PMID- 24440142
OWN - NLM
STAT- MEDLINE
DCOM- 20150109
LR  - 20181202
IS  - 1879-2472 (Electronic)
IS  - 0049-3848 (Linking)
VI  - 133
IP  - 4
DP  - 2014 Apr
TI  - Impact of CYP2C19 polymorphism and proton pump inhibitors on platelet reactivity 
      to clopidogrel and clinical outcomes following stent implantation.
PG  - 599-605
LID - S0049-3848(14)00012-7 [pii]
LID - 10.1016/j.thromres.2014.01.003 [doi]
AB  - BACKGROUND: The response to clopidogrel, and some kind of the drug interaction 
      are multifactorial. METHODS AND RESULTS: We enrolled 174 consecutive patients and 
      determined CYP2C19 genotypes, measured platelet aggregation, and assessed the 
      relationship between CYP2C19 genotype and platelet reactivity 24hours after 
      clopidogrel administration, and the risk of cardiovascular events over 18months 
      follow-up. A sub analysis examined the impact of rabeprazole, a proton pump 
      inhibitor (PPI) less affected by CYP2C19. The CYP2C19 genotype was extensive 
      metabolizer (EM) in 36%, intermediate metabolizer (IM) in 45%, and poor 
      metabolizer (PM) in 19%. Platelet reactivity was significantly lower in the EM 
      group than in the IM and PM groups (EM, IM, PM: 3560+/-1404, 4203+/-1302, 
      5084+/-1007AU*min, P<0.05). The cardiovascular event rate was higher in the IM and 
      PM groups than in the EM group (12.7% and 12.5% vs 1.6%; Hazard ratio for IM 
      10.6, P=0.029; for PM 11.3, P=0.040). No differences were seen between patients 
      taking (N=50) and not taking (N=124) rabeprazole in residual platelet aggregation 
      (4407+/-1360 vs 4048+/-1394, AU*min, P=0.2782), or in cardiovascular events (10.0% vs 
      8.1%, HR 0.97, P=0.97). CONCLUSIONS: CYP2C19 genotype is associated with an 
      increased risk of cardiovascular events following stent implantation in Japanese 
      patients.
CI  - Copyright (c) 2013 Elsevier Ltd. All rights reserved.
FAU - Hokimoto, Seiji
AU  - Hokimoto S
AD  - Department of Cardiovascular Medicine, Graduate School of Medical Sciences, 
      Kumamoto University, Kumamoto, Japan. Electronic address: 
      shokimot@kumamoto-u.ac.jp.
FAU - Mizobe, Michio
AU  - Mizobe M
AD  - Department of Cardiovascular Medicine, Graduate School of Medical Sciences, 
      Kumamoto University, Kumamoto, Japan.
FAU - Akasaka, Tomonori
AU  - Akasaka T
AD  - Department of Cardiovascular Medicine, Graduate School of Medical Sciences, 
      Kumamoto University, Kumamoto, Japan.
FAU - Arima, Yuichiro
AU  - Arima Y
AD  - Department of Cardiovascular Medicine, Graduate School of Medical Sciences, 
      Kumamoto University, Kumamoto, Japan.
FAU - Kaikita, Koichi
AU  - Kaikita K
AD  - Department of Cardiovascular Medicine, Graduate School of Medical Sciences, 
      Kumamoto University, Kumamoto, Japan.
FAU - Nakagawa, Kazuko
AU  - Nakagawa K
AD  - Division of Pharmacology and Therapeutics, Graduate School of Medical and 
      Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan.
FAU - Ogawa, Hisao
AU  - Ogawa H
AD  - Department of Cardiovascular Medicine, Graduate School of Medical Sciences, 
      Kumamoto University, Kumamoto, Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140109
PL  - United States
TA  - Thromb Res
JT  - Thrombosis research
JID - 0326377
RN  - 32828355LL (Rabeprazole)
RN  - A74586SNO7 (Clopidogrel)
RN  - EC 1.14.14.1 (CYP2C19 protein, human)
RN  - EC 1.14.14.1 (Cytochrome P-450 CYP2C19)
RN  - OM90ZUW7M1 (Ticlopidine)
SB  - IM
MH  - Aged
MH  - Blood Platelets/*drug effects/enzymology
MH  - Cardiovascular Diseases/blood/enzymology/*etiology/genetics
MH  - Clopidogrel
MH  - Cytochrome P-450 CYP2C19/*administration & dosage
MH  - Drug Interactions
MH  - Female
MH  - Genotype
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Percutaneous Coronary Intervention/*methods
MH  - Platelet Aggregation/drug effects/genetics
MH  - Polymorphism, Genetic
MH  - Rabeprazole/*administration & dosage
MH  - *Stents
MH  - Ticlopidine/administration & dosage/*analogs & derivatives
OTO - NOTNLM
OT  - Antiplatelet therapy
OT  - Clopidogrel, Proton pump inhibitor, Coronary artery disease
OT  - Percutaneous coronary intervention
OT  - Polymorphism
EDAT- 2014/01/21 06:00
MHDA- 2015/01/13 06:00
CRDT- 2014/01/21 06:00
PHST- 2013/09/07 00:00 [received]
PHST- 2013/11/09 00:00 [revised]
PHST- 2014/01/03 00:00 [accepted]
PHST- 2014/01/21 06:00 [entrez]
PHST- 2014/01/21 06:00 [pubmed]
PHST- 2015/01/13 06:00 [medline]
AID - S0049-3848(14)00012-7 [pii]
AID - 10.1016/j.thromres.2014.01.003 [doi]
PST - ppublish
SO  - Thromb Res. 2014 Apr;133(4):599-605. doi: 10.1016/j.thromres.2014.01.003. Epub 
      2014 Jan 9.