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Patients with high-risk characteristics admitted for non-ST elevation acute coronary syndromes benefit from an early invasive treatment, and in this case glycoprotein (GP) IIb/IIIa inhibitors appear effective in improving prognosis. There is however an ongoing debate on which of the currently available agents is the best in patients who are candidates for percutaneous coronary interventions. The dispute revolves on the optimal level of inhibition of platelet function and on whether the benefit is retained in the presence of pretreatment with thienopyridines. Especially the additional value of GP IIb/IIIa inhibition on top of an aggressive antithrombotic therapy (including aspirin, heparins, and clopidogrel) requires further clarification. Here we propose an algorithm for the practical use of available GPIIb/IIIa antagonists in relation with the patient’s clinical presentation and concomitant use of other drugs and devices.