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Regular proton pump inhibitor (PPI) use as prophylaxis for bleeds following percutaneous coronary intervention (PCI) was associated with a higher risk for gastric cancer, a retrospective study found.

In an analysis involving over 13,000 PCI patients, those prescribed PPI for prophylaxis had a greater risk for gastric cancer diagnosis (HR 3.55, 95% CI 1.46-8.66, P=0.005) and death (HR 4.18, 95% CI 1.09-16.08, P=0.037), reported Andrew Kei-Yan Ng, MD, of the Grantham Hospital in Hong Kong, and colleagues.

When the group looked at duration of use, only patients on PPIs for at least a year after PCI saw a significantly increased risk for gastric cancer (adjusted HR 2.06, 95% CI 1.01-4.18, P=0.046), according to the findings in .

"Previously, long-term PPIs were linked to gastric cancer, but the major criticism against direct causality was confounding by indication and reverse causality," Ng told MedPage Today.

In the study from Ng and his colleagues, patients were started on PPIs to prevent gastrointestinal (GI) bleeding from dual anti-platelet therapy (DAPT), he explained, which is guideline recommended to prevent stent thrombosis or cardiac events following PCI. Ng called the findings in a population without GI-specific symptoms alarming.

"While awaiting prospective data to better ascertain the causal relationship, physicians should judiciously assess the risks and benefits of chronic PPI use on prescription, and minimize the duration of exposure as far as possible," Ng and coauthors concluded.

For their study, the researchers evaluated 13,476 patients who underwent a first PCI from January 2004 to December 2017 at one of 14 hospitals in Hong Kong. Patients taking PPIs within 30 days before their procedure were excluded. Patients needed to survive a year post-PCI and have no known cancer for study inclusion. The primary outcome was a gastric cancer diagnosis at least a year after the procedure.

PPIs users (n=6,738) were defined as those taking the acid blockers after hospital admission or up to 30 days after PCI, then continuously for over 180 days. These patients took PPIs for a median of 1,314 days (IQR 718-1,901) and were matched 1:1 to non-users, defined as those with less than 2 weeks of PPI use within the year after their PCI.

In absolute numbers, seven non-PPI users (0.10%) and 17 users (0.25%) developed gastric cancer over a median follow-up of 7.1 years, translating to rates of 16.9 and 60.2 cases per 100,000 person-years, respectively. Death from gastric cancer occurred in three non-PPI users (0.04%) and eight users (0.12%), rates of 7.2 and 28.3 per 100,000 person-years. (Four patients developed gastric cancer within a year of the PCI procedure, all PPI users, and were thus excluded from the study, the authors noted.)

After adjusting for covariables and propensity score matching, PPI use was still significantly associated with gastric cancer (HR 1.98, 95% CI 1.07-3.66, P=0.030), according to Ng and colleagues.

Most than three-fourths of participants were men and nearly all were Chinese (94%). The average patient age was about 64 years and a little less than half were smokers. Patients had hypertension (57-59%), dyslipidemia (58-60%), and diabetes (29-32%). Between 64-74% of patients had an acute myocardial infarction, with over half requiring an emergency PCI. At discharge, most patients received P2Y12 inhibitors (prescribed for a year post-PCI), aspirin, statins, angiotensin blockers, and beta blockers.

Study limitations included its observational design, that cancer histology was unavailable to evaluate subtypes, and that nearly all of the patients were taking aspirin, which could restrict generalizability.

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