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Understanding the pathology of acute coronary syndromes has led to significant improvements in patient outcome. Platelet adhesion to the arterial wall, especially under high shear forces, such as are present in stenotic arteries, is facilitated through multiple high-affinity interactions between platelet membrane receptors and ligands within the exposed subendothelium, most notably collagen and von Willebrand factor. Platelet activation, initiated by the collagen exposed by plaque disruption and locally-generated soluble platelet agonists (primarily thrombin, ADP, and thromboxane A2), results in release of growth factors and adhesion molecules and most importantly the activation of the coagulation pathway. Activation of adjacent platelets occurs, with conformational changes in the platelet GP IIb IIIa receptor. Platelet aggregation, mediated primarily by interaction between the activated platelet GP IIb IIIa receptor and its ligands, fibrinogen and vWF, results in the formation of the platelet-rich thrombus. It is the formation of this platelet-rich clot and its extent at sites of coronary stenosis, plaque erosion, or a recent plaque rupture that determine the clinical consequences in acute coronary syndromes by altering vessel patency.
Antiplatelet therapy has therefore become central to the management of non-ST elevation MI, although the complex nature of the clot and the presence of multiple constituents suggest potential additional benefit from direct antithrombins such as bivalirudin1 and low molecular weight heparin,2 but interestingly, and despite the presence of “red thrombus”, not from thrombolytic therapy. The impact of any treatment on outcome will also be influenced by other factors such as the amount of myocardial territory at risk, amount of myocardium already jeopardised, the balance between presenting ischaemia versus previous infarction, heterogeneity amongst the population in terms of risk factors (diabetes, age), as well as the confounder of having three antiplatelet agents with different, specific and potentially interactive efficacies being used against a background of …