氯吡格雷与血小板反应ppt课件

1、Clopidogrel Loading with Eptifibatide to Arrest the Reactivity of Platelets Introduction We have previously reported a significant incidence of clopidogrel resistance in patients post-elective coronary stenting treated with a standard 300-mg loading dose1 (31% at 24 hours) Patients with clopidogrel

2、resistance/high post-stent platelet reactivity may be at greatest risk of SAT and ischemic events2-4 Relation of peri-procedural platelet reactivity to myocardial necrosis has never been prospectively studied These data suggest that 300 mg clopidogrel/75 mg qd does not provide sufficient inhibition

3、in some patients undergoing elective coronary stenting1. Gurbel et al. Circulation. 2003;107:2908.2. Muller et al. Thromb Haemost. 2003;89:783.3. Barragan et al. Catheter Cardiovasc Interv. 2003;59:295.4. Matetzky et al. Circulation. 2004;109:3171.Introduction (contd) Mechanisms of clopidogrel nonre

4、sponse/resistance are incompletely defined? Due to inadequate levels of active metabolite? Overcome by a higher dose Study of 30 pts (n=10 for ticlodipine, n=10 for clopidogrel 300 mg, n=10 for clopidogrel 600 mg) suggested better inhibition with 600 mg at 4 hours but no difference at 24 hours with

5、600-mg dose11. Muller et al. Heart. 2001;85:92.Introduction (contd) A large prospective pharmacodynamic study of clopidogrel 300 mg vs 600 mg is not available The effect of adding eptifibatide to these regimensis unknown ISAR REACT suggested no benefit of adding abciximab to patients loaded with 600

6、 mg clopidogrel1 Patients all pretreated for 2 hours (median 7.4 hours) Risk of bleeding with CABG in patients on clopidogrel therapy2 Low-risk group1. Kastrati et al. N Engl J Med. 2004;350:232.2. Hongo et al. J Am Coll Cardiol. 2002;40:231.Objectives of CLEAR PLATELETS Trial Compare platelet react

7、ivity following 4 treatments in low- to moderate-risk patients undergoing elective stenting Without pretreatment (CRUSADE) coronary anatomy unknown prior to procedure DOSING 600 mg Clopidogrel 600 mg Clopidogrel + eptifibatide 300 mg Clopidogrel 300 mg Clopidogrel + eptifibatide Analyze the relation

8、 of platelet reactivity to postprocedural myocardial necrosis Analyze the relation of platelet reactivity to postprocedural inflammationGurbel et al. Circulation. 2005;111:1153.Methods Consecutive patients undergoing elective coronary stenting Exclusion criteria Chest pain 24 h AMI 1.5 Platelets 4.0

9、 mg/dL Thienopyridine or GP IIb/IIIa use Elevated cardiac markers CVA 3 mo Visible thrombus Hct 3 ULN)CKMB(1-3 ULN)CKMB(normal)Gurbel et al. Circulation. 2005;111:1153.No MIMI5 M ADP-Induced Aggregation Mean platelet reactivity (%)P0.01Relation of Mean Posttreatment Aggregation to Occurrence of MI (

10、n=120)No MIMI20 M ADP-Induced Aggregation Mean platelet reactivity (%)P0.01Gurbel et al. Circulation. 2005;111:1153.CKMB ( 1- 3 X ULN )Patients (%)CKMB ( 3X ULN )0102030300 mg C600 mg C300 mg C + E600 mg C + E*P1 - 3 ULN )CKMB (3 ULN )*Patients (%)Relation of Platelet Reactivity to Myocardial Necros

11、is 0102030Clopidogrel 300 mg Clopidogrel 600 mgClopidogrel 300 mg + eptifibatide Clopidogrel 600 mg + eptifibatide*P ULN )Myoglobin ( 2X ULN )P = 0.08P = 0.04P = 0.006P = 0.09Gurbel et al. Circulation. 2005;111:1153.Troponin-I( ULN )Myoglobin (2 ULN )P=0.08P=0.04P=0.006P=0.09Patients (%)Early Clinic

12、al Relevance of Platelet Reactivity: Myocardial InfarctionClopidogrel 300 mg Clopidogrel 600 mgClopidogrel 300 mg + eptifibatide Clopidogrel 600 mg + eptifibatide01020304050Gurbel et al. Circulation. 2005;111:1153.00Conclusions Platelet reactivity correlates strongly with the development of periproc

13、edural myocardial necrosis in elective stenting When clopidogrel pretreatment is not possible or when the duration of pretreatment is inadequate, a strategy of eptifibatide administration should be considered since it is associated with superior platelet inhibition and lower myocardial necrosis than either 300 mg or 600 mgclopidogrel alone In the absence of eptifibatide, a strategy of clopidogrel 600 mg clearly provides superior platelet inhibition compared with the standard 300-mg dose A 600-mg loading dose should becom