Meta-Analysis Appraising High Maintenance Dose Clopidogrel in Patients Who Underwent Percutaneous Coronary Intervention With and Without High On-Clopidogrel Platelet Reactivity

2015 ◽  
Vol 115 (5) ◽  
pp. 592-601 ◽  
Author(s):  
Wenfang Ma ◽  
Yan Liang ◽  
Jun Zhu ◽  
Yang Wang ◽  
Xinjie Wang
Keyword(s):  
Percutaneous Coronary Intervention ◽  
Maintenance Dose ◽  
Platelet Reactivity ◽  
Meta Analysis ◽  
Coronary Intervention ◽  
Percutaneous Coronary

scholarly journals Effect of CYP3A4*22 and PPAR-α Genetic Variants on Platelet Reactivity in Patients Treated with Clopidogrel and Lipid-Lowering Drugs Undergoing Elective Percutaneous Coronary Intervention

Genes ◽  
2020 ◽  
Vol 11 (9) ◽  
pp. 1068
Author(s):  
Thomas Bergmeijer ◽  
Alfi Yasmina ◽  
Gerrit Vos ◽  
Paul Janssen ◽  
Christian Hackeng ◽  
...  
Keyword(s):  
Percutaneous Coronary Intervention ◽  
Genetic Variants ◽  
Platelet Reactivity ◽  
Meta Analysis ◽  
Statistical Significance ◽  
Coronary Intervention ◽  
Lipid Lowering ◽  
Study Cohort ◽  
Elective Percutaneous Coronary Intervention ◽  
Percutaneous Coronary

This study aims to determine whether genetic variants that influence CYP3A4 expression are associated with platelet reactivity in clopidogrel-treated patients undergoing elective percutaneous coronary intervention (PCI), and to evaluate the influence of statin/fibrate co-medication on these associations. A study cohort was used containing 1124 consecutive elective PCI patients in whom CYP3A4*22 and PPAR-α (G209A and A208G) SNPs were genotyped and the VerifyNow P2Y12 platelet reactivity test was performed. Minor allele frequencies were 0.4% for CYP3A4*22/*22, 6.8% for PPAR-α G209A AA, and 7.0% for PPAR-α A208G GG. CYP3A4*22 was not associated with platelet reactivity. The PPAR-α genetic variants were significantly associated with platelet reactivity (G209A AA: −24.6 PRU [−44.7, −4.6], p = 0.016; A208G GG: −24.6 PRU [−44.3, −4.8], p = 0.015). Validation of these PPAR-α results in two external cohorts, containing 716 and 882 patients, respectively, showed the same direction of effect, although not statistically significant. Subsequently, meta-analysis of all three cohorts showed statistical significance of both variants in statin/fibrate users (p = 0.04 for PPAR-a G209A and p = 0.03 for A208G), with no difference in statin/fibrate non-users. In conclusion, PPAR-α G209A and A208G were associated with lower platelet reactivity in patients undergoing elective PCI who were treated with clopidogrel and statin/fibrate co-medication. Further research is necessary to confirm these findings.

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