Document Detail


Platelet inhibition by adjunctive cilostazol versus high maintenance-dose clopidogrel in patients with acute myocardial infarction according to cytochrome P450 2C19 genotype.
MedLine Citation:
PMID:  21511217     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVES: The aim of this study was to assess the degree of platelet inhibition by adjunctive cilostazol in patients with acute myocardial infarction (AMI) according to hepatic cytochrome P450 2C19 (CYP2C19) genotype.
BACKGROUND: Although adjunctive cilostazol intensifies platelet inhibition in AMI patients, it is not established whether this regimen can be free from the effect of CYP2C19 loss-of-function variants (*2/*3).
METHODS: We randomly assigned 126 AMI patients with available CYP2C19 genotyping to receive adjunctive cilostazol (triple group; n = 64) or high maintenance-dose (MD) clopidogrel of 150 mg/day (high-MD group; n = 62). Using conventional aggregometry and VerifyNow (Accumetrics Inc., San Diego, California), platelet reactivity was measured at pre-discharge and 30-day follow-up. Primary endpoint was change in maximal platelet aggregation (ΔAgg(max)) between pre-discharge and 30-day follow-up. High on-treatment platelet reactivity (HPR) was defined as 20 μmol/l adenosine diphosphate-induced maximal platelet aggregation (Agg(max)) >59%.
RESULTS: In noncarriers, despite numerically greater inhibition by adjunctive cilostazol, changes in platelet measures and the rate of HPR did not significantly differ between the 2 groups. In carriers, ΔAgg(max) after 5 and 20 μmol/l adenosine diphosphate stimuli was significantly higher in the triple (n = 39) versus high-MD group (n = 38) (21.8 ± 13.9% vs. 9.0 ± 13.3%, p < 0.001, and 24.2 ± 17.2% vs. 7.7 ± 15.5%, p < 0.001, respectively). Likewise, changes in late platelet aggregation and P2Y12 reaction unit were consistently greater in the triple versus high-MD group. Fewer patients in the triple group met the criteria of HPR at 30-day follow-up than in the high-MD group (15.4% vs. 44.7%, p = 0.005).
CONCLUSIONS: Compared with high-MD clopidogrel, adjunctive cilostazol significantly enhances platelet inhibition and reduces the rate of HPR, especially in AMI patients with CYP2C19 loss-of-function variants. (Adjunctive Cilostazol Versus High Maintenance-Dose Clopidogrel in Acute Myocardial Infarction (AMI) Patients According to CYP2C19 Polymorphism [ACCELAMI2C19]; NCT00915733).
Authors:
In-Suk Kim; Young-Hoon Jeong; Yongwhi Park; Ki-Soo Park; Seong-Eun Yun; Jeong-Rang Park; Seok-Jae Hwang; Eun-Ha Koh; Choong Hwan Kwak; Jin-Yong Hwang; Sunjoo Kim
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Publication Detail:
Type:  Comparative Study; Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  JACC. Cardiovascular interventions     Volume:  4     ISSN:  1876-7605     ISO Abbreviation:  JACC Cardiovasc Interv     Publication Date:  2011 Apr 
Date Detail:
Created Date:  2011-04-22     Completed Date:  2011-08-15     Revised Date:  2014-09-05    
Medline Journal Info:
Nlm Unique ID:  101467004     Medline TA:  JACC Cardiovasc Interv     Country:  United States    
Other Details:
Languages:  eng     Pagination:  381-91     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
Data Bank Information
Bank Name/Acc. No.:
ClinicalTrials.gov/NCT00915733
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MeSH Terms
Descriptor/Qualifier:
Adenosine Diphosphate / diagnostic use
Aged
Angioplasty, Balloon, Coronary* / adverse effects
Aryl Hydrocarbon Hydroxylases / genetics,  metabolism*
Aspirin / administration & dosage
Chi-Square Distribution
Drug Therapy, Combination
Female
Genotype
Humans
Korea
Liver / enzymology*
Male
Middle Aged
Myocardial Infarction / blood,  therapy*
Phenotype
Platelet Aggregation / drug effects*
Platelet Aggregation Inhibitors / administration & dosage*,  adverse effects,  pharmacokinetics
Platelet Function Tests
Predictive Value of Tests
Regression Analysis
Risk Assessment
Risk Factors
Tetrazoles / administration & dosage*,  adverse effects,  pharmacokinetics
Thrombosis / blood,  etiology,  prevention & control
Ticlopidine / administration & dosage,  adverse effects,  analogs & derivatives*,  pharmacokinetics
Treatment Outcome
Chemical
Reg. No./Substance:
0/Platelet Aggregation Inhibitors; 0/Tetrazoles; 61D2G4IYVH/Adenosine Diphosphate; A74586SNO7/clopidogrel; EC 1.14.14.1/Aryl Hydrocarbon Hydroxylases; EC 1.14.14.1/CYP2C19 protein, human; N7Z035406B/cilostazol; OM90ZUW7M1/Ticlopidine; R16CO5Y76E/Aspirin
Comments/Corrections
Comment In:
JACC Cardiovasc Interv. 2011 Apr;4(4):411-4   [PMID:  21511220 ]

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