The Evaluation To The Efficacy And Safety Of Tirofiban In Acute Coronary Syndrome Patients With Clopidogrel Resistance During Percutaneous Coronary Intervention

Objective: The aim of this study was to assess the efficacy and safety of the tirofiban in acute coronary syndrome patients with clopidogrel resistance undergoing selective percutaneous coronary intervention (PCI).Methods: From April 2007 to December 2008, 90 patients ( 58 male and 32 female, average age was 64.7±4.4 years old ) who had been diagnosed as acute coronary syndrome with clopidogrel resistance were enrolled in to this study. Clopidogrel resistance was defined as absolute reduction of platelet aggregation rate < 10%. Patients with bleeding diathesis, thrombocytopenia, recent stroke, hypersensitiveness of clopidogrel and tirofiban were excluded. These 90 cases were randomly divided into two groups, that is, the high maintenance clopidogrel group (n=50, 35 males, 15 females, 150 mg clopidogrel per day) and the tirofiban group (n=40, 30 males, 10 females during percutaneous coronary intervention operation the tirofiban was pumpped continuely ). All the patients underwent PCI after 7-10day's medical treatment . we collected detailed clinical information including: age, gender, risk factors, pathological changes of coronary artery .We measured the platelet aggregation rate of the two groups at the time of baseline, 5 hours after loading dose , the markers of platelet activation------ both PAC-1 and CD62P were measured before and 0.5h,6h,12h after PCI.All patients received selective PCI. All patients received 300 mg oral clopidogrel loading dose, aspirin and Low Molecular Heparin injection in both groups. We used SAS 6.12 statistics software to analyse all data. The variables were presented as the means and the SD. Differences between two groups means were assessed with the t test. TheΧ2 analysis or the Fisher exact test were used to test differences between proportions. Statistical significance was indicated by P < 0.05.RESULT:1 There is no significant difference in age, gender, risk factors and pathological changes of coronary artery between the high maintenance clopidogrel group and tirofiban group. There is no significant difference in the platelet aggregation rate after 300mg clopidogrel.2 The expression rate of platelet activation markers CD62p and PAC-1 in normal control group is 3.56±1.41 and 3.11±1.50, the expression rate of CD62P and PAC-1 in the clopidogrel group is 11.91±3.04 and 11.68±3.13, the expression rate CD62P and PAC-1 in the tirofiban group is 11.97±3.06 and 11.72±3.55. The expression rate of CD62P and PAC-1 in the high maintenance clopidogrel group and the tirofiban group is higher than the normal control group, the difference is significant. But it is no difference between clopidogrel group and the tirofiban group.3 After the medical treatment the expression rate of CD62P and PAC-1 in the tirofiban group is higher than the clopidogrel group(P<0.05).4 At the time of 0.5h after PCI the expression rate of CD62P and PAC-1 in the high maintenance clopidogrel group is 8.07±2.09 and 8.48±2.47,tirofiban group is 5.73±3.07 and 4.41±1.55, 0.5h after PCI The expression rate of CD62P and PAC-1in the clopidogrel group is higher than before PCI (p < 0.05). Untill 12h after PCI the expression rate of CD62P and PAC-1 is dropped dwon to the before PCI. In the tirofiban group the expression rate of CD62P and PAC-1at 0.5h after PCI is lower than before PCI, untill 12h after PCI the expression rate of CD62P and PAC-1declined gradually.There were less MACE cases in the high maintenance clopidogrel group than the tirofiban group in hospital (6.0% vs 2.5% p < 0.05). There was no significant difference in hemorrhage events between two groups.Conclusion:1 The expression rate of CD62P and PAC- 1 in the patients with acute coronary syndrome is higher than the normal control group, it is show that platelet was activatied in patients with ACS. 2 150 mg/d clopidogrel can inhibit the activation of platelet but 75 mg/d clopidogrel can't in patients of ACS with clopidogrel resistance.3 150 mg/d clopidogrel can't inhibit the activation of platelet thanks to PCI itseft ,but tirofiban is GP IIb/IIIa antagonists,it can blockade the combination of fibrinogen and platelet GP IIb/IIIa receptor-----PAC-1, can strongly inhibit platelet activation and improve platelet resistent to clopidogrel.4 Tirofiban can decreases the MACE cases of patient with clopidogrel resistent during PCI but do not increase the hemorrhage events.