Inhibitory interaction between calcium channel blocker and clopidogrel: Efficacy of cilostazol to overcome it

Seung Pyo Lee, Jang Whan Bae, Kyung Woo Park, Seung-Woon Rha, Jang Ho Bae, Jung Won Suh, In Ho Chae, Myeong Chan Cho, Hyo Soo Kim

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Background: The clinical effect of, and additive measures to overcome the possible inhibitory calcium channel blocker (CCB)-clopidogrel interaction in Asian patients undergoing percutaneous coronary intervention is unknown. Methods and Results: A total of 900 Korean patients enrolled for the multicenter, prospective, randomized Influence of CILostazol-based triple antiplatelet therapy ON ischemic complication after drug-eluting stenT implantation (CILON-T) trial were divided into 4 groups depending on CCB prescription and type of anti-platelet therapy (dual [DAT] vs. triple [TAT; addition of cilostazol to DAT]) in a 2×2 factorial manner. The primary endpoint was a composite of cardiac death, non-fatal myocardial infarction and ischemic stroke at 6 months after PCI. On-treatment platelet reactivity (OPR) was assessed on VerifyNow P2Y12 assay. Concomitant CCB use increased OPR in the DAT group (mean ± SEM: 251.2±7.6 vs. 225.6±5.1; P=0.008), but not in the TAT group (214.5±9.1 vs. 203.4±5.6; P=0.294). Primary endpoint increased by use of CCB in patients with DAT (4.9% vs. 0.9%, P=0.016), but not in those with TAT (0% vs. 1.8%, P=0.346). Addition of cilostazol to DAT reduced OPR and clinical events in patients taking CCB (P=0.007 for P2Y12 reaction units; P=0.027 for thrombotic events). CCB without concomitant cilostazol use was a significant predictor of total thrombotic events. Conclusions: Concomitant use of CCB may weaken the anti-platelet effect of clopidogrel and increase subsequent thrombotic events in Asian subjects. This hazardous CCB-clopidogrel interaction may be overcome by addition of cilostazol.

Original languageEnglish
Pages (from-to)2581-2589
Number of pages9
JournalCirculation Journal
Issue number11
Publication statusPublished - 2011 Oct 31



  • Calcium channel blocker
  • Cilostazol
  • Clopidogrel
  • Platelet function test
  • Thrombosis

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Lee, S. P., Bae, J. W., Park, K. W., Rha, S-W., Bae, J. H., Suh, J. W., Chae, I. H., Cho, M. C., & Kim, H. S. (2011). Inhibitory interaction between calcium channel blocker and clopidogrel: Efficacy of cilostazol to overcome it. Circulation Journal, 75(11), 2581-2589.