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Japan has health insurance provided by the social insurance system 1 (referred to below simply as "health insurance"), and when a citizen is examined and/or treated at a medical institution, he/ she presents to that institution a health insurance certificate containing information identifying him/herself and his/her insurance provider, and he/she is then responsible for only a fixed proportion of the medical expenses. The medical institution invoices the insurance provider for the remainder of the sum, via a claims processing and payment organization, on the basis of information in the health insurance certificate. Health insurance is provided by multiple bodies, on the basis of occupation, geography, and age (eg, elderly and geriatric), as follows: 2 • People aged 75 or older can join the medical care system for the late elderly, administered by local governments. • People less than 75 years old, primarily those who are employees of small, medium-sized, or long-established businesses, and/or are in temporary employment, and their dependents, are covered by health insurance administered by the Japan Health Insurance Association, except for employment-related injury. • People less than 75 years old, primarily those who are employees of large businesses, and their dependents, are covered by health insurance administered by health insurance societies, except for employment-related injury.

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.