Key result
CYP2C19 poor metabolizers on clopidogrel exhibit ~82% high residual platelet reactivity vs extensive metabolizers.
Why the study?
Does CYP2C19 phenotype status correlate with platelet function test results in cardiovascular disease patients receiving clopidogrel?
Observational (n=83)
Does CYP2C19 phenotype status correlate with platelet function test results in cardiovascular disease patients receiving clopidogrel?
Absolute Event Rate: 82.4% vs 11.8%
p-value: p=<0.001
CYP2C19 loss-of-function genotypes are highly prevalent in Korean patients and significantly correlate with reduced clopidogrel efficacy as measured by multiple platelet function tests, including the PFA-200.
PFA-200 detects CYP2C19-related variability in clopidogrel response; hypothesis-generating for genotype-guided therapy.
BACKGROUND: An association has been reported between CYP2C19 polymorphism and the altered antiplatelet activity of clopidogrel. We investigated this association using the newly introduced platelet function analyzer (PFA)-200 (INNOVANCE PFA-200 System; Siemens Healthcare, Germany) P2Y test. METHODS: Polymorphisms of CYP2C19*2, *3, *17 and the degree of inhibition of platelet function were determined in 83 patients. Three different platelet function tests were used to evaluate the degree of platelet inhibition and to check the association with genotype. RESULTS: The post-procedure PFA-200 values of extensive metabolizers (EM) patients (285.3±38.8) were higher than those of intermediate metabolizers (IM) and poor metabolizers (PM) patients (227.7±98.3 and 133.7±99.2, respectively; P=0.024). Light transmittance aggregometry (LTA) and the VerifyNow system showed that the post-procedure values for EM patients were lower than those of IM and PM patients (LTA: 24.4±15.7, 34.1±17.6, and 42.2±16.9, respectively, P<0.001; VerifyNow: 133.2±60.5, 171.5±42.6, and 218.7±59.3, respectively, P<0.001). The high residual platelet reactivity (HPR) rates were significantly different among the EM, IM, and PM groups using PFA-200 (PM:IM:EM=82.4:40.6:11.8, P<0.001). CONCLUSIONS: Approximately, 59.0% of Korean patients with cardiovascular disease receiving clopidogrel had CYP2C19 loss-of-function genotypes classified as IM or PM, and the frequency was similar to the data from Asian people. The PFA-200, LTA, and VerifyNow platelet function tests revealed evidence of a significant association between the efficacy of clopidogrel and CYP2C19 genotypes.
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Li et al. (2015) conducted an observational in Cardiovascular disease (n=83). CYP2C19 loss-of-function genotypes (Poor or Intermediate Metabolizers) vs. Extensive metabolizers (EM) was evaluated on High residual platelet reactivity (HPR) rates using PFA-200 (p=<0.001). CYP2C19 poor and intermediate metabolizers receiving clopidogrel had significantly higher rates of high residual platelet reactivity than extensive metabolizers (82.4% and 40.6% vs 11.8%; P<0.001).
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