Immediate Pharmacology in the Current Era of Reperfusion Therapy

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US Cardiology, 2006;3(2):1-4

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Effective translation of reperfusion therapy to mortality reductions in ST-segment elevation myocardial infarction (STEMI) remains both time-critical in its implementation and dependent on optimal antithrombotic therapy. Innumerable clinical studies have explored several antithrombin and antiplatelet therapies in the immediate management of STEMI. With the wide array of the therapies now available, the choice of agents initiated before reperfusion in the context of both catheter-based and pharmacologic reperfusion needs to be rational and evidence-based. Furthermore, with an apparent ceiling in mortality benefit observed in clinical trials, benefits in terms of reduced recurrent myocardial infarction (MI) and reduced bleeding events become increasingly important considerations.

Before considering the evidence supporting the various pharmacotherapies, it is useful to review the goals of reperfusion therapy for STEMI. Emergent restoration of epicardial, and therefore myocardial, blood flow is aimed at preservation of cardiac muscle integrity and electrical stability, hopefully leading to reductions in death. In achieving this goal, both catheter-based and pharmacologic reperfusion have recognised limitations. These include: an apparent ceiling in efficacy in terms of mortality reduction; attenuated benefit due to re-infarction; bleeding complications including catastrophic events such as intracerebral hemorrhage; and often, inability to achieve timely access for all patients, particularly when considering primary percutaneous coronary intervention (PCI). Hence, innovations in adjunctive pharmacology in this context need to address at least one of these limitations, and ideally all of them.

Beginning in the era of fibrinolysis, adjunctive antiplatelet therapy with aspirin has been established as a cornerstone of effective reperfusion.This evidence has led to the exploration of more robust approaches to antiplatelet therapy as an adjunct to both catheter-based and pharmacologic reperfusion. Initial studies with abciximab, an intravenous (IV) glycoprotein IIb/IIIa inhibitor, demonstrate robust reductions in the composite of death and MI by 30 days and six months, with modest increases in bleeding events among patients undergoing PCI.1 While the data with abciximab has been mixed, especially within trials of relatively low-risk STEMI patients, meta-analysis of the entire clinical trial experience of 27,115 patients suggests that a 1% absolute reduction in mortality is achieved compared with placebo (abciximab: 2.4% versus 3.4%, p=0.047) by 30 days in the context of catheter-based reperfusion with benefits sustained in late follow-up.2,3 Appropriately controlled comparative data with the small molecule intravenous glycoprotein IIb/IIIa inhibitors eptifibatide and tirofiban are currently lacking, though improvements in perfusion are reported.4

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