Effectiveness and Safety of Clopidogrel Co-administered With Statins and Proton Pump Inhibitors: A Korean National Health Insurance Database Study
- 주제(기타) Pharmacology & Pharmacy
- 설명문(일반) [Kim, Mi-Sook; Park, Byung-Joo] Seoul Natl Univ, Dept Prevent Med, Coll Med, Seoul, South Korea; [Kim, Mi-Sook; Yang, Bo Rain] Seoul Natl Univ Hosp, Med Res Collaborating Ctr, Seoul, South Korea; [Song, Hong Ji] Hallym Univ, Sacred Heart Hosp, Coll Med, Dept Family Med,Hlth Promot Ctr, Anyang, South Korea; [Lee, Joongyub] Inha Univ Hosp, Dept Prevent & Management, Incheon, South Korea; [Choi, Nam-Kyong] Ewha Womans Univ, Coll Sci & Ind Convergence, Dept Hlth Convergence, Seoul, South Korea
- 등재 SCIE, SCOPUS
- 발행기관 WILEY
- 발행년도 2019
- URI http://www.dcollection.net/handler/ewha/000000160490
- 본문언어 영어
- Published As http://dx.doi.org/10.1002/cpt.1361
- PubMed https://pubmed.ncbi.nlm.nih.gov/30648733
초록/요약
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.
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