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Pharmacological Facilitation of Primary Percutaneous Coronary Intervention for Acute Myocardial Infarction:  Is the Slope of the Curve the Shape of the Future?

Bernard J. Gersh, MB, ChB, FRCP; Gregg W. Stone, MD; Harvey D. White, DSc; David R. Holmes, MD
JAMA. 2005;293(8):979-986. doi:10.1001/jama.293.8.979.
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Current options for reperfusion therapy in patients admitted to a community hospital without cardiac catheterization facilities include administration of fibrinolytic drugs followed by observation, with referral to angiography driven by symptoms and signs of ischemia; transfer to a tertiary care center for primary percutaneous coronary intervention (PCI); or a strategy of facilitated PCI in which administration of fibrinolytics and platelet glycoprotein IIb/IIIa inhibitors (alone or in combination) is followed by transfer for immediate angiography and PCI if appropriate. We systematically analyzed multiple randomized and nonrandomized trials to review the pathophysiology of reperfusion therapy in acute myocardial infarction to derive insights about the likelihood of success of a strategy of facilitated PCI compared with transfer only or fibrinolysis only. The basis for the recommendations made herein is a hypothetical curve relating the duration of symptoms before reperfusion to reduction in mortality and extent of myocardial salvage. During the first 2 to 3 hours after symptom onset, a striking benefit of reperfusion is present; within this period, time to treatment is critical. Subsequently, a mortality benefit is still present but of decreasing magnitude over time. In this situation, the priority is to open the artery, and time to treatment is less critical. Results of facilitated PCI may depend largely on timing of presentation. If presentation is late after symptom onset (ie, on the “flat” part of the curve), there will be little mortality benefit from earlier patency and patients will be subject to the bleeding risks of fibrinolytic drugs. In contrast, among patients presenting very early (60-90 minutes after symptom onset), outcomes with fibrinolytic therapy alone are excellent, and it will be difficult for any other strategy to result in a significant improvement. But in patients presenting 2 to 3 hours after onset of symptoms, a strategy of facilitated PCI may move patients from the plateau to the descending limb of the curve, with a substantial improvement in myocardial salvage and mortality. Two large ongoing trials may provide definitive answers to these issues.

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Figure. Hypothetical Construct of the Relationship Among the Duration of Symptoms of Acute MI Before Reperfusion Therapy, Mortality Reduction, and Extent of Myocardial Salvage
Graphic Jump Location

Mortality reduction as a benefit of reperfusion therapy is greatest in the first 2 to 3 hours after the onset of symptoms of acute myocardial infarction (MI), most likely a consequence of myocardial salvage. The exact duration of this critical early period may be modified by several factors, including the presence of functioning collateral coronary arteries, ischemic preconditioning, myocardial oxygen demands, and duration of sustained ischemia. After this early period, the magnitude of the mortality benefit is much reduced, and as the mortality reduction curve flattens, time to reperfusion therapy is less critical. If a treatment strategy, such as facilitated percutaneous coronary intervention (PCI), is able to move patients back up the curve, a benefit would be expected. The magnitude of the benefit will depend on how far up the curve the patient can be shifted. The benefit of a shift from points A or B to point C would be substantial, but the benefit of a shift from point A to point B would be small. A treatment strategy that delays therapy during the early critical period, such as patient transfer for PCI, would be harmful (shift from point D to point C or point B). Between 6 and 12 hours after the onset of symptoms, opening the infarct-related artery is the primary goal of reperfusion therapy, and primary PCI is preferred over fibrinolytic therapy. The possible contribution to mortality reduction of opening the infarct-related artery, independed of myocardial salvage, is not shown. Modified from Gersh and Anderson.6

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