کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2948716 1577290 2010 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Clopidogrel Loading Dose Adjustment According to Platelet Reactivity Monitoring in Patients Carrying the 2C19*2Loss of Function Polymorphism
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی کاردیولوژی و پزشکی قلب و عروق
پیش نمایش صفحه اول مقاله
Clopidogrel Loading Dose Adjustment According to Platelet Reactivity Monitoring in Patients Carrying the 2C19*2Loss of Function Polymorphism
چکیده انگلیسی

ObjectivesWe aimed to investigate the biological impact of a tailored clopidogrel loading dose (LD) according to platelet reactivity monitoring in carriers of the cytochrome (CYP) 2C19*2loss-of-function polymorphism undergoing percutaneous coronary intervention for an acute coronary syndromes.BackgroundCYP2C19*2polymorphism is associated with reduced clopidogrel metabolism and a worse prognosis after percutaneous coronary intervention.MethodA prospective multicenter study enrolling 411 patients with non–ST-segment elevation acute coronary syndrome undergoing percutaneous coronary intervention was performed. Platelet reactivity was measured using the vasodilator-stimulated phosphoprotein (VASP) index, and a cutoff value of ≥50% was used to define high on-treatment platelet reactivity (HTPR). The genetic polymorphism of CYP2C19was determined by allele-specific polymerase chain reaction. In patients carrying CYP2C19*2and exhibiting HTPR after a first 600-mg LD of clopidogrel, dose adjustment was performed by using up to 3 additional 600 mg LDs to obtain a VASP index <50%.ResultsOne hundred thirty-four patients (35.3%) carried at least one 2C19*2allele (11 homozygotes [2.7%] and 123 heterozygotes [32.6%]). The VASP index in these patients was significantly higher than in homozygotic patients for the wild-type alleles (61.7 ± 18.4% vs. 49.2 ± 24.2%; p < 0.001). Of the 134 carriers of the loss-of-function polymorphism, 103 were considered to have HTPR. After a second clopidogrel LD, the VASP index was significantly decreased in these patients (69.7 ± 10.1% vs. 50.6 ± 17.6%; p < 0.0001). Finally, dose adjustment according to platelet reactivity monitoring, enabled 88% of 2C19*2carriers exhibiting HTPR to reach a VASP index <50%.ConclusionsIncreased and tailored clopidogrel loading dose according to platelet reactivity monitoring overcome HTPR in carriers of the loss-of-function CYP2C19*2polymorphism.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of the American College of Cardiology - Volume 56, Issue 20, 9 November 2010, Pages 1630–1636
نویسندگان
, , , , , , , , , , , , ,