Association between Proton Pump Inhibitor use and risk of Cardiovascular Disease
The American Journal of Gastroenterology:
Proton pump inhibitors (PPIs) are a class of effective medications used to treat various acid-related disorders. Their use in the clinical setting has increased rapidly and tremendously. PPIs are among the most commonly used medications worldwide.
However, the widespread availability of these agents has also contributed to inappropriate prescriptions and medication overuse.
Currently, the administration of PPIs is increasing in daily clinical practice, and there is growing concern regarding the potential long-term risks associated with these agents.
TAKE-HOME MESSAGE
Authors investigated cardiovascular risk due to proton pump inhibitor (PPI) treatment using a self-controlled case series (SCCS) study design.
This study minimized between-person confounding to assess the cardiovascular risk associated with the use of proton pump inhibitors (PPIs).
In a cohort of 303,404 Korean adults, although there appeared to be associations between PPI or H2 blocker exposures and the primary outcome (composite of stroke and MI) based on cohort designs, there was no association between PPI exposure and the primary outcome with the SCCS design.
These findings suggest against a causal relationship between PPI exposure and cardiovascular events and against discontinuation of PPI therapy in patients with appropriate indications owing to concerns about PPI-related cardiovascular risks in clinical practice.
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OBJECTIVES
Authors investigated cardiovascular risk due to proton pump inhibitor (PPI) treatment using a self-controlled case series (SCCS) study design, a type of case-only design and an approach to overcome between-person confounding in which individuals act as their own control.
METHODS
Authors conducted an SCCS study using the National Health Insurance Service-Health Screening cohort in Korea (2002-2015). The cohort included 303,404 adult participants without prior cardiovascular events, who were followed up until December 2015. The primary outcome was a composite of stroke or myocardial infarction. The SCCS method estimated the age-adjusted incidence rate ratio (IRR) between periods with and without exposure to PPI among patients with primary outcomes. As sensitivity analysis, conventional multivariable Cox proportional regression analyses were performed, which treated the exposure to PPI and H2blocker during follow-up as time-dependent variables.
RESULTS
In the SCCS design, 10,952 (3.6%) patients with primary outcomes were included. There was no association between PPI exposure and primary outcome. In the time-dependent Cox regression analyses, both PPI and H2blocker were associated with an increased risk of the primary outcome.
CONCLUSIONS
Negative findings in the SCCS design suggest that association between increased cardiovascular risk and PPI, frequently reported in prior observational studies, is likely due to residual confounding related to conditions with PPI treatment, rather than a true relationship.
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