The long‐term risk for myocardial infarction or stroke after proton pump inhibitor therapy (2008‐2018)

Background: Proton pump inhibitors (PPIs) are well tolerated in the short term but have recently been associated with increased long-term cardiovascular risk in observational studies. Aims: To evaluate long-term risks of myocardial infarction (MI) and ischaemic stroke (IS) associated with PPI vs H2-receptor antagonist (H2RA) therapy in adults without pre-existing cardiovascular or cerebrovascular disease. Methods: Using administrative claims data (2008–2018), we emulated a target trial comparing MI and IS risks in new users of PPIs vs H2RAs. Treatment was identified using dispensed prescriptions. MI and IS were defined using hospital discharge codes. Inverse probability weighting was used to adjust for confounding, and Cox models to estimate hazard ratios (HRs). Survival curves were estimated using weighted Kaplan-Meier estimators. Results: We identified 1143948 new users of PPIs and 36229 new users of H2RAs who were free of prevalent cardiovascular or cerebrovascular disease. The mean follow-up time was 6.2years for PPI initiators and 5.3years for H2RA initiators. After 10years, the HRs for MI and IS were 0.96 (95% confidence interval (CI): 0.80-1.16) and 0.98 (95% CI: 0.89-1.08), respectively. Conclusions: This analysis of claims data of a large German health insurer did not provide evidence that PPI therapy increased the risk of MI or IS in the first decade after treatment initiation.