Headline or hypothesis? ACE inhibitors/ARBs and decreased colon cancer risk

EBM Focus - Volume 15, Issue 27

Reference: Hypertension. 2020 Jul 6

You may have seen recent headlines suggesting that ACE inhibitors and ARBs reduce the risk of colon cancer based on a study from Hong Kong. But is that a conclusion we can really make with the available evidence? This recent population-based retrospective cohort study included patients aged ≥ 40 years who had colonoscopies between 2005 and 2013. Patients with prior colon cancer, colon resection, or inflammatory bowel disease were excluded, and the primary outcome of postcolonoscopy colorectal cancer was defined as colon cancer discovered between six months and three years after the index colonoscopy.

After exclusions, the authors looked at records and prescriptions for 187,897 patients (median age at index colonoscopy 60.6 years) and found that 854 (0.45%) were diagnosed with postcolonoscopy colorectal cancer. A total of 30,856 patients had used ACE inhibitors or ARBs within five years before the index colonoscopy (median use duration 3.3 years). Not surprisingly, patients on ACE inhibitors/ARBs were older and had a higher rate of diabetes and several other indicators of poor health. The authors used propensity score-matched analysis based on 21 items. After adjusting for propensity score, the rate of postcolonoscopy colorectal cancer was significantly lower for patients taking ACE inhibitors/ARBs for greater than two years (hazard ratio 0.77, 95% CI 0.6-0.97). Longer ACE inhibitors/ARB therapy duration within that time frame was also associated with a decreased postcolonoscopy colorectal cancer rate.

Propensity scores are theoretically a useful way to decrease the inherent bias of an observational study, but there has been concern about their overuse or misapplication. There are always unknown confounders not accounted for in the analysis, and thus propensity score analysis can give an exaggerated sense of confidence in data. Without randomization, the two groups can never be prognostically equal, leaving room for bias and an incorrect inference of a causal relationship. For example, a different recent retrospective analysis suggested that almost 80% of postcolonoscopy colorectal cancer is due to technical or administrative problems with the index colonoscopy rather than quickly growing cancers as previously suggested. If the experience were similar in this population, this could be a major source of bias not accounted for by the propensity analysis in this study. The utility of propensity analysis is dependent on which potential confounders the analysts deem important. At most, this study is hypothesis-generating for additional research, but for now we remain skeptical of drawing any conclusions about ACE inhibitors/ARBs and the risk of colorectal cancer.

For more information, see the topic Colorectal Cancer in DynaMed.

DynaMed EBM Focus Editorial Team

This EBM Focus was written by Dan Randall, MD, Deputy Editor for Internal Medicine at DynaMed. Edited by Alan Ehrlich, MD, Executive Editor at DynaMed and Associate Professor in Family Medicine at the University of Massachusetts Medical School, and Katharine DeGeorge, MD, MS, Associate Professor of Family Medicine at the University of Virginia and Clinical Editor at DynaMed.