Observational Study Of CYP2C19 Gene In Patients With Ischemic Stroke Taking Clopidogrel

ObjectivesThis study sought to evaluate the influence of the genetic polymorphisms on platelet reactivity and clinical outcomes in acute ischemic stroke patients taking clopidogrel.MethodsFrom August 2012 to July 2013, patients hospitalized in Changhai Hospital with acute ischemic stroke were randomly assigned to treatment with 75-mg daily maintenance dose of clopidogrel. Genotyping was detected by MassARRAY iPLEX genotyping system (Sequenom Inc, San Diego, CA) and platelet reactivity was measured by the VerifyNow P2Y12 test (Accumetrics Inc., San Diego, California). Seven single nucleotide polymorphisms (SNPs), including CYP2C19*2,*3,*4,*5,*7,*8 and*17, were selected. Clopidogrel low response (CLR) was defined as P2Y12 reaction units (PRU)≥230. The primary endpoint was major adverse cardiac events (MACE), recurrence of stroke, transient ischemic attack, and the composite of vascular death, and the secondary endpoint was bleeding.ResultsOf the 345 patients recruited,275 (79.71%) patients were followed up for one year and 122 (35.36%) patients were categorized as CLR. During the one-year follow-up, a total of 64 (23.61%) cases of clinical events occurred, including 60 the primary endpoints and 4 the secondary endpoints. Among the SNPs selected, only the CYP2C19*2 allele and the CYP2C19*3 allele were associated significantly with PRU (p=0.00007 and p=0.0006, respectively). Similarly, the prevalence of CLR was associated with CYP2C19*2 and CYP2C19*3 (p<0.0001 and p=0.0007, respectively). There were no correlation between CYP2C19 variant alleles and clinical outcomes(p>0.5), but a statistically significant correlation was foun d between the CLR and the primary endpoint in a one-year follow-up (p=0.0009). CLR was an independent risk factor for recurrence of ischemic events (OR 2.149,95%CI 1.183,3.902, p=0.012).ConclusionsCYP2C19*2 and CYP2C19*3 had significant impact on clopidogrel response, but failed to predict prognosis of patients with ischemic stroke. CLR was an independent predictor of ischemic events and the VerifyNow P2Y12 test may be available to guide antiplatelet therapies in stroke patients.