Influence Of Antiplatelet Effect Of Clopidogel When Co-Administered With Atorvastatin And Lansoprazole At The Same Time

Background:Clopidogrel is a irreversible P2Y12 receptor antagonist metabolised by hepatic cytochrome P450 (CYP450) and need convert into activated metabolite to inhibit platelet aggregation. The most important converting enzyme contains CYP3A4, CYP2C19. Lipid-soluble statins are metabolised by CYP3A4,and most PPIs are metabolised by CYP2C19.A number of researches reported that using clopidogel combine with lipid-soluble statins or PPIs may inhibit the activation of clopidogrel and decrease the anti-platelet efficacy. But some other studies did not find this drug-interaction. But to date, there is no study focused on the efficacy of clopidogrel when the three drugs are used at the same time.Objective:We sought to assess the impact of efficacy of clopidogrel and clinical adverse events when clopidogrel is coadministered with atorvastatin and lansoprazole at the same time.Methods and Results:104 consecutive patients diagnosed with NSTE-ACS underwent PCI with drug-eluting stent implantation are included in the present study. All patients are treated with 300 mg loading dose of clopidogrel and 300mg loading dose of asprin within 6-12 hours before PCI followed by asprin 100 mg daily and clopidogrel 75 mg daily maintenance therapy after operation. Rosuvastatin 10mg daily is used for anti-inflammatory therapy after stent implantation.The basic platelet function is assessed on the sixth day after PCI (DO). After the first platelet function assessment, patients are randomised to receive different treatments: asprin+clopidogel+atorvastatin+lansoprazole (A group)、 asprin+clopidogel+atorvastatin (B group)、 asprin+clopidogel+lansoprazole (C group)、 asprin+clopidogel+rosuvastatin (D group).Then retest the platelet function on D15 and D3. All the patients are treated as the study prescription for 6months continuously and follow bleeding and ischemic events happened in this period. RESULTS:No statistical difference was found between groups of patients with general clinical data. Stratified according to time, there is no significant difference among 4 groups (P> 0.05).Stratified according to group, the level of ADP-IPA%、 MAADP、 P-selection、 sCD40L show difference in group D (P< 0.05).It can be interpreted by the patients’ response to clopidogrel enhanced over time. And the the apparent differences was found in 15 days after treatment with clopidogel. In the following 6months, no significant bleeding events happened, a total of 12 patients with ischemic events, the results have no difference between groups (P> 0.05)。Conclusion:Patients diagnosed with NSTE-ACS underwent PCI with drug-eluting stent implantation administered clopidogrel, atorvastatin and lansoprazole at the same time did not decrease the anti-platelet efficacy of clopidogrel and did not increase the adverse events.