Antithrombotic therapy to support primary PCI.

The goals of the initial management of ST-segment elevation myocardial infarction include swift restoration of flow within the occluded coronary artery, prevention of early reinfarction, and avoidance of complications of reperfusion therapy.1,2 The selection of the reperfusion strategy, either the preferred percutaneous coronary intervention (PCI) or fibrinolysis, is usually driven by institutional access to primary PCI. Thus, the decision that clinicians most commonly grapple with at the time of the patient’s presentation is the selection of adjunctive anticoagulant and antiplatelet therapy. In this issue of the Journal, Stone and colleagues report on a large, randomized trial that tested an anticoagulant agent in primary PCI.3 When performed rapidly by an experienced team, primary PCI restores flow in the culprit artery in more than 95% of patients and, as compared with fibrinolysis, reduces the risk of reinfarction by more than 50%, but with a higher risk of extracranial bleeding.4 Thus, the goals of antithrombotic therapy for primary PCI differ from those for fibrinolysis, which fails to restore coronary flow or culminates in early reocclusion in approximately 20% of patients.5 Antithrombotic therapy in primary PCI is focused on minimizing the thrombotic complications of mechanical intervention. Only modest absolute reductions in early spontaneous reinfarction are possible because the absolute risk is 3% or less.4 Although antithrombotic therapy facilitates improved flow before angiography, the effect appears to be small if the pretreatment is brief. Current guidelines for ancillary antithrombotic therapy recommend that patients who are undergoing primary PCI receive aspirin and a loading dose of clopidogrel, generally 600 mg, before or at the time of PCI.1,2,6 On the basis of expert consensus, unfractionated heparin is recommended in patients undergoing primary PCI (class I [treatment should be administered], according to the American College of Cardiology/American Heart Association guidelines).1 The glycoprotein IIb/IIIa-receptor inhibitor abciximab, which is administered intravenously, has been evaluated in seven randomized, placebo-controlled trials involving a total of approximately 4000 patients undergoing primary PCI, with mixed results.7 In aggregate, these trials suggest that abciximab treatment is associated with a reduction in reinfarction and in mortality at 30 days (odds ratio for reinfarction, 0.56; 95% confidence interval [CI], 0.33 to 0.94; and odds ratio for mortality, 0.68; 95% CI, 0.47 to 0.99).7 Few data are available for the glycoprotein IIb/IIIa inhibitors eptifibatide and tirofiban in primary PCI. Taking into consideration observations from PCI in unstable angina and non–ST-elevation myocardial infarction, abciximab is recommended as reasonable (class IIa [it is reasonable to administer treatment]) and eptifibatide or tirofiban is considered to be possibly useful (class IIb [treatment may be considered]) to support primary PCI.1 In clinical practice in the United States, administration of unfractionated heparin and a glycoprotein IIb/IIIa antagonist is the most common ancillary regimen for primary PCI.8 A large, randomized trial of the pentasaccharide factor Xa inhibitor fondaparinux in patients with ST-segment elevation myocardial infarction, including 3789 patients who were undergoing primary PCI, revealed a possible hazard related to catheter thrombosis.9 Therefore, fondaparinux is not recommended as the sole anticoagulant for primary PCI.2,6 Evaluation of low-molecular-weight heparins in patients undergoing primary PCI has not been sufficient to allow recommendation of the use of these agents for this indication. The direct thrombin inhibitor bivalirudin is a short-acting anticoagulant that, when administered for a short interval during PCI, has been found to reduce bleeding as compared with heparin plus a glycoprotein IIb/IIIa inhibitor.10 The trial of bivalirudin in primary PCI reported by Stone et al. addressed an important and untested hypothesis. Strengths of the trial include a large sample, a well-defined population that is relevant to clinical practice, and a comparison of bivalirudin with a treatment that is representative of contemporary practice. The primary result, that bivalirudin alone reduced a composite end point of major bleeding and major cardiovascular events by 24% at 30 days owing to a 40% reduction in the primary bleeding end point, is compelling with respect to the potential for bivalirudin as antithrombotic therapy in this setting.