Prasugrel Overcomes High On-Clopidogrel Platelet Reactivity Post-Stenting More Effectively Than High-Dose (150-mg) Clopidogrel The Importance of CYP2C19*2 Genotyping

被引：110

作者：

Alexopoulos, Dimitrios ^{[1
]}

Dimitropoulos, Gerasimos ^{[1
]}

Davlouros, Periklis ^{[1
]}

Xanthopoulou, Ioanna ^{[1
]}

Kassimis, George ^{[1
]}

Stavrou, Eleana F. ^{[2
]}

Hahalis, George ^{[1
]}

Athanassiadou, Aglaia ^{[2
]}

机构：

[1] Patras Univ Hosp, Dept Cardiol, Patras 26500, Greece

[2] Univ Patras, Sch Med, Dept Gen Biol, GR-26110 Patras, Greece

来源：

JACC-CARDIOVASCULAR INTERVENTIONS | 2011年 / 4卷 / 04期

关键词：

CYP2C19; high-dose clopidogrel; pharmacogenetics; platelet reactivity; prasugrel; PERCUTANEOUS CORONARY INTERVENTION; OF-FUNCTION POLYMORPHISM; ASPIRIN-TREATED PATIENTS; TIMI; 38; TRIAL; ARTERY-DISEASE; ANTIPLATELET THERAPY; CYP2C19; GENOTYPE; DOUBLE-BLIND; CARE ASSAY; INHIBITION;

D O I：

10.1016/j.jcin.2010.12.011

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Objectives The primary aim of the study was to determine the antiplatelet effects of prasugrel versus high-dose clopidogrel in patients with high on-treatment platelet reactivity (HTPR) after percutaneous coronary intervention (PCI) and, secondarily, their relation to cytochrome (CYP) 2C19*2 carriage. Background High on-treatment platelet reactivity after clopidogrel administration after PCI is linked to the loss-of-function CYP2C19*2 allele and accompanied by an increased risk of adverse events. Methods We performed a prospective, randomized, single-blind, crossover study of platelet inhibition by prasugrel 10 mg/day versus high-dose 150 mg/day clopidogrel in 71 (of 210 screened; 33.8%) post-PCI patients with HTPR. Platelet function was assessed by the Verify Now assay (Accumetrics, San Diego, California), and real-time polymerase chain reaction genotyping was performed for CYP2C19*2 carriage. Results The primary endpoint of platelet reactivity (measured in platelet reactivity units) at the end of the 2 treatment periods was lower after prasugrel compared with clopidogrel (least-squares estimates 129.4, 95% confidence interval [Cl]: 111.1 to 147.7 versus 201.7, 95% Cl: 183.2 to 220.2; p < 0.001). The least-squares mean difference between the 2 treatments was -122.9 (95% Cl: -166.7 to -79.2, p < 0.001), and -47.5 (95% Cl: -79.5 to -15.4, p = 0.004), in carriers and noncarriers of at least 1 mutant allele, respectively. The HTPR rates were lower for prasugrel than for clopidogrel, in all patients (7.5% vs. 35.8%, p < 0.001), in carriers (5.3% vs. 47.4%, p = 0.007), and in noncarriers (8.8% vs. 29.4%, p = 0.005), respectively. Conclusions In patients with HTPR after PCI, prasugrel is more effective compared with high clopidogrel in reducing platelet reactivity, particularly in CYP2C19*2 carriers. Genotyping guidance might be helpful only in case an increased clopidogrel maintenance dose is considered. (Prasugrel Versus High Dose Clopidogrel in Clopidogrel Resistant Patients Post Percutaneous Coronary Intervention (PCI); NCT01109784) (J Am Coll Cardiol Intv 2011;4:403-10) (C) 2011 by the American College of Cardiology Foundation

引用

页码：403 / 410

页数：8

共 36 条

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