Risk Factors Of Clopidogrel Resistance And Impact Of Different Proton Pump Inhibitors On The Antiplatelet Activity Of Clopidogrel

ObjectiveTo analyze the clopidogrel resistance morbidity rate, clinical feature and risk factors in patients with cardiovascular and cerebral disease, and evaluate the impact of different proton pump inhibitors on the antiplatelet activity of clopidogrel.Methods1,128 patients with stable cardiac and cerebral vascular diseases, diabetes mellitus, taking clopidogrel 75mg/d≥30 days, and then their blood samples were collected for determination of optical platelet aggregation index using adenosine diphosphate (ADP). CR was defined as a state in which aggregation≥50% with ADP. The difference in clinical characteristics among the groups and independent risk factors associated with CR were analyzed.2,A total of 60 hospitalized patients undergoing percutaneous coronary intervention were randomly assigned to receive Omeprazole group 40mg/d(20 patients) or Pantoprazole group 40mg/d(20 patients) or control group. All patients also received standard clopidogrel therapy. Continuouing 30 days treatments, the percentage clotting inhibition was measured by the use of thrombelastogram and the maximal platelet aggregation rate(MPAR) was measured by turbidity method at the first day before admission and 15 or 30 days after treatment.3,A total of 406 hospitalized patients undergoing percutaneous coronary intervention(PCI) were randomly assigned to receive Omeprazole 40mg/d (146 patients) or Pantoprazole 40mg/d (140 patients)and control group(120 patients).All patients also received standard clopidogrel and asprin ant platelet therapy. The end point were major adverse cardiac and cerebral events(MACCE) within 30 days, which included cardiac death, on-fatal myocardial infarction(MI),urgent target vessel revascularization(UTVR),stroke or sub-acute instant thrombosis(SAT) and hemorrhagic events.Results1,Of 128 patients,16.4% were CR.CR was correlated with diabetes complication, increase of Hs-CRP level and increase of LDL-Ch. CR has no relation to proton pump inhibitors and Statins. Logistic regression analysis showed that diabetes mellitus and high levels of hs-CRP were independent risk factors of CR.2,The baseline clinical characteristics,angiography and PCI result were compared between the three groups. At the first day before admission and 15 or 30 days after treatment, no significant difference were shown in the percentage clotting inhibition measured by thrombelastogram and the maximal platelet aggregation rate(MPAR) measured by turbidity method between the three groups. Though the levels measured at 15 and 30 days declined slightly compared with the baseline data (P<0.05), no significant difference was found between levels measured at 15 and 30 days.3,The rates of MACCE and cardiac death, MI,UTVR,SAT,stroke were 8.45%,0.70%,2.11%,3.52%,1.41%,0.70% respectively in Omeprazole group, and were 7.97%,0.72%,2.90%,2.90%,0.72%,0.72% respectively in Pantoprazole group.The control group was 8.33%,0.83%,1.66%,3.33%,1.66%,0.83% respectively.No significant difference were shown between the three groups. The rates of hemorrhagic event in the Omeprazole group,Pantoprazole group and control group were 6.33%,6.52%,10.83% respectively. Significant decrease were shown in Omeprazole or Pantoprazole group compared with control group (P<0.01), but no significant difference were shown between the Omeprazole and Pantoprazole group.Conclusions1,The incidence rate of CR was 16.4%. Diabetes mellitus and high levels of hs-CRP were independent risk factors of CR. CR has no relation to proton pump inhibitors and Statins.2,No significant impact of different proton pump inhibitors on the antiplatelet activity of clopidogrel has been found in patients undergoing coronary stent implantation and short-time combined administration is safe...