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Antiplatelet Effect of Clopidogrel Can Be Reduced by Calcium-Channel Blockers

 Kwon-Duk Seo  ;  Young Dae Kim  ;  Young-Won Yoon  ;  Jong-Youn Kim  ;  Kyung-Yul Lee 
 YONSEI MEDICAL JOURNAL, Vol.55(3) : 683-688, 2014 
Journal Title
Issue Date
Aged ; Aged, 80 and over ; Blood Platelets/drug effects* ; Calcium Channel Blockers/therapeutic use* ; Dihydropyridines/therapeutic use* ; Drug Interactions ; Female ; Humans ; Male ; Middle Aged ; Platelet Aggregation Inhibitors/therapeutic use* ; Ticlopidine/analogs & derivatives* ; Ticlopidine/therapeutic use
Calcium channel blockers ; clopidogrel ; platelet reactivity unit
PURPOSE: Clopidogrel is metabolized by the hepatic cytochrome P450 (CYP) system into its active thiol metabolite. CYP3A4 is involved in the metabolism of both clopidogrel and dihydropyridine calcium channel blockers (CCBs). A few reports have suggested an inhibitory interaction between CCBs and clopidogrel. Accordingly, the aim of this study was to determine the effect of CCBs on the antiplatelet activity of clopidogrel by serial P2Y12 reaction unit (PRU) measurements. MATERIALS AND METHODS: We assessed changes in antiplatelet activity in patients receiving both clopidogrel and CCBs for at least 2 months prior to enrollment in the study. The antiplatelet activity of clopidogrel was measured by VerifyNow P2Y12 assay in the same patient while medicated with CCBs and at 8 weeks after discontinuation of CCBs. After discontinuation of the CCBs, angiotensin receptor blockers were newly administered to the patients or dosed up for control of blood pressure. RESULTS: Thirty patients finished this study. PRU significantly decreased after discontinuation of CCBs (238.1±74.1 vs. 215.0±69.3; p=0.001). Of the 11 patients with high post-treatment platelet reactivity to clopidogrel (PRU≥275), PRU decreased in nine patients, decreasing below the cut-off value in seven of these nine patients after 8 weeks. Decrease in PRU was not related to CYP2C19 genotype.
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1. College of Medicine (의과대학) > Dept. of Neurology (신경과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Young Dae(김영대) ORCID logo https://orcid.org/0000-0001-5750-2616
Seo, Kwon Duk(서권덕)
Yoon, Young Won(윤영원) ORCID logo https://orcid.org/0000-0002-0907-0350
Lee, Kyung Yul(이경열) ORCID logo https://orcid.org/0000-0001-5585-7739
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