CYP3A4 Genetic Status May Be Associated With Increased Vulnerability to the Inhibitory Effect of Calcium-Channel Blockers on Clopidogrel
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概要
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Background: Calcium-channel blockers (CCBs) inhibit the CYP3A4 enzyme, which is involved in clopidogrel activation. Studies have shown conflicting results regarding the effect of concomitant CCB administration on clopidogrel response. We investigated the relationship between CYP3A4 genotype and the inhibitory effect of CCBs on clopidogrel response. Methods and Results: Clopidogrel on-treatment platelet reactivity (OPR) was measured and CYP3A4 (IVS10+12G>A) genotyped in 1,247 consecutive patients with drug-eluting stent implantation. The mean OPR was 231±83 (P2Y12 reaction units: PRU). In total, 332 (26.6%) CCB users had higher OPR compared with 915 (73.4%) non-CCB users (245±84 vs. 227±83 PRU, P=0.001). The distribution of CYP3A4 (IVS10+12G>A) genotype was 63.6%, 32.6% and 3.8% for GG, GA and AA genotypes, respectively. After adjustment for possible confounding factors, the number of A-alleles was associated with increased vulnerability to CCB use (effect of CCB use ΔPRU: +8 PRU, P=0.210, +24 PRU, P=0.012, +50 PRU, P=0.025, for patients with 0, 1, and 2 A-alleles, respectively, +24 PRU, P=0.005 for GA/AA genotypes). Furthermore, only in the GA/AA-genotype did CCB use result in a significantly increased risk for high-OPR (odds ratio 1.84, 95% confidence interval 1.15–2.92, P=0.010). Conclusions: CCB use is associated with increased OPR. The number of CYP3A4 (IVS10+12G>A) A-alleles may be associated with an increased vulnerability to the effects of CCBs on clopidogrel response variation. (Circ J 2013; 77: 1289–1296)
著者
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KANG Hyun-Jae
Department of Internal Medicine and Cardiovascular Center, Seoul National University Hospital
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KOO Bon-Kwon
Department of Internal Medicine and Cardiovascular Center, Seoul National University Hospital
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KIM Hyo-Soo
Department of Internal Medicine and Cardiovascular Center, Seoul National University Hospital
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Lee Hae-young
Department Of Internal Medicine And Cardiovascular Center Seoul National University Hospital
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Park Young-bae
Department Of Internal Medicine College Of Medicine Scoul National University
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Ahn Hyo
Department Of Dermatology Korea University College Of Medicine
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Park Kyung
Depart. Of Oncology Yonsei Univ. Wonju College Of Medicine
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LEE Sang
Department of Acupuncture & Moxibustion, College of Oriental Medicine, Kyung Hee University
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Park Jin
Department of Advanced Materials Science and Engineering, Sungkyunkwan University, Suwon, Gyeonggi 440-746, Republic of Korea
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Oh Byung-Hee
Department of Internal Medicine and Cardiovascular Center, Seoul National University Hospital
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Yang Han-Mo
Department of Internal Medicine and Cardiovascular Center, Seoul National University Hospital
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Han Jung-Kyu
Department of Internal Medicine and Cardiovascular Center, Seoul National University Hospital
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Kang Jeehoon
Department of Internal Medicine and Cardiovascular Center, Seoul National University Main Hospital
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Kang Si-Hyuck
Department of Internal Medicine and Cardiovascular Center, Seoul National University Main Hospital
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Koh Jin-Sin
Department of Internal Medicine and Cardiovascular Center, Seoul National University Hospital
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Jeon Ki-Hyun
Department of Internal Medicine and Cardiovascular Center, Seoul National University Hospital
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Kang Jeehoon
Department of Internal Medicine and Cardiovascular Center, Seoul National University Hospital
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Kang Si-Hyuck
Department of Internal Medicine and Cardiovascular Center, Seoul National University Hospital
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Park Young-Bae
Department of Internal Medicine and Cardiovascular Center, Seoul National University Hospital
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Ahn Hyo
Department of Internal Medicine and Cardiovascular Center, Seoul National University Hospital
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Lee Sang
Department of Internal Medicine and Cardiovascular Center, Seoul National University Hospital
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