receptor blockers (ARBs). This study evaluated cancer incidence in patients exclusively using ACEIs or ARBs.
Area of Science:
- Cardiovascular Medicine
- Oncology
- Pharmacology
Background:
- Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are common treatments for hypertension.
- While their cardiovascular and renal benefits are known, their long-term impact on cancer risk is unclear.
Purpose of the Study:
- To compare cancer incidence between patients exclusively treated with ACEIs and those exclusively treated with ARBs.
- To investigate the long-term oncologic safety profiles of these RAAS-modulating therapies.
Main Methods:
- Retrospective cohort study using electronic health records from Clalit Health Services.
- Included hypertensive adults aged 40+ free of cancer, comparing exclusive ACEI users (346,405) and ARB users (77,018).
- Analyzed cancer incidence from 2002-2024, adjusting for age, sex, and exposure duration.
Main Results:
- Overall cancer incidence differed between the ACEI and ARB groups.
- ACEI therapy was associated with lower overall odds of cancer compared to ARB therapy.
- Specific cancer type associations varied, with lower odds for ACEI users in several common malignancies; no significant difference was found for leukemia.
Conclusions:
- Long-term cancer risk appears to differ between exclusive ACEI and ARB users.
- Findings suggest potential differences in oncologic safety profiles, though causal inference is limited.
- Further research is needed to understand the biological basis and clinical significance of these observed associations.
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