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Effectiveness and Safety of Clopidogrel Co‐administered With Statins and Proton Pump Inhibitors: A Korean National Health Insurance Database Study
Author(s) -
Kim MiSook,
Song Hong Ji,
Lee Joongyub,
Yang Bo Ram,
Choi NamKyong,
Park ByungJoo
Publication year - 2019
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1002/cpt.1361
Subject(s) - clopidogrel , cyp2c19 , medicine , pharmacology , hazard ratio , cyp3a4 , statin , atorvastatin , proton pump inhibitor , cyp3a5 , confidence interval , cytochrome p450 , aspirin , chemistry , metabolism , biochemistry , genotype , gene
Simultaneous competition for cytochrome P450 ( CYP ) 2C19 and CYP 3A4 might diminish clopidogrel's antiplatelet effect by impacting its metabolic activation. This pharmacoepidemiologic study investigated whether proton pump inhibitors ( PPI s) and CYP 3A4‐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 CYP 3A4‐metabolized statin use or both. PPI s were associated with increased thrombotic risks (hazard ratio ( HR ) 1.27, 95% confidence interval ( CI ) 1.12–1.45), unlike CYP 3A4‐metabolized statins ( HR 1.03, 95% CI 0.98–1.07). PPI s with high CYP 2C19‐inhibitory potential were more relevant than those with low potential ( HR 1.28, 95% CI 1.02–1.61). Joint effects of PPI s and CYP 3A4‐metabolized statins were nonsignificant (relative excess risk due to interaction −0.14, 95% CI −0.34 to 0.07). Concurrent PPI s were associated with increased thrombotic risks in patients receiving clopidogrel and statins; CYP 3A4‐metabolized statins did not exacerbate PPI ‐associated risks.