PPI therapy not a risk factor for myocardial infarction, stroke

There appears to be no evidence that proton pump inhibitors (PPIs) confer heightened risk of myocardial infarction (MI) or ischaemic stroke (IS) in the first decade after treatment initiation, according to a study.

Researchers used administrative claims data and emulated a target trial that examined the risks of MI and IS in relation to treatment initiation with PPIs vs H₂-receptor antagonists (H₂RAs). They applied Cox models and weighted Kaplan-Meier estimators in the analysis.

The population comprised 1,143,948 PPI initiators and 36,229 initiators of H₂RA therapy. PPI initiators were older, more likely to suffer from reflux disease or Helicobacter pylori infection, and tended to take nonsteroidal anti-inflammatory drugs or anticoagulants.

There were 4,460 MI cases and 17,798 IS cases recorded over a mean follow-up of 6.2 years among PPI initiators. Meanwhile, a total of 156 MI and 595 IS events occurred over a mean follow up of 5.3 years among H₂RA initiators.

Multivariable analysis showed no association between PPI therapy and the incidence of MI or IS as compared with H₂RA. The hazard ratios (HRs) associated with 10 years of use of PPI vs H₂RA were 0.96 (95 percent confidence interval [CI], 0.80–1.16) for MI and 0.98 (95 percent CI, 0.89–1.08) for IS.

Survival curves evaluating the outcome-free survival among PPI therapy vs H₂RA therapy initiators were consistent with the findings. The same was true when comparing PPI initiation vs noninitiation, with HRs of 1.02 (95 percent CI, 0.94–1.10) for MI and 0.98 (95 percent CI, 0.94–1.02) for IS.

The present data should ease the concerns of physicians and patients regarding the potential cardiovascular consequences of starting an indicated PPI therapy. More studies are needed to examine the effects of long-term and high-dose PPIs.