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Effectiveness and Safety of Clopidogrel Co-administered With Statins and Proton Pump Inhibitors: A Korean National Health Insurance Database Study

Title
Effectiveness and Safety of Clopidogrel Co-administered With Statins and Proton Pump Inhibitors: A Korean National Health Insurance Database Study
Authors
Kim M.-S.Song H.J.Lee J.Yang B.R.Choi N.-K.Park B.-J.
Ewha Authors
최남경
Issue Date
2019
Journal Title
Clinical Pharmacology and Therapeutics
ISSN
0009-9236JCR Link
Citation
Clinical Pharmacology and Therapeutics vol. 106, no. 1, pp. 182 - 194
Publisher
Nature Publishing Group
Indexed
SCI; SCIE; SCOPUS WOS scopus
Document Type
Article
Abstract
Simultaneous competition for cytochrome P450 (CYP) 2C19 and CYP3A4 might diminish clopidogrel's antiplatelet effect by impacting its metabolic activation. This pharmacoepidemiologic study investigated whether proton pump inhibitors (PPIs) and CYP3A4-metabolized statins individually and jointly increase thrombotic events by attenuating clopidogrel's effectiveness. From Korean nationwide claims data (2007–2015), we selected 59,233 patients who initiated clopidogrel and statins after coronary stenting and compared thrombotic risks by PPI or CYP3A4-metabolized statin use or both. PPIs were associated with increased thrombotic risks (hazard ratio (HR) 1.27, 95% confidence interval (CI) 1.12–1.45), unlike CYP3A4-metabolized statins (HR 1.03, 95% CI 0.98–1.07). PPIs with high CYP2C19-inhibitory potential were more relevant than those with low potential (HR 1.28, 95% CI 1.02–1.61). Joint effects of PPIs and CYP3A4-metabolized statins were nonsignificant (relative excess risk due to interaction −0.14, 95% CI −0.34 to 0.07). Concurrent PPIs were associated with increased thrombotic risks in patients receiving clopidogrel and statins; CYP3A4-metabolized statins did not exacerbate PPI-associated risks. © 2019 The Authors Clinical Pharmacology & Therapeutics © 2019 American Society for Clinical Pharmacology and Therapeutics
DOI
10.1002/cpt.1361
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신산업융합대학 > 융합보건학과 > Journal papers
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