- 作者：Dimitrios Alexopoulos ; MD?/sup> ; dalex@med.upatras.gr ; Gerasimos Dimitropoulos ; MD?/sup> ; Periklis Davlouros ; MD?/sup> ; Ioanna Xanthopoulou ; MD?/sup> ; George Kassimis ; MD?/sup> ; Eleana F. Stavrou ; PhD&dagger ; ; George Hahalis ; MD?/sup> ; Aglaia Athanassiadou ; PhD&dagger ;
- 关键词：CYP2C19 ; high-dose clopidogrel ; pharmacogenetics ; platelet reactivity ; prasugrel
- 刊名：JACC: Cardiovascular Interventions
- 出版年：2011
- 出版时间：April 2011
- 年：2011
- 卷：4
- 期：4
- 页码：403-410
- 全文大小：917 K
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 VerifyNow 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 [CI]: 111.1 to 147.7 versus 201.7, 95 % CI: 183.2 to 220.2; p < 0.001). The least-squares mean difference between the 2 treatments was ?22.9 (95 % CI: ?66.7 to ?9.2, p < 0.001), and ?7.5 (95 % CI: ?9.5 to ?5.4, 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); )