Concerns regarding the long-term carcinogenic potential of renin–angiotensin system (RAS) inhibitors have generated considerable debate over the past decade. To better clarify this association, a comparative analysis published in PLOS ONE evaluated the relationship between angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) and the risk of developing cancer. Using a large real-world population dataset, the investigators compared cancer incidence among patients receiving ACEIs or ARBs while adjusting for relevant demographic and clinical confounding factors.
The study assessed the occurrence of overall cancer as well as several site-specific malignancies among patients treated with either drug class. After comprehensive statistical adjustment, the analysis demonstrated no significant difference in the overall risk of cancer between ACEI and ARB users. These findings suggest that neither class confers a clinically meaningful increase in overall cancer incidence, providing reassurance regarding the long-term safety of RAS inhibition in routine clinical practice.
Although overall cancer risk was comparable, the investigators observed modest differences in the incidence of certain individual cancer types. Some site-specific malignancies appeared more frequently in one treatment group than the other; however, these associations were generally small, inconsistent across analyses, and should be interpreted cautiously because of the observational nature of the study. Residual confounding, differences in baseline patient characteristics, treatment duration, lifestyle factors, and healthcare utilization may have influenced these findings.
The biological relationship between RAS inhibition and cancer remains complex. Experimental evidence suggests that angiotensin II signalling may influence tumour angiogenesis, inflammation, cellular proliferation, and apoptosis. Consequently, both ACEIs and ARBs have been hypothesized to exert either protective or adverse effects on carcinogenesis. However, clinical evidence from randomized trials, observational studies, and meta-analyses has remained inconsistent. The present analysis adds to the growing body of evidence indicating that any potential differences between ACEIs and ARBs are unlikely to translate into a meaningful change in overall cancer risk.
Overall, the study supports current clinical practice by reinforcing that treatment decisions between ACEIs and ARBs should continue to be guided primarily by cardiovascular and renal indications, patient comorbidities, tolerability, and guideline recommendations rather than concerns regarding cancer risk. Further prospective studies with longer follow-up and mechanistic investigations are warranted to better understand the observed site-specific associations and their potential biological significance.
Link: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0354248
