- As noted by the authors, this data mining exercise was useful to generate hypotheses about an association between PPI use and myocardial infarction (MI), but proof of a cause-and-effect relationship must come from studies that have more detail about individual patients.
- The absolute increased risk is modest. The authors note that for every 4,000 patients treated with PPIs only one would develop an MI.
- PPIs have clear and immediate benefits to decrease GERD symptoms and prevent bleeding. One must consider benefits as well as risk.
- There may be some other feature of GERD patients who take PPIs that explains the association. For example, patients with GERD who require more powerful medications might be more likely to be obese or smoke. Those factors might explain the observed MI risk. Other risk factors could also explain the mortality risk in the coronary angiogram cohort.
- If PPIs cause adverse cardiovascular outcomes, one might expect a dose response — longer use, consistent use or higher dose. The authors present no information on dose or duration. If PPIs cause heart attacks, one might also expect the increased risk with all drugs in this class, which was not observed for two of the five drugs studied.
- Further studies are warranted, however, especially as there is a potential mechanism by which PPIs could increase the risk of MI. The question can really only be answered with a randomized clinical trial.