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. 2019 Nov;30(6):867-875.
doi: 10.1097/EDE.0000000000001065.

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

Phyo T Htoo  1 , Til Stürmer  1 , Michele Jonsson-Funk  1 , Virginia Pate  1 , Ross J Simpson Jr  2 , Jennifer L Lund  1
Affiliations

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

Phyo T Htoo et al. Epidemiology. 2019 Nov.

Abstract

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.

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Conflict of interest statement

Conflicts of interest:

P.T.H has no conflicts of interest. T.S. reports salary support from Center for Pharmacoepidemiology in the Department of Epidemiology, Gillings School of Global Public Health (current members: GlaxoSmithKline, UCB BioSciences, Merck), research support from AstraZeneca, Amgen, and ownership interest in Novartis, Roche, BASF, AstraZeneca, Johnson & Johnson, and Novo Nordisk.

R.J.S. is a paid consultant to Amgen, Pfizer and Merck.

Figures

Figure 1.
Figure 1.
Propensity score weighted cumulative incidence (from Kaplan–Meier estimator) of colorectal cancer among initiators of angiotensin converting enzyme inhibitors (ACEI) and/or angiotensin receptor blockers (ARB) versus beta blocker (BB), calcium channel blockers (CCB) and thiazide initiators according to intention-to-treat analyses
Figure 2.
Figure 2.
Propensity score weighted cumulative incidence (from Kaplan–Meier estimator) of colorectal cancer among initiators of angiotensin converting enzyme inhibitors (ACEI) and/or angiotensin receptor blockers (ARB) versus beta blocker (BB), calcium channel blockers (CCB) and thiazide initiators according to as treated analyses
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