Effectiveness and Safety of Clopidogrel Co-administered With Statins and Proton Pump Inhibitors

A Korean National Health Insurance Database Study

Mi Sook Kim, Hong Ji Song, Joongyub Lee, Bo Ram Yang, Nam Kyong Choi, Byung Joo Park

Research output: Contribution to journalArticleResearchpeer-review

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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.

Original languageEnglish
Pages (from-to)182-194
Number of pages13
JournalClinical Pharmacology and Therapeutics
Volume106
Issue number1
DOIs
StatePublished - 1 Jul 2019

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clopidogrel
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Proton Pump Inhibitors
Cytochrome P-450 CYP3A
National Health Programs
Databases
Safety
Confidence Intervals
Cytochrome P-450 Enzyme System

Cite this

@article{7581593158464023a0c33586d928c312,
title = "Effectiveness and Safety of Clopidogrel Co-administered With Statins and Proton Pump Inhibitors: A Korean National Health Insurance Database Study",
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.",
author = "Kim, {Mi Sook} and Song, {Hong Ji} and Joongyub Lee and Yang, {Bo Ram} and Choi, {Nam Kyong} and Park, {Byung Joo}",
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Effectiveness and Safety of Clopidogrel Co-administered With Statins and Proton Pump Inhibitors : A Korean National Health Insurance Database Study. / Kim, Mi Sook; Song, Hong Ji; Lee, Joongyub; Yang, Bo Ram; Choi, Nam Kyong; Park, Byung Joo.

In: Clinical Pharmacology and Therapeutics, Vol. 106, No. 1, 01.07.2019, p. 182-194.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - Effectiveness and Safety of Clopidogrel Co-administered With Statins and Proton Pump Inhibitors

T2 - A Korean National Health Insurance Database Study

AU - Kim, Mi Sook

AU - Song, Hong Ji

AU - Lee, Joongyub

AU - Yang, Bo Ram

AU - Choi, Nam Kyong

AU - Park, Byung Joo

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