The proton pump inhibitor (PPI) pantoprazole was not associated with any adverse events after long-term use, according to the results of the randomized COMPASS trial published in Gastroenterology.
The double-blind trial included 17,598 participants randomly assigned to pantoprazole 40 mg daily or placebo. All participants had stable cardiovascular disease and peripheral artery disease. There was also random assignment to rivaroxaban 2.5 mg twice daily with aspirin 100 mg once daily, rivaroxaban 5 mg twice daily, or aspirin 100 mg alone.
The median follow-up was 3.01 years. There was no significant difference in the primary efficacy outcome of the rivaroxaban/aspirin potion of the trial for the composite outcome of myocardial infarction, stroke or cardiovascular health.
No difference in safety was found between pantoprazole and placebo outcomes except for enteric infections and C difficile infection. The rate of enteric infections was 1.4% for pantoprazole compared with 1.0% for placebo (OR=1.33; 95% CI, 1.01-1.75). C difficile infection occurred twice as commonly in patients assigned pantoprazole compared with the placebo group, but the difference was not statistically significant.
Researchers led by Paul Moayyedi, MB, ChB, PhD, of The Population Health Research Institute, McMaster University and Hamilton Health Sciences, Hamilton, Ontario, pointed out that these results are in contrast to systematic reviews of observational studies that show associations between PPIs and pneumonia, fracture, and cerebrovascular events.
“A well known maxim of epidemiology is that association is not causation and these data suggest that most of these associations relate to residual confounding or biases that are inherent in observational studies,” the researchers wrote. “A significant proportion of patients are prescribed PPI therapy inappropriately and in these cases, it is reasonable to advocate strategies to discontinue acid suppression. However, when there is a clinical need for PPI therapy these data suggest that the benefits are likely to outweigh any putative risks.”
The trial was sponsored by Bayer.
Moayyedi P, Eikelboom JW, Bosch J, et al. Safety of proton pump inhibitors based on a large, multi-year, randomized trial of patients receiving rivaroxaban or aspirin. Gastroenterology. 2019;doi:10.1053/j.gastro.2019.05.056.