Differential Impact of Clinical and Genetic Factors on High Platelet Reactivity in Patients with Coronary Artery Disease Treated with Clopidogrel and Prasugrel

• Published in: Journal of Atherosclerosis and Thrombosis 2022/07/01, Vol.29(7), pp.1031-1039
• Main Authors: Saito, Yuichi, Nishi, Takeshi, Wakabayashi, Shinichi, Ohno, Yuji, Kitahara, Hideki, Ariyoshi, Noritaka, Kobayashi, Yoshio
• Format: Article
• Language: English
• Subjects: Blood Platelets; Clopidogrel; Clopidogrel - therapeutic use; Coronary Artery Disease - drug therapy; Coronary Artery Disease - genetics; Cytochrome P-450 CYP2C19 - genetics; Diabetes Mellitus - drug therapy; Genetic testing; Humans; Original; P2Y12 inhibitor; Percutaneous Coronary Intervention - adverse effects; Platelet Aggregation Inhibitors - adverse effects; Platelet Function Tests; Prasugrel; Prasugrel Hydrochloride - therapeutic use; Prospective Studies; Renal Insufficiency, Chronic - etiology; Risk factors; Ticlopidine - pharmacology
• ISSN: 1340-3478; 1880-3873; 1880-3873
• DOI: 10.5551/jat.63035

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.