BACKGROUND: Platelet reactivity (PR) is enhanced in patients presenting with acute myocardial infarction (AMI) and optimal inhibition of platelet aggregation is paramount in reducing ischemic cardiovascular events in this population. Carriers of the cytochrome P-450 (CYP) 2C19 mutant alleles have significantly lower levels of the active metabolite of clopidogrel and diminished platelet inhibition. Because Asian population shows a higher prevalence of CYP 2C19 polymorphism, it may affect clinical outcomes in AMI patients. However, the degree of platelet inhibition by standard dose of clopidogrel in Asian patients with AMI is not determined.
METHODS: The study prospectively enrolled AMI patients undergoing emergent percutaneous coronary intervention (PCI) (n = 268). Immediately after hospitalization, all patients received a 600-mg loading of clopidogrel followed by a maintenance-dose of 75 mg/day. Pre-discharge PR was assessed with conventional aggregometry and the VerifyNow assay, at least 3 days after PCI. High post-clopidogrel PR (HPPR) was defined as 5 uM ADP-induced PR ≥ 50% or P2Y12 reaction unit (PRU) ≥ 240, based on previous studies.
RESULTS: Antiplatelet response to clopidogrel showed a normal, bell-shaped distribution. PRs with 5 and 20 uM ADP stimuli were 44.3 ± 15.7% and 57.1 ± 14.9%, respectively, with PRU value of 245 ± 82. The cut-off of highest quartiles for 5uM ADP-induced PR and PRU were 56% and 304, respectively. Patients showed a higher prevalence of HPPR (40.3% with 5 uM ADP-induced PR ≥ 50% and 55.6% with PRU ≥ 240). The 5 uM ADP-induced PR was significantly higher in female (50.8 ± 13.1% vs. 42.3 ± 15.9%, P = 0.013) and age ≥ 60 year (47.5 ± 14.2% vs. 39.0 ± 16.4%, P < 0.001).
CONCLUSIONS: Standard maintenance-dose of clopidogrel (75mg) can’t achieve adequate platelet inhibition during early phase of AMI in Asian Patients. For Asian patients with AMI undergoing PCI, introduction of intensified antiplatelet therapy will be important to reduce the risk of ischemic events.
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