Over recent years there has been a debate over whether the pharmacokinetic drug interaction between clopidogrel and proton pump inhibitors (PPIs) reduces the antiplatelet effects of clopidogrel and leads to an increased risk of vascular events. However in this study, the association with increased risk of myocardial infarction was independent of clopidogrel use, and there was also no association with age-related risks, or use of H2 blockers.
The researchers acknowledge several limitations to their study, the most important being that observational data may be subject to multiple confounders and it is possible that PPI usage is merely a marker of a sicker patient population. For example, they were unable to control for factors such as obesity and insulin resistance, and it may be that in some individuals PPIs were prescribed for angina that was misidentified as acid reflux. They also could not account for over-the-counter PPI usage, or differences in drug dose. They highlight that these findings are hypothesis generating, and a prospective randomised study in the general population is required before changing clinical practice.
The lead researcher told Reuters that although the results are compelling, the study does not prove that PPIs cause myocardial infarctions. A commentator noted that the data are interesting and add to an ongoing debate, but based on current knowledge of PPIs, including this new study, there is not have enough information to change guidelines.