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Risk of stroke in CYP2C19 LoF polymorphism carrier coronary artery disease patients undergoing clopidogrel therapy: An ethnicity-based updated meta-analysis

      Highlights

      • Treatment with clopidogrel may induce stroke recurrence in CYP2C19 LoF carriers.
      • High dose of clopidogrel shows secondary outcomes in poor metabolizer CAD patients.
      • Asian CYP2C19*2/*3 carrier population has a significantly higher risk of stroke.
      • Increasing doses of clopidogrel do not reduce risk in polymorphism carrier patients.
      • Caucasian, Hispanic and other ethnic populations show significant risk association.

      Abstract

      Background

      Antiplatelet agent clopidogrel has been widely used for stroke management for many years, although resistance to clopidogrel may increase the chance of stroke recurrence. CYP2C19 loss-of-function (LoF) polymorphism is assumed to be responsible for the poor metabolism of clopidogrel that ultimately turns to resistance. Previous publications could not provide firm evidence due to highly conflicting and heterogeneous outcomes.

      Aim

      To get clear evidence from an updated meta-analysis on CYP2C19 LoF polymorphism association with stroke risk in clopidogrel treated patients, this study has been performed.

      Methods

      We conducted a meta-analysis with 72 selected studies from authentic databases, including 40,035 coronary artery disease patients treated with clopidogrel.

      Results

      This analysis showed that the worldwide carrier of one or more CYP2C19 LoF alleles had a significantly higher risk of stroke and composite events than the non-LoF carriers (RR=1.78, 95% CI=1.52-2.07, p<0.00001 and RR=1.39, 95% CI=1.26-1.54, p<0.00001, respectively). Besides, subgroup analysis showed that Asian CYP2C19 LoF carriers had a significantly increased risk of stroke (RR=1.91, 95% CI=1.60-2.28, p<0.00001) while the risk of composite events was significantly higher in all ethnic populations (Asian: RR=1.58, 95% CI=1.32-1.89, p<0.00001; Caucasian: RR=1.27, 95% CI=1.08-1.50, p=0.003; Hispanic and others: RR=1.21, 95% CI=1.09-1.34, p=0.0003).

      Conclusion

      Our meta-analysis confirmed that the presence of CYP2C19 LoF alleles increases the risk of stroke and composite events recurrence in the worldwide population, especially in Asians undergoing clopidogrel treatment. Alternative antiplatelet therapy should be investigated thoroughly for the intermediate and poor metabolizers.

      Graphical abstract

      Keywords

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