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Emergency department (ED) physicians are critical in the accurate diagnosis, efficient management, and treatment of patients with ST-segment elevation myocardial infarction. The initial reperfusion strategy involves the choice between mechanical reperfusion using primary percutaneous coronary intervention and pharmacologic treatment with fibrinolytics. The benefits of these approaches are time dependent, and practices vary according to institutional resources and local guidelines. Nevertheless, the need for early intervention and the use of certain therapies are well recognized. Therefore, ED physicians must be aware of all treatment options available, including the use of adjunctive therapies. Initial treatment should include β-blockers, aspirin (or clopidogrel if aspirin is contraindicated), nitroglycerin, and analgesia, regardless of reperfusion strategy. Clopidogrel is now approved as an adjunctive therapy for patients undergoing fibrinolysis as their reperfusion therapy. Both unfractionated heparin and low-molecular-weight heparin are feasible adjunctives in patients with ST-segment elevation myocardial infarction undergoing reperfusion therapy. In addition, multiple new antithrombin agents are being investigated. The choice adjunctive treatments should be based on specific patient populations and on the initial reperfusion strategy.