How to optimise clopidogrel therapy? Reducing the low-response incidence by aggregometry-guided therapy modification

Summary

The inhibitory platelet effect of clopidogrel is insufficient in approximately 5 to 30% of patients. These low responders (LR) face a significantly higher risk of cardiovascular complications. The therapeutic management of LR is still undefined. In the present study, we evaluate a novel therapeutic algorithm to reduce the incidence of clopidogrel resistance. One hundred sixty-one patients on 100 mg ofAspirin co-medication underwent elective coronary stenting and were given an initial dosage of 600 mg clopidogrel, followed by 75 mg clopidogrel daily. 48 h later, the platelet responsiveness was tested with ADP (5–20 μM) stimulation by impedance aggregometry (Chronolog 590). A significant rise in impedance (> 5 Ω after 6 minutes, aggregation index > 65%) was defined as LR. In this subgroup, platelets were stimulated with the selective P2Y₁₂-ADP receptor antagonist 2-MeS AMP. One hundred twenty-three patients were clopidogrel-responders (76.4%) and 38 patients were LR (23.6%). A defect of the ADP-receptor P2Y₁₂ was found in three out of 38 LR (7.9%). Inhibition of platelet aggregation indicating clopidogrel-responsiveness was achieved with either a clopidogrel high-dose regimen (22/38, 57.9%); a repeat loading dose, doubling the maintenance dose) or with an alternative therapy with ticlopidine (8/38 (21.1%); 250 mg twice daily).Thus the incidence of LR was reduced from 23.6% to 5.0%. Our aggregometer–guided therapeutic algorithm reduced the relative percentage of clopidogrel LR by 78.9%.This approach could prove to be helpful in achieving a further decrease in the incidence of clopidogrel resistance.

Keywords

Aggregation - clopidogrel - low-responder - resistance - ticlopidine

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