Comprehensive Safety Evaluation of Proton Pump Inhibitors

Abstract

Objective: This study1) examined trends in proton pump inhibitor (PPI) use and associated healthcare spending among the U.S. population, 2) identified adverse outcomes associated with PPI use, and 3) conducted a systematic review and meta-analysis to examine the association between PPIs and myocardial infarction (MI) and gastric cancer (GC). Methods: The 2002-2017 Medical Expenditure Panel Survey was used to examine PPI use and spending trend and multivariable model was used to identify patient factors associated with PPI use. The 2004-2019 U.S FDA Adverse Event Reporting System (FAERS) data were analyzed and safety signals of MI, chronic kidney disease (CKD), and GC were evaluated using disproportionality analyses. A 5% random sample of the 2013-2016 Medicare administrative claims data was used to assess the associations of MI, CKD, and heart failure (HF) with PPI use employing a new user cohort design. Finally, clinical trials and observational studies were included to assess the associations between PPIs with MI and GC. Results: Trends in prescription PPI use increased significantly in 2002-2017, overall and in patient subgroups. Individuals who were aged >25, female, non-Hispanic Whites, residing in the Northeast, with low income, having public or private health insurance, obese or overweight, having poor health status, and having more comorbidities had higher likelihoods of using PPIs. The FAERS analyses identified disproportionate signals in CKD and GC AEs reporting. The reporting for CKD AEs might be impacted by publication bias. The Medicare claims data analyses found a decreased risk of MI for new users of PPI compared to H2 blocker, while associations in risk of CKD and HF with PPI use were observed. For individual PPIs, only pantoprazole users showed an increase in the risk of MI compared to omeprazole users. Finally, meta-analysis found no association between PPI use and risk of MI or GC among RCTs, but significant associations appeared after adding evidence from observational studies. Conclusion: Prescription PPI use increased significantly among U.S population. Findings of this study suggested no or limited risk of MI with PPI use. Further longitudinal studies are warranted to investigate the association between PPI use and GC.