TY - JOUR
T1 - High on-treatment platelet reactivity by ADP and increased risk of MACE in good clopidogrel metabolizers
AU - Marcucci, Rossella
AU - Giusti, Betti
AU - Paniccia, Rita
AU - Gori, Anna Maria
AU - Saracini, Claudia
AU - Valente, Serafina
AU - Giglioli, Cristina
AU - Parodi, Guido
AU - Antoniucci, David
AU - Gensini, Gian Franco
AU - Abbate, Rosanna
PY - 2012/12
Y1 - 2012/12
N2 - High on-treatment platelet reactivity (HPR) by ADP, which primarily reflects the effect of thienopyridines, has been found to be an independent predictor of ischemic events in patients with acute coronary syndrome (ACS) on dual antiplatelet therapy. CYP2C19*2 is associated with HPR by ADP. The aim of our study was to evaluate if high on-clopidogrel platelet reactivity (HPR) by ADP is associated with an increased risk of major adverse coronary events (MACE) after ACS independent of CYP2C19*2 allele, i.e. whether genotyping patients for CYP2C19*2 polymorphism is sufficient to identify those to be switched to novel antiplatelets. A total of 1187 patients were included (CYP2C19 *1/*1 n892; *1/*2 n264; *2/*2 n31); 76 MACE (CV death and non-fatal MI) were recorded in non-carriers of CYP2C19*2 (8.5) and 39 in carriers of CYP2C19*2 (13.2). At the landmark analysis in the first 6 months, HPR by ADP and CYP2C19*2 allele were both significantly and independently associated with MACE [HPR by ADP: HR2.0 (95 CI 1.23.4), p0.01; CYP2C19*2 allele: HR2.3 (95 CI 1.33.9), p0.003]. At the land mark analysis from 7 to 12 months, only HPR by ADP remained significantly associated with the risk of MACE [HPR by ADP: HR2.7 (95 CI 1.45.3), p0.003; CYP2C19*2: HR0.8 (95 CI 0.21.1), pns]. CYP2C19*2 allele and HPR by ADP are both independently associated with an increased risk of MACE in the first 6 months after ACS. HPR by ADP is associated with an increased risk until 12 months of follow-up. Therefore, both phenotype and genotype are clinically relevant for the evaluation of the antiplatelet effect of clopidogrel and for the prognostic stratification of ACS patients.
AB - High on-treatment platelet reactivity (HPR) by ADP, which primarily reflects the effect of thienopyridines, has been found to be an independent predictor of ischemic events in patients with acute coronary syndrome (ACS) on dual antiplatelet therapy. CYP2C19*2 is associated with HPR by ADP. The aim of our study was to evaluate if high on-clopidogrel platelet reactivity (HPR) by ADP is associated with an increased risk of major adverse coronary events (MACE) after ACS independent of CYP2C19*2 allele, i.e. whether genotyping patients for CYP2C19*2 polymorphism is sufficient to identify those to be switched to novel antiplatelets. A total of 1187 patients were included (CYP2C19 *1/*1 n892; *1/*2 n264; *2/*2 n31); 76 MACE (CV death and non-fatal MI) were recorded in non-carriers of CYP2C19*2 (8.5) and 39 in carriers of CYP2C19*2 (13.2). At the landmark analysis in the first 6 months, HPR by ADP and CYP2C19*2 allele were both significantly and independently associated with MACE [HPR by ADP: HR2.0 (95 CI 1.23.4), p0.01; CYP2C19*2 allele: HR2.3 (95 CI 1.33.9), p0.003]. At the land mark analysis from 7 to 12 months, only HPR by ADP remained significantly associated with the risk of MACE [HPR by ADP: HR2.7 (95 CI 1.45.3), p0.003; CYP2C19*2: HR0.8 (95 CI 0.21.1), pns]. CYP2C19*2 allele and HPR by ADP are both independently associated with an increased risk of MACE in the first 6 months after ACS. HPR by ADP is associated with an increased risk until 12 months of follow-up. Therefore, both phenotype and genotype are clinically relevant for the evaluation of the antiplatelet effect of clopidogrel and for the prognostic stratification of ACS patients.
KW - 2 polymoprhism
KW - Acute coronary syndrome
KW - Cardiovascular death
KW - Clopidogrel
KW - CYP2C19
KW - High on-treatment platelet reactivity
KW - Non-fatal myocardial infarction
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U2 - 10.3109/09537104.2012.658106
DO - 10.3109/09537104.2012.658106
M3 - Article
C2 - 22390861
AN - SCOPUS:84866974727
VL - 23
SP - 586
EP - 593
JO - Platelets
JF - Platelets
SN - 0953-7104
IS - 8
ER -