PPI use not linked to cardiovascular disease risk

The association between proton pump inhibitor (PPI) use and increased cardiovascular disease risk, as seen in many observational studies, is probably caused by residual confounding related to conditions with PPI treatment instead of a true correlation, as suggested by negative findings in a self-controlled case series (SCCS) study.

A group of researchers performed an SCCS study using the National Health Insurance Service-Health Screening cohort in Korea (2002‒2015). A total of 303,404 adults without prior cardiovascular events, who were followed up until December 2015, were included in the cohort.

A composite of stroke or myocardial infarction served as the primary outcome of the study. The researchers used the SCCS method to estimate the age-adjusted incidence rate ratio between periods with and without exposure to PPI among patients with the primary outcome.

Conventional multivariable Cox proportional regression analyses were also conducted, treating the exposure to PPI and H2 blocker during follow-up as time-dependent variables.

Overall, 10,952 (3.6 percent) patients with primary outcomes were included in the SCCS design. No association was observed between PPI exposure and the primary outcome (incidence rate ratio, 0.98, 95 percent confidence interval [CI], 0.89‒1.09).

In the time-dependent Cox regression analyses, both PPI (adjusted hazard ratio [aHR], 1.36, 95 percent CI, 1.24‒1.49) and H2 blocker (aHR, 1.46, 95 percent CI, 1.38‒1.55) contributed to an increased risk of the primary outcome.