Yuichi Saito1, Takeshi Nishi1,2, Shinichi Wakabayashi1,3, Yuji Ohno1,4, Hideki Kitahara1, Noritaka Ariyoshi5, Yoshio Kobayashi1. 1. Department of Cardiovascular Medicine, Chiba University Graduate School of Medicine. 2. Division of Cardiovascular Medicine, Stanford University School of Medicine and Stanford Cardiovascular Institute. 3. Department of Cardiology, Eastern Chiba Medical Center. 4. Department of Cardiovascular Medicine, Narita Red Cross Hospital. 5. Department of Personalized Medicine and Preventive Healthcare Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University.
Abstract
AIM: High platelet reactivity (HPR) is associated with increased risks of thrombotic events in patients with coronary artery disease. The recently developed ABCD-GENE score identified five clinical and genetic factors (age, body mass index, chronic kidney disease, diabetes, and the CYP2C19 loss-of-function allele) for HPR, although the significance of various stages of each factor is unclear. METHODS: Four prospective studies were pooled, in which platelet reactivity was measured using the VerifyNow assay with clopidogrel and prasugrel; genotyping of CYP2C19 was also performed. Each component of the ABCD-GENE score was divided into three subcategories. VerifyNow P2Y12 reactivity units ＞208 were defined as HPR. RESULTS: A total of 184 patients were included, of which 111 (60%) and 51 (28%) had HPR with clopidogrel and prasugrel. Chronic kidney disease had an impact on HPR on both clopidogrel and prasugrel, whereas the impact of diabetes was more evident in patients treated with prasugrel. Although the number of CYP2C19 loss-of-function alleles was clearly associated with a likelihood of HPR with clopidogrel, P2Y12 reactivity units with prasugrel treatment were also significantly and progressively higher in patients with more CYP2C19 loss-of-function alleles. CONCLUSIONS: Clinical and genetic factors had a differential effect on a P2Y12 inhibitor reactivity with clopidogrel and prasugrel in patients with coronary artery disease. The severity of the factors also had a different impact on HPR.
AIM: High platelet reactivity (HPR) is associated with increased risks of thrombotic events in patients with coronary artery disease. The recently developed ABCD-GENE score identified five clinical and genetic factors (age, body mass index, chronic kidney disease, diabetes, and the CYP2C19 loss-of-function allele) for HPR, although the significance of various stages of each factor is unclear. METHODS: Four prospective studies were pooled, in which platelet reactivity was measured using the VerifyNow assay with clopidogrel and prasugrel; genotyping of CYP2C19 was also performed. Each component of the ABCD-GENE score was divided into three subcategories. VerifyNow P2Y12 reactivity units ＞208 were defined as HPR. RESULTS: A total of 184 patients were included, of which 111 (60%) and 51 (28%) had HPR with clopidogrel and prasugrel. Chronic kidney disease had an impact on HPR on both clopidogrel and prasugrel, whereas the impact of diabetes was more evident in patients treated with prasugrel. Although the number of CYP2C19 loss-of-function alleles was clearly associated with a likelihood of HPR with clopidogrel, P2Y12 reactivity units with prasugrel treatment were also significantly and progressively higher in patients with more CYP2C19 loss-of-function alleles. CONCLUSIONS: Clinical and genetic factors had a differential effect on a P2Y12 inhibitor reactivity with clopidogrel and prasugrel in patients with coronary artery disease. The severity of the factors also had a different impact on HPR.
Authors: Daniel M F Claassens; Gerrit J A Vos; Thomas O Bergmeijer; Renicus S Hermanides; Arnoud W J van 't Hof; Pim van der Harst; Emanuele Barbato; Carmine Morisco; Richard M Tjon Joe Gin; Folkert W Asselbergs; Arend Mosterd; Jean-Paul R Herrman; Willem J M Dewilde; Paul W A Janssen; Johannes C Kelder; Maarten J Postma; Anthonius de Boer; Cornelis Boersma; Vera H M Deneer; Jurriën M Ten Berg Journal: N Engl J Med Date: 2019-09-03 Impact factor: 91.245
Authors: Charlotte Grosdidier; Jacques Quilici; Marie Loosveld; Laurence Camoin; Pierre Julien Moro; Noémie Saut; Bénédicte Gaborit; Mathieu Pankert; William Cohen; Marc Lambert; Shirley Beguin; Pierre Emmanuel Morange; Jean-Louis Bonnet; Marie-Christine Alessi; Thomas Cuisset Journal: Am J Cardiol Date: 2013-01-19 Impact factor: 2.778