Yonsei Med J.  2014 May;55(3):683-688. 10.3349/ymj.2014.55.3.683.

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

• Seo KD
• Kim YD
• Yoon YW
• Kim JY
• Lee KY

• KMID: 2068678
• DOI: http://doi.org/10.3349/ymj.2014.55.3.683

Abstract

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> or =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.
CONCLUSION
CCBs inhibit the antiplatelet activity of clopidogrel.

Keyword

Calcium channel blockers; clopidogrel; platelet reactivity unit

MeSH Terms

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/therapeutic use
Calcium Channel Blockers
Dihydropyridines
Platelet Aggregation Inhibitors
Ticlopidine

Figure

• 

  Fig. 1 Box-and-whisker plot showing PRU as determined by the VerifyNow P2Y12 assay in patients at baseline and after discontinuation of CCBs. Cut-off values of high post-treatment platelet reactivity to clopidogrel are indicated by dotted lines. PRU, P2Y12 reaction units; CCBs, calcium channel blockers.

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