Abstract 4448: Clopidogrel Effect Depends on Body Weight and Abolishes Platelet Leukocyte Interaction in Patients with Coronary Artery Disease Treated by Stenting
Background: Poor response to aspirin and clopidogrel has been associated with an increased risk for thrombotic events after PCI. The optimal dose of clopidogrel is unknown as platelet aggregability (PA) is not routinely measured in clopidogrel treated patients.
Methods and Results: In order to assess potential mechanisms of clopidogrel responsiveness we have performed bedside platelet impedance aggregometry in patients with stable coronary artery disease (group CAD; n=62) and patients who underwent elective PCI (group PCI; n=90) compared to control individuals in whom coronary artery disease was excluded by coronary angiography (group control; n=28). Control patients did not receive antiplatelet therapy, CAD patients were treated with aspirin 100mg/d, and PCI patients with aspirin 100mg/d and clopidogrel 75mg/d. Impedance aggregometry was performed using arachidonic acid [AA] (final conc [fc]: 0.5mM) or ADP (fc: 6.5μM) and the area under the curve (AUC) was quantified to detect the effect of aspirin or clopidogrel, respectively. Indeed, PA was specifically reduced by either drug (AA: [control vs. CAD vs. PCI] 877±300 vs. 183±134 vs. 111±90; ADP: [control vs. PCI] 725±275 vs. 288±174 AUC). We detected a negative correlation between body weight and clopidogrel response (r=0.28; p=0.008), suggesting that clopidogrel may have been underdosed in obese patients. Furthermore, we found a positive correlation between leukocyte counts and PA (r=0.4, p=0.028) confirming that platelets and leucocytes interact functionally. Administration of clopidogrel abolished this interaction as detected by comparison of control individuals with PCI patients but also in intra-individual follow-up tests before and after introduction of clopidogrel.
Conclusion: Impedance aggregometry is useful to assess PA routinely. Dosage of clopidogrel may need to be adjusted in obese patients. PA depends on leukocyte counts confirming that platelet activity is modulated by leukocytes; this interaction is effectively inhibited by clopidogrel.