Yajing Zhai1, Hairong He2, Xiancang Ma2, Jiao Xie1, Ti Meng1, Yalin Dong3, Jun Lu4. 1. Department of Pharmacy, The First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, People's Republic of China. 2. Clinical Research Center, The First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, People's Republic of China. 3. Department of Pharmacy, The First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, People's Republic of China. dongyalin@mail.xjtu.edu.cn. 4. Clinical Research Center, The First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, People's Republic of China. lujun2006@mail.xjtu.edu.cn.
Abstract
PURPOSE: The substantial variability in the antiplatelet efficacy of clopidogrel has raised major concerns. Molecular epidemiological research suggests that ABCB1 C3435T polymorphism may be associated with clopidogrel response, but results remain controversial. To derive a more precise evaluation of the associations between ABCB1 C3435T polymorphism and the clinical efficacy of clopidogrel, we have conducted a PRISMA-compliant meta-analysis. METHODS: The PubMed and EMBASE databases were searched for eligible studies up to 25 October 2016. The odds ratio (OR), the standard mean difference (SMD) and 95% confidence interval (CI) were applied to assess the strength of the relationship. RESULTS: Overall, 28 related studies involving 23,243 patients were analyzed. No association was found between the ABCB1 polymorphisms and the primary outcome. In the subgroup analysis, the C3435T mutation significantly reduced platelet activity as tested by the LTA assay in the dominant (SMD -0.140, 95% CI -0.272 to -0.009, P = 0.036) and heterozygous (SMD -0.154, 95% CI -0.290 to -0.017, P = 0.027) models, but the result lacked robustness in the sensitivity analysis. A significant association between the C3435T polymorphism and bleeding risk was also observed with low heterogeneity in the dominant (OR 1.805, 95% CI1.124-2.900, P =0.015, I 2 = 0%), homozygous (OR 1.952, 95% CI 1.055-3.611, P = 0.033, I 2 = 13.2%) and heterozygous (OR 1.793, 95% CI 1.091-2.946, P = 0.021, I 2 = 0%) models in Asian patients. CONCLUSIONS: The results of the meta-analysis suggest that ABCB1 C3435T polymorphism may increase the risk of bleeding in Asian patients treated with clopidogrel. The implied relationship needs to be verified in future basic genetic pharmacology studies.
PURPOSE: The substantial variability in the antiplatelet efficacy of clopidogrel has raised major concerns. Molecular epidemiological research suggests that ABCB1C3435T polymorphism may be associated with clopidogrel response, but results remain controversial. To derive a more precise evaluation of the associations between ABCB1C3435T polymorphism and the clinical efficacy of clopidogrel, we have conducted a PRISMA-compliant meta-analysis. METHODS: The PubMed and EMBASE databases were searched for eligible studies up to 25 October 2016. The odds ratio (OR), the standard mean difference (SMD) and 95% confidence interval (CI) were applied to assess the strength of the relationship. RESULTS: Overall, 28 related studies involving 23,243 patients were analyzed. No association was found between the ABCB1 polymorphisms and the primary outcome. In the subgroup analysis, the C3435T mutation significantly reduced platelet activity as tested by the LTA assay in the dominant (SMD -0.140, 95% CI -0.272 to -0.009, P = 0.036) and heterozygous (SMD -0.154, 95% CI -0.290 to -0.017, P = 0.027) models, but the result lacked robustness in the sensitivity analysis. A significant association between the C3435T polymorphism and bleeding risk was also observed with low heterogeneity in the dominant (OR 1.805, 95% CI1.124-2.900, P =0.015, I 2 = 0%), homozygous (OR 1.952, 95% CI 1.055-3.611, P = 0.033, I 2 = 13.2%) and heterozygous (OR 1.793, 95% CI 1.091-2.946, P = 0.021, I 2 = 0%) models in Asian patients. CONCLUSIONS: The results of the meta-analysis suggest that ABCB1C3435T polymorphism may increase the risk of bleeding in Asian patients treated with clopidogrel. The implied relationship needs to be verified in future basic genetic pharmacology studies.
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