Association of CYP2C19 Polymorphisms With Clopidogrel Reactivity and Clinical Outcomes in Chronic Ischemic Stroke.

Abstract

BACKGROUND:

CYP2C19variants are associated with the antiplatelet effects of clopidogrel against recurrent cardiovascular events. However, it remains unknown whether the elapsed time from stroke onset affects the relationship between the genetic variants and such events. To address this, we conducted a prospective cohort study to determine the effect ofCYP2C19variants on clinical outcomes in the chronic phase.Methods and Results:In total, 518 Japanese non-acute stroke patients treated with clopidogrel were registered at 14 institutions. Patients were classified into 3 clopidogrel-metabolizing groups according toCYP2C19genotype: extensive metabolizer (EM:*1/*1), intermediate metabolizer (IM:*1/*2or*1/*3), and poor metabolizer (PM:*2/*2,*2/*3, or*3/*3). Antiplatelet effects of clopidogrel were assessed by adenosine diphosphate (ADP)-induced platelet aggregation and vasodilator-stimulated phosphoprotein (VASP) phosphorylation. The endpoint was composite cerebrocardiovascular events (CVEs). In 501 successfully followed-up patients, the median time from index stroke to enrollment was 181 days. There were 28 cardiovascular and 2 major bleeding events. There were no significant differences in the rates of cardiovascular events among the groups.

CONCLUSIONS:

Despite associations betweenCYP2C19variants and on-clopidogrel platelet reactivity, there was no significant difference in rates of CVEs in the chronic stroke phase among the 3 clopidogrel-metabolizing groups ofCYP2C19variants.

• Authors: Tomotaka Tanaka, Hiroshi Yamagami, Masafumi Ihara, Toshiyuki Miyata, Shigeki Miyata, Toshimitsu Hamasaki, Shu Amano, Kazuki Fukuma, Haruko Yamamoto, Jyoji Nakagawara, Eisuke Furui, Shinichiro Uchiyama, Boohan Hyun, Yasumasa Yamamoto, Yasuhiro Manabe, Yasuhiro Ito, Ryuzo Fukunaga, Takeo Abumiya, Masahiro Yasaka, Kazuo Kitagawa, Kazunori Toyoda, Kazuyuki Nagatsuka
• Journal: Circulation journal : official journal of the Japanese Circulation Society (Circ J) Vol. 83 Issue 6 Pg. 1385-1393 (05 24 2019) ISSN: 1347-4820 [Electronic] Japan
• PMID: 31006731 (Publication Type: Clinical Trial, Journal Article, Multicenter Study)

Chemical References

• Clopidogrel
• CYP2C19 protein, human
• Cytochrome P-450 CYP2C19

Topics

• Aged
• Asian People
• Brain Ischemia (enzymology, genetics, pathology)
• Chronic Disease
• Clopidogrel (administration & dosage, pharmacokinetics)
• Cytochrome P-450 CYP2C19 (genetics, metabolism)
• Female
• Follow-Up Studies
• Humans
• Japan
• Male
• Middle Aged
• Polymorphism, Genetic
• Prospective Studies
• Stroke (enzymology, genetics, pathology)