There is clear data demonstrating the benefits of the antiplatelets aspirin and thienopyridenes  in the management of patients with<unk>  elevation MI treated with fibrinolytic administration. The benefits of clopidogrel vs placebo in patients undergoing primary angioplasty have not been established in randomized trials, although non-randomized registry data is consistent with a benefit of clopidogrel in this setting.  The benefit of aspirin plus thienopyridine therapy versus aspirin monotherapy alone could be difficult to establish in randomized trials given that the majority of<unk> EMI patients are treated with a<unk> ent which in turn obviates chronic thienopyridine treatment.  Despite the required chronic thienopyridine therapy following<unk> ent placement, the slower onset of action of oral thienopyridines relative to that of parenteral antiplatelet agents such as<unk> <unk>  inhibitors raises important questions as to the acute / early benefits of<unk> <unk>  inhibitors versus thienopyridines. Furthermore, the optimal timing of thienopyridine therapy in primary PCI is not well established. In so far a few patients undergo coronary artery bypass grafting (CABG) surgery urgently in the setting of<unk> EMI, the need to define the anatomy prior to theinopyridine administration may not be as compelling as it is in the setting of<unk> able angina, unstable angina and non-ST elevation MI.
Current guidelines recommend pre-loading with 300 to 600 mg of clopidogrel in the primary PCI setting. Again, it should be emphasized that this is not based upon randomized trial data enrolling<unk> EMI patients undergoing primary PCI, but rather from data originating from non-randomized subgroup analyses and registries. One registry demonstrated that pre-loading with clopidogrel in the setting of<unk> EMI was associated with a 2.2 fold improvement in normal TIMI myocardial perfusion grade 3 (O.R. 1.2-3.9, p=0.01) was well as a reduced risk of recurrent MI (0% vs 3.2%, respectively, p= 0.04) .  In a subgroup of 2707 patients managed with primary PCI in the Acute Coronary Syndromes (ACOS) registry, 1 year mortality was significantly reduced among patients treated with aspirin plus clopidogrel versus aspirin alone (OR 0.38, 95% CI 0.23-0.62]. It should be noted that this data is limited by the fact that neither the loading dose nor timing of clopidogrel were reported . It should also be realized that in registries, clopidogrel administration is often a surrogate or a marker of the use of a<unk> ent, and it is not clear whether the benefit was mediated by the<unk> ent or by the clopidogrel.  Finally, Gibson et al in a substudy from CLARITY have demonstrated that non-emergent PCI after fibrinolytic therapy was associated with improved mortality among patients randomized to clopidogrel (OR 0.34, 95% CI 0.13-0.92, P = .034) but not placebo (OR 1.41, 95% CI 0.63-3.19, P = .40, interaction P = .028).<unk> <unk>  inhibitors are a third class of antiplatelet agents that have, in contrast to aspirin and clopidogrel, been<unk> udied extensively in the setting of<unk> EMI treated with primary PCI. Meta analyses of randomized trial data do support a clinical event reduction (including a<unk> rong trend toward a mortality reduction) among<unk> EMI patients treated with GPIIb/IIIa inhibitors . In contrast to primary PCI, there is no clinical benefit of GPIIb/IIIa<unk>  when added to the administration of a full dose of a fibrinolytic agent when co-administered at the time of presentation with<unk> EMI.  This combination is clearly associated with increased bleeding, particularly in the elderly .  The benefit of<unk> <unk>  administration in the cardiac catheterization laboratory several hours after fibrinolytic administration is supported by non-randomized observational data .
There are several clinical questions regarding GP<unk><unk>  in the setting of<unk> EMI that have not been definitively resolved in randomized trials:
ST elevation myocardial infarction glycoprotein IIbIIIa inhibition
Unstable angina / non ST elevation myocardial infarction GPIIb/IIIa inhibitor
Unstable angina / non ST elevation myocardial infarction inhibitors of RAS
Unstable angina / non ST elevation myocardial infarction factor Xa inhibitors therapy
Unstable angina / non ST elevation myocardial infarction direct thrombin inhibitors therapy
Chronic stable angina treatment clopidogrel
ST elevation myocardial infarction management of patients who were not reperfused
Unstable angina / non ST elevation myocardial infarction calcium channel blockers