Identification of the Components of Proton Pump Inhibitors and Potassium-Competitive Acid Blocker That Lead to Cardiovascular Events in Working-Age Individuals: A 12-Month Retrospective Cohort Study Using a Large Claims Database.

This study aimed to identify the components of proton pump inhibitors (PPIs) or potassium-competitive acid blocker (PCAB) that lead to cardiovascular events in individuals of working age. We analyzed large claims data of individuals who were administered PPIs or PCAB. We enrolled working-age individuals administered PPI or PCAB without cardiovascular history with a 12-month screening and 12-month observation period and determined the proportion of cardiovascular events and the predictive factors of cardiovascular events in this population. Among the eligible individuals, 0.5% (456/91098) had cardiovascular events during the 12-month observation period. Predictive factors for cardiovascular events were age for +1 year (p < 0.0001), male sex (p < 0.0001), hypertension (p = 0.0056), and diabetes mellitus (p < 0.0001). The cardiovascular disease risk was higher in working-age individuals administered lansoprazole than in those administered other drugs (vs. rabeprazole; p = 0.0002, vs. omeprazole; p = 0.0046, vs. vonoprazan; p < 0.0001, and vs. esomeprazole; p < 0.0001). We identified the risk for cardiovascular events in individuals being treated with lansoprazole. Lansoprazole is known for its higher CYP2C19 inhibition activity compared with other PPIs or PCAB. A possible mechanism by which lansoprazole may lead to cardiovascular events is inhibiting the generation of epoxyeicosatrienoic acids from arachidonic acids, an intrinsic cardioprotective activator via CYP2C19 inhibition. Thus, we recommend avoiding administering lansoprazole to working-age individuals require PPIs or PCAB.

Data resource profile: JMDC claims database sourced from health insurance societies.

JMDC, Inc. (JMDC) has created a database, using data collected from health insurance societies in Japan, consisting of ledgers of insureds, claims (for hospitalization, outpatient treatment, drug preparation, and dental treatment), and health checkup results. The earliest data are from the claims in January 2005, except dental claims from December 2009 and health checkup results from April 2008. Currently (the end of June 2020), the number of insureds included is approximately 9.8 million. This database is unique for Japan and has the following characteristics: (a) the basic population can be ascertained; (b) standardization is carried out using a dictionary; and (c) anonymized individual IDs can be followed on the basis of a time-series over various periods, with the earliest starting date being January 2005. However, it has certain limitations, in that the disease status and test results cannot be ascertained, and there is insufficient access to data for elderly people.

Data resource profile: JMDC claims databases sourced from Medical Institutions.

JMDC, Inc. (JMDC) has created a database, using data collected from medical institutions in Japan, consisting of claims (for hospitalization and outpatient treatment), diagnosis procedure combination (DPC) assessment forms, and clinical laboratory test values. The oldest data in this database that can be accessed relate to treatment in April 2014. Currently (the end of October 2019), the number of medical institutions is 218, consisting of 131 DPC-eligible hospitals and 87 DPC-ineligible hospitals. Using this database, it is possible to carry out an analysis that makes up for certain limitations of JMDC's another database of data from health insurance societies (eg, the disease status and test results cannot be ascertained, and there is insufficient access to data for elderly people). In addition, it is noteworthy that this database includes not only data from DPC-eligible hospitals but also data from some DPC-ineligible hospitals.