Renin–Angiotensin–Aldosterone System-based Antihypertensive Agents and the Risk of Colorectal Cancer Among Medicare Beneficiaries

BACKGROUND: Biologic evidence suggests that angiotensin II may play a role in tumor progression or growth. We compared the short-term colorectal cancer (CRC) risk among initiators of angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) versus guideline-recommended clinical alternatives (beta blockers, calcium channel blockers [CCB], and thiazides). METHODS: We conducted a new-user cohort study on U.S. Medicare beneficiaries aged over 65 years, who initiated antihypertensive monotherapy during 2007-2013 and were free of cancer diagnosis before drug initiation. Follow-up began 6 months postinitiation to allow time for the diagnostic delay. We estimated hazard ratios (HR) with 95% confidence intervals (CI) using propensity score weighted Cox regression, overall and stratified by time since drug initiation, and 5-year cumulative risk differences (RD) using Kaplan-Meier estimator. We assessed the potential for unmeasured confounding using supplemental data from Medicare Current Beneficiary Survey. RESULTS: For analyses without censoring for treatment changes, we observed 532 CRC events among 111,533 ACEI/ARB initiators. After a median follow-up of 2.2 years (interquartile range: 1.0-3.7), CRC risk was similar between ACEI/ARB and active comparators, with adjusted HRs of 1.0 (95% CI = 0.85, 1.1) for ACEI/ARB versus beta blockers, 1.2 (95% CI = 0.97, 1.4) for ACEI/ARB versus CCB and 1.0 (95% CI = 0.80, 1.3) for ACEI/ARB versus thiazide. Five-year RDs and as-treated analyses, which censored follow-up at medication changes, produced similar findings. CONCLUSIONS: Based on real-world antihypertensive utilization patterns in Medicare beneficiaries, our study suggests no association between ACEI/ARB initiation and the short-term CRC risk.