PPIs Tied to Slightly Higher Colorectal Cancer Risk Than H2RAs With Long-Term Use

By Lisa Rapaport

July 15, 2021

(Reuters Health) - Although use of proton pump inhibitors (PPIs) overall may not be associated with an increased risk of colorectal cancer compared with histamine-2 receptor antagonists (H2RAs), a new study suggests there may be an increased risk with long-term PPI use.

During follow-up for a median of 4.9 years after treatment initiation, researchers saw 6,759 incident colorectal cancer cases among 1,293,49 PPI users and 1,264 cases among 292,387 H2RA users, for crude incidence rates of 105.5 versus 87.7 events per 100,000 person-years.

Overall, there was no significant difference in the risk of colorectal cancer with PPIs compared with H2RAs (hazard ratio 1.02).

The colorectal cancer risk associated with PPIs did appear to rise over time, however. Hazard ratios climbed from 0.93 with less than two years of PPI use, to 1.45 with 2 to 4 years of use, and to 1.60 with more than 4 years of use.

"PPIs are very effective medications when used as indicated," said lead study author Devin Abrahami, a researcher in Epidemiology, Biostatistics, and Occupational Health at McGill University in Montreal, Canada.

"However, most indications do not support long-term use, which is where an increased risk of colorectal cancer may be observed," Abrahami said by email.

After five years of use, researchers estimated that there would be one case of colorectal cancer for every 5,343 patients on PPIs, while at 10 years the incidence would climb to one colorectal cancer event for every 792 PPI users, researchers report in Gut.

One limitation of the study is that researchers only had data on prescriptions from general practitioners, excluding prescriptions from specialists or over-the-counter use of PPIs from the analysis. Researchers were also unable to assess the association between PPIs and specific stages of colorectal cancer or between PPIs and cancer at specific sites.

Another potential limitation is the lack of granular detail on the duration or dosing of short-term PPI usage, said Dr. Ziyad Al-Aly, chief of the Research and Development Service at the VA Saint Louis Health Care System.

"Although they do not say this clearly, it is likely that the majority of people in the less than 2 years exposure group were exposed/treated with PPIs for a very short period of time -- it could be days to weeks," Dr. Al-Aly, who wasn't involved in the study, said by email.

"This may explain the lack of association with cancer in this group," Dr. Al-Aly said, referring to the people in the study who used PPIs for less than 2 years.

It's also possible that the association between long-term PPI use and colorectal cancer might be explained at least in part by patients' underlying medical condition, said Ruben Abagyan, a professor at the Skaggs School of Pharmacy & Pharmaceutical Sciences at the University of California, San Diego, who wasn't involved in the study.

"The long term PPI use is more likely to be associated with more severe GI acid-imbalance issues, which, in turn, may lead to cancer," Abagyan said by email. Clinicians may also prescribe H2RAs more often for milder manifestations of GI issues, reserving PPIs for more severe cases.

"Thus, to some extent PPIs and H2RA may have a different association with the colorectal cancer outcome simply due to existing prescription practices," Abagyan said.

"The take-home message for clinicians is to follow prescriber recommendations for PPIs and do not exceed the recommended treatment duration," Abagyan advised. "I would not go as far as switching from PPIs to H2RAs."

SOURCE: https://bit.ly/3wCQyWB Gut, online July 1, 2021.