ACE (Angiotensin-Converting Enzyme) Inhibitors/Angiotensin Receptor Blockers Are Associated With Lower Colorectal Cancer Risk: A Territory-Wide Study With Propensity Score Analysis

Abstract

Whether ACE (angiotensin-converting enzyme) inhibitors and angiotensin receptor blockers modify colorectal cancer risk remains controversial. We aimed to determine association between their use and colorectal cancer risk after a negative baseline colonoscopy. This is a territory-wide retrospective cohort study recruiting patients aged ≥40 who had undergone colonoscopy between 2005 and 2013. Exclusion criteria included colorectal cancer detected <6 months of index colonoscopy, prior colorectal cancer, inflammatory bowel disease, and prior colectomy. The primary outcome was colorectal cancer diagnosed between 6 and 36 months after index colonoscopy. Sites of colorectal cancer were categorized as proximal (proximal to splenic flexure) and distal cancer. The adjusted hazard ratio of colorectal cancer with ACE inhibitor/angiotensin receptor blocker use (≥180-day use within 5 years before index colonoscopy) was derived by propensity score regression adjustment of 23 covariates (including patient’s factors, concurrent medication use, and endoscopy center’s performance). Of 187 897 eligible patients, 30 856 (16.4%) were ACE inhibitors/angiotensin receptor blocker users. Eight hundred fifty-four (0.45%) developed colorectal cancer between 6 and 36 months after index colonoscopy (proximal cancer: 147 [17.2%]). These drugs were associated with lower risk of colorectal cancer that developed <3 years after index colonoscopy (adjusted hazard ratio, 0.78 [95% CI, 0.64–0.96]), but not colorectal cancer that developed >3years (adjusted hazard ratio, 1.18 [95% CI, 0.88–1.57]); every single year increase in the drug use was associated with 5% reduction in adjusted hazard ratio risk. ACE inhibitors/angiotensin receptor blocker were associated with a lower colorectal cancer risk in a duration-response manner.