Clopidogrel effect on platelet reactivity in patients with stent thrombosis: Results of the CREST study

OBJECTIVES: We investigated whether patients who suffered subacute stent thrombosis (SAT) have higher post-treatment reactivity than those who do not encounter stent thrombosis. BACKGROUND: High post-treatment platelet reactivity has been reported after coronary stenting after clopidogrel therapy and may be an important factor in the occurrence of SAT. METHODS: We identified patients with SAT treated at two tertiary care centers over a 1.5-year period. Light transmittance aggregation induced by adenosine diphosphate (ADP) and arachidonic acid, total and activated glycoprotein (GP) IIb/IIIa after stimulation with ADP, and vasodilator-stimulated phosphoprotein phosphorylation levels to measure P2Y₁₂ receptor inhibition were determined (n = 20) and compared with an age-matched group of patients without SAT (n = 100). High post-treatment platelet reactivity was defined as >75th percentile ADP-induced aggregation in the group without SAT. RESULTS: The SAT patients had higher mean platelet reactivity than those without SAT by all measurements (p < 0.05): 49 ± 4% versus 33 ± 2% for 5 μmol/l ADP-induced aggregation and 65 ± 3% versus 51 ± 2% for 20 μmol/l ADP-induced aggregation (p < 0.001), 69 ± 5% versus 46 ± 9% for P2Y₁₂ reactivity ratio (p = 0.03), and 138 ± 19 mean fluorescence intensity (MFI) versus 42 ± 4 MFI for stimulated GP IIb/IIIa expression (p < 0.001). Of patients with SAT, 60% had high platelet reactivity. CONCLUSIONS: High post-treatment platelet reactivity and incomplete P2Y₁₂ receptor inhibition are risk factors for SAT. Measures to uniformly determine platelet reactivity after coronary stenting and treatment strategies to improve P2Y ₁₂ receptor inhibition in patients with high post-treatment platelet reactivity should be further investigated.