Abstract 1304: Cancer risk with initiation of angiotensin receptor blockers (ARBs) vs. angiotensin converting enzyme inhibitors (ACEIs).

Abstract Background: The comparative long-term effects of initiation of an angiotensin receptor blocker (ARB) and angiotensin-converting enzyme inhibitor (ACEI) on cancer risk remain uncertain. The objective of this study was to compare risks of cancer and non-cancer mortality between ARB and ACEI initiators among US veterans. Methods: This prospective cohort included 2,658,758 veterans with hypertension and no history of cancer who initiated either an ARB or an ACEI within the Veterans Health Administration between January 1, 2000, and December 31, 2017. Participants were followed from treatment initiation until the first occurrence of an outcome, death, loss to follow-up, or December 31, 2022 (the end of study). Initiation of ARB or ACEI treatment was determined from pharmacy dispensing records, excluding those with a history of cancer or who filled ARB or ACEI before the study period. The index date (baseline) was defined as the date of initiating either treatment. Inverse probability (IP) of treatment weighting was applied to adjust for 27 baseline covariates and estimate the intent-to-treat effect of ARB versus ACEI initiation. The co-primary outcomes were time to any cancer (ascertained from the VA Cancer Registry) and non-cancer mortality. Secondary outcomes included all-cause mortality, the composite of any cancer or death, incidence of specific cancers, and non-cancer-specific mortality. Cumulative incidence functions and risk ratios (RRs) with 95% confidence intervals (95% CI) were calculated using IP-weighted Aalen-Johansen estimator in the competing risks setting. Results: Among 2,658,758 veterans (median follow-up, 10 years; mean age, 63 years; 5% women; 76% non-Hispanic White; 15% Black), 90% initiated ACEIs and 10% initiated ARBs. ARB initiation was associated with a lower 10-year risk of any cancer (RR, 0.79; 95% CI, 0.75-0.83) and a similar 10-year risk of non-cancer mortality (RR, 1.03; 95% CI, 0.88-1.07) compared with ACEI initiation. Associations were consistent across most cancer types, except for inconclusive findings for breast and renal cancers. In subgroup analyses, a stronger inverse association between ARB initiation compared to ACEI initiation and cancer risk was observed among older patients (≥70 years). Conclusions and Relevance: ARB initiators had a lower risk of developing any cancer compared with initiation of ACEIs, with no observed difference in non-cancer or all-cause mortality. We also reported stronger inverse association for ARBs in older adults in subgroup analyses. Further research should clarify underlying biological mechanisms, confirm causality in randomized trials, and evaluate personalized antihypertensive strategies that incorporate cancer risk considerations. Citation Format: Caroline Himbert, Daniel K. Addo, Yizhe Xu, Tao He, Catherine G. Derington, Tom Greene, Jordana B. Cohen, Adam Bress, Sheetal Hardikar. Cancer risk with initiation of angiotensin receptor blockers (ARBs) vs. angiotensin converting enzyme inhibitors (ACEIs) abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 1304.