Abstract 3217: Prasugrel 60/10 mg Compared with Clopidogrel 600/75 mg Results in Fewer Poor Responders Using Definitions of Platelet Reactivity Associated with Clinical Outcomes
Purpose: At least four definitions in the clinical literature of insufficient platelet inhibition by clopidogrel have been linked to clinical endpoints:
Change in maximal platelet aggregation (ΔMPA) <10% associated with post-PCI myonecrosis;
MPA >50% associated with postprocedural ischemic events 1 y after PCI. C) Residual platelet aggregation (RPA) at 6 min >14% linked to 30 d MACE post-PCI; D) Platelet reactivity index (PRI) with VASP>50% linked to subacute stent thrombosis.
A 600 mg clopidogrel loading dose (LD) has been advocated to decrease clopidogrel response variability.
Methods: After a run-in on 75 mg aspirin, 110 patients were randomly assigned to double blind treatment with either clopidogrel (n=55) 600 mg LD followed by 75 mg o.d. (once daily) maintenance dose (MD) for 28 days or prasugrel (n=55) 60 mg LD followed by 10 mg o.d. MD for 28 days. The individual response to treatment was evaluated by turbidimetric light transmission aggregometry (LTA) (definition A–C) and VASP (definition D) at pre-dose 1, 2, 4, 24h post-LD and repeated pre-dose at days 14 and 29. Pharmacodynamic (PD) poor response was defined as above (definitions A–D).
Results: There was no significant difference in clinical characteristics or MPA level at baseline. The number of PD poor responders was greater in the clopidogrel group for all tested definitions at all time-points.
Conclusion: There were significantly fewer PD poor responders with a prasugrel 60 mg LD compared to a 600 mg LD of clopidogrel, regardless of the definition used. The four definitions of “clopidogrel resistance” tested have all been associated with an increased number of atherothrombotic cardiovascular events. Prasugrel treatment may reduce the risk of thrombotic complications by limiting the number of patients with insufficient ADP receptor inhibition.