To confirm tolerance of proton pump inhibitor (PPI) therapy with long-term treatment, an adequately powered, randomized trial was carried out, performing a 3 x 2 partial factorial, double-blind trial of 17,598 participants with stable cardiovascular disease and peripheral artery disease, randomly assigned to groups, given pantoprazole 40 mg daily (n = 8791), or placebo (n = 8807). Participants were also randomly assigned to groups that received rivaroxaban (2.5 mg twice daily with aspirin 100 mg once daily), rivaroxaban (5 mg twice daily), or aspirin (100 mg) alone.
Data was collected on development of pneumonia, C. difficile infection, other enteric infections, fractures, gastric atrophy, chronic kidney disease, diabetes, chronic obstructive lung disease, dementia, cardiovascular disease, cancer, hospitalizations, and all-cause mortality every 6 months. Patients were followed up for a median of 3.01 years, with 53,152 patient-years of follow up.
There was no statistical significant difference between the pantoprazole and placebo groups in safety events, except for enteric infections (1.4% vs. 1.0%) in the placebo group (OR 1.33). For all other safety outcomes, proportions were similar between groups, except for C. difficile infection, which was approximately twice as common in the pantoprazole vs. the placebo group, although there were only 13 events and the difference was not considered statistically significant.
It was concluded that in a large placebo-controlled, randomized trial, pantoprazole therapy is not associated with any adverse events when used for 3 years, with the possible exception of an increased risk of enteric infections.
Moayyedi, P., Eikelbloom, J., Bosch, J., et al for the COMPASS Investigators. “Safety of Proton Pump Inhibitors Based on a Large, Multi-Year, Randomized Trial of Patients Receiving Rivaroxaban or Aspirin.” Gastroenterology 2019; Vol. 157, pp. 682-691.