Genetic Polymorphisms and Clopidogrel Efficacy for Acute Ischemic Stroke or Transient Ischemic Attack: A Systematic Review and Meta-analysis
Background—The association of genetic polymorphisms and clopidogrel efficacy in patients with ischemic stroke or transient ischemic attack (TIA) remains controversial. We performed a systematic review and meta-analysis to assess the association between genetic polymorphisms, especially CYP2C19 genotype, and clopidogrel efficacy for ischemic stroke or TIA.
Methods—We conducted a comprehensive search of the PubMed and EMBASE from their inceptions to June 24, 2016. Studies that reported clopidogrel-treated patients with stroke or TIA and with information on genetic polymorphisms were included. The endpoints were stroke, composite vascular events and any bleeding.
Results—Among 15 studies of 4,762 patients with stroke or TIA treated with clopidogrel, carriers of CYP2C19 loss-of-function alleles (*2, *3 and/or *8) were at increased risk of stroke compared with non-carriers (12.0% vs. 5.8%; risk ratio (RR): 1.92, 95% confidence interval [CI]: 1.57-2.35; p<0.001). Composite vascular events were also more frequent in carriers of CYP2C19 loss-of-function alleles compared with non-carriers (13.7% vs. 9.4%; RR: 1.51, 95%CI: 1.10-2.06; p=0.01), while bleeding rates were similar (2.4% vs. 3.1%; RR: 0.89, 95%CI: 0.58-1.35; p=0.59). There was no evidence of statistical heterogeneity among the included studies for stroke, but there was for composite vascular events. Genetic variants other than CYP2C19were not associated with clinical outcomes except significant associations of PON1, P2Y12 and COX-1 with outcomes were observed in one study.
Conclusions—Carriers of CYP2C19 loss-of-function alleles are at greater risk of stroke and composite vascular events compared with non-carriers among patients with ischemic stroke or TIA treated with clopidogrel.
- Received August 8, 2016.
- Revision received September 21, 2016.
- Accepted October 11, 2016.