氯吡格雷与血小板反应

CLEAR PLATELETS: Clopidogrel Loading with Eptifibatide to Arrest the Reactivity of Platelets 1 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 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 in some patients undergoing elective coronary stenting 1. 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. 2 Introduction (contd) Mechanisms of clopidogrel nonresponse/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 600-mg dose1 1. Muller et al. Heart. 2001;85:92. 3 Introduction (contd) A large prospective pharmacodynamic study of clopidogrel 300 mg vs 600 mg is not available The effect of adding eptifibatide to these regimens is unknown ISAR REACT suggested no benefit of adding abciximab to patients loaded with 600 mg clopidogrel1 Patients all pretreated for 2 hours (median 7.4 hours) Risk of bleeding with CABG in patients on clopidogrel therapy2 Low-risk group 1. Kastrati et al. N Engl J Med. 2004;350:232. 2. Hongo et al. J Am Coll Cardiol. 2002;40:231. 4 Objectives of CLEAR PLATELETS Trial Compare platelet reactivity 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 of platelet reactivity to postprocedural myocardial necrosis Analyze the relation of platelet reactivity to postprocedural inflammation Gurbel et al. Circulation. 2005;111:1153. 5 Methods Consecutive patients undergoing elective coronary stenting Exclusion criteria Chest pain 1.5 Platelets 4.0 mg/dL Thienopyridine or GP IIb/IIIa use Elevated cardiac markers CVA 3 ULN) CKMB (1-3 ULN) CKMB (normal) Gurbel et al. Circulation. 2005;111:1153. 17 No MI MI 5 M ADP-Induced Aggregation Mean platelet reactivity (%) P0.01 Relation of Mean Posttreatment Aggregation to Occurrence of MI (n=120) No MI MI 20 M ADP-Induced Aggregation Mean platelet reactivity (%) P0.01 Gurbel et al. Circulation. 2005;111:1153. 18 CKMB ( 1- 3 X ULN ) Patients (%) CKMB ( 3X ULN ) * * *P1 - 3 ULN ) CKMB (3 ULN ) * * Patients (%) Relation of Platelet Reactivity to Myocardial Necrosis 0 10 20 30 Clopidogrel 300 mg Clopidogrel 600 mg Clopidogrel 300 mg + eptifibatide Clopidogrel 600 mg + eptifibatide *P ULN ) Myoglobin ( 2X ULN ) P = 0.08 P = 0.04 P = 0.006 P = 0.09 Gurbel et al. Circulation. 2005;111:1153. EARLY CLINICAL RELEVANCE OF PLATELET REACTIVITY: MYOCARDIAL INFARCTION 21 Troponin-I ( ULN ) Myoglobin (2 ULN ) P=0.08 P=0.04 P=0.006 P=0.09 Patients (%) Early Clinical Relevance of Platelet Reactivity: Myocardial Infarction Clopidogrel 300 mg Clopidogrel 600 mg Clopidogrel 300 mg + eptifibatide Clopidogrel 600 mg + eptifibatide 0 10 20 30 40 50 Gurbel et al. Circulation. 2005;111:1153. 0 0 22 Conclusions Platelet reactivity correlates strongly with the development of periprocedural 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 mg clopidogrel 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 become t