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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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
Country-Specific Mortality and Growth Failure in Infancy and Yound Children and Association With Material Stature
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