Timeliness of treatment is more important than choice of reperfusion therapy

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Great strides have been made in reperfusion therapy in recent years. Adjunctive therapy with clopidogrel (Plavix) and enoxaparin (Lovenox) has been shown to improve outcomes with fibrinolytic therapy. Bivalirudin (Angiomax) and stents have improved primary PCI’s performance. Reducing bleeding complications has become a clinical priority, with increasing emphasis on adjusting some drug doses according to renal function and using the radial artery for cardiac catheterization.

The American College of Cardiology initiative, “Door-to-Balloon (D2B): An Alliance for Quality,” focused much attention on organizing in-hospital systems of care for primary PCI, thus increasing the national rate of achieving a door-to-balloon time within 90 minutes from 50% to over 75% in patients who presented to hospitals with PCI capability.6

The American Heart Association has launched “Mission: Lifeline,” a national campaign to organize prehospital systems of care with their program,7 working within communities to address their unique needs, resources, and barriers to implementing systems of care for ST-elevation MI. The key aspect of this effort is to help geographic regions develop local solutions, an explicit recognition that there is no one-size-fits-all solution. Early triage by emergency medical services, rapid diagnosis with prehospital electrocardiography, destination and interhospital transfer protocols, and prehospital activation of the cardiac catheterization laboratory can greatly streamline emergency care and decrease treatment delays for primary PCI.


So what about hospitals without PCI capability that cannot routinely transfer patients to a hospital with PCI capability within 90 minutes?

Lessons learned from the experiences with immediate PCI, rescue PCI, and facilitated PCI have evolved into the “pharmacoinvasive strategy.” Patients with ST-elevation MI are treated as rapidly as possible with a bolus of a fibrinolytic drug, eg, tenecteplase (TNKase) or reteplase (Retavase), and are also given aspirin, clopidogrel, and enoxaparin. Then, they are rapidly transferred to a PCI-capable hospital so that emergency PCI can be performed if reperfusion is not clinically apparent or if the patient develops pulmonary edema or cardiogenic shock. If the clinical signs suggest that reperfusion has been achieved (relief of chest pain, rapid resolution of ST-segment elevation, bursts of accelerated idioventricular rhythm), coronary angiography (and PCI, if indicated) can be performed within 3 to 24 hours of fibrinolytic therapy. This time frame allows the initial fibrinolytic effect to dissipate, while the antiplatelet and anticoagulant drugs achieve therapeutic levels.

Today, the goal is to treat every patient with the best reperfusion strategy available, given the limitations in resources and the geographic location of some centers, and to maximize the possibility of sustained patency of the infarct-related artery by implanting a stent, even if it takes several hours and transfer to another hospital to perform PCI.8 The pharmacoinvasive strategy of rapid administration of fibrinolytic therapy followed by PCI within 24 hours would be practical in most hospitals without PCI capability where treatment delays prohibit performance of primary PCI within 90 minutes of first medical contact.9


As proof of concept, the Strategic Reperfusion Early After Myocardial Infarction (STREAM) trial is enrolling 2,000 patients with ST-elevation MI presenting within 3 hours of symptom onset if primary PCI is not feasible within 60 minutes of first medical contact.10 Patients will be randomized to either of the following:

  • Receive prehospital therapy with tenecteplase, aspirin, clopidogrel, and enoxaparin and undergo cardiac catheterization in 6 to 24 hours (or rescue PCI if reperfusion fails within 90 minutes of fibrinolysis)
  • Undergo primary PCI performed according to local guidelines.

The primary measure of efficacy will be the composite rate of death, cardiogenic shock, heart failure, and reinfarction at 30 days. Measures of safety include the rates of ischemic stroke, intracranial hemorrhage, and major nonintracranial bleeding.

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