Analysis of the risk factors of clopidogrel response in a Han Chinese population undergoing percutaneous coronary intervention

Background Clopidogrel is an antiplatelet drug, which requires the effiux pump P-glycoprotein （multidrug resistance-1, MDR1） encoded by the ABCB1 gene for intestinal absorption. However, recent studies evaluating the relationship between ABCB 1 genetic polymorphisms and clopidogrel response have shown conflicting results due to both genetic and non-genetic factors. This study aimed to analyze the risk factors of clopidogrel response in a Han Chinese population undergoing percutaneous coronary intervention （PCI）. Methods A total of 520 Han Chinese patients with coronary artery disease undergoing planned drug-eluting stent placement and receiving dual-antiplatelet therapy were sequentially recruited and followed up for 1 year. The effects of clinical risk fac- tors and ABCB1 genetic polymorphisms on major adverse cardiovascular events （MACE） within 1 year or bleeding within 6 months after PCI were assessed. Results The patients were comprised of 82% men and 40% smokers. Diabetes, hypertension and low ejection fraction were associated with higher risk of MACE within 1 year after PCI. The hazard ratios [HR] and 95% confidence intervals [CI] were 3.15 [1.46-6.78], 2.78 [1.51-5.10] and 0.98[0.95-1.00], respectively. Diabetes and female were also significantly associated with bleeding risk within 6 months （odds ratio [OR] [95%CI]： 1.96 [1.11-3.44] and 2.20 [1.20-4.05]. Use of angiotensin-converting enzyme inhibitors （ACEIs） was associated with a low risk of bleeding events （OR [95%CI]： 0.53 [0.31-0.91]）. There was no significant impact of ABCB1 c.1236 C〉T, ABCB1 c.2677 G〉T/A, or ABCB1 c.3435 C〉T on the risk of MACE within 1 year or occurrence of bleeding within 6 months after PCI. Conclusions These results suggest a lack of association between ABCB1 genetic variants and adverse cardiovascular outcomes. However, diabetes, hypertension and low ejection fraction are high risk factors of MACE. In addition, diabetes and female are a high risk of bleeding, which can be reduced by use of ACEIs.