Abstrakt:
Background: Prognostic values of genotyping and
phenotyping for assessment of clopidogrel responsiveness have
been shown in independent studies. Objectives: To compare
different assays for prediction of events during long-term
follow-up. Methods: In this prospective cohort study polymorphisms
of CYP2C19*2 and CYP2C19*17 alleles, vasodilator-
stimulated phosphoprotein phosphorylation (VASP)
assay, multiple electrode aggregometry (MEA), cone and
platelet analyser (CPA) and platelet function analyser (PFA-
100) were performed in 416 patients undergoing percutaneous
coronary intervention. The rates of events were recorded during
a 12-month follow-up. Results: Platelet aggregation by MEA
predicted stent thrombosis (2.4%) better (c-index = 0.90;
P < 0.001; sensitivity = 90%; specificity = 83%) than the
VASP assay, CPA or PFA-100 (c-index < 0.70; P > 0.05;
sensitivity < 70%; specificity < 70% for all) or even the
CYP2C19*2 polymorphism (c-index < 0.56; P > 0.05; sensitivity
= 30%; specificity = 71%). Survival analysis indicated
that patients classified as poor responders by MEA had a
substantially higher risk of developing stent thrombosis or
MACE than clopidogrel responders (12.5% vs. 0.3%,
P < 0.001, and 18.5% vs. 11.3%, P = 0.022, respectively),
whereas poor metabolizers (CYP2C19*1/*2 or *2/*2 carriers)
were not at increased risks (stent thrombosis, 2.7% vs. 2.5%,
P > 0.05; MACE, 13.5% vs. 12.1%, P = 0.556). The incidence
of major bleedings (2.6%) was numerically higher in
patients with an enhanced vs. poor response to clopidogrel
assessed by MEA (4% vs. 0%) or in ultra-metabolizers vs.
regular metabolizers (CYP2C19*17/*17 vs. CYP2C19*1/*1;
9.5% vs. 2%). The classification tree analysis demonstrated that
acute coronary syndrome at hospitalization and diabetes
mellitus were the best discriminators for clopidogrel responder
status. Conclusions: Phenotyping of platelet response to clopidogrel
was a better predictor of stent thrombosis than
genotyping.