Antiplatelet effect of clopidogrel can be reduced by calcium-channel blockers.
OBJECTIVE
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.


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.


CONCLUSIONS
CCBs inhibit the antiplatelet activity of clopidogrel.
Department of Neurology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
Kwon-Duk
KD
Seo
Department of Neurology, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
Young Dae
YD
Kim
Cardiology Division, Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea. ; Severance Institute for Vascular and Metabolic Research, Yonsei University, Seoul, Korea.
Young-Won
YW
Yoon
Cardiology Division, Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
Jong-Youn
JY
Kim
Department of Neurology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea. ; Severance Institute for Vascular and Metabolic Research, Yonsei University, Seoul, Korea.
Kyung-Yul
KY
Lee
D000368:Aged; D000369:Aged, 80 and over; D001792:Blood Platelets / Q000187:drug effects*; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D000077144:Clopidogrel; D004095:Dihydropyridines / Q000627:therapeutic use*; D004347:Drug Interactions; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000627:therapeutic use
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D010975:Platelet Aggregation Inhibitors; C038806:1,4-dihydropyridine; D000077144:Clopidogrel; D013988:Ticlopidine
Calcium channel blockers; clopidogrel; platelet reactivity unit