Preeminence Toward a New Frontier in Myocardial Reperfusion Therapy : Emerging Platelet

For more than a decade, intravenous thrombolytic therapy has been validated for the reduction of mortality in evolving MI. Reperfusion therapy is the standard of care for patients with acute MI who present early (within 12 hours of symptom onset) and have significant ECG STsegment elevation. However, the limitations of the therapy are especially impressive. First, even the most potent established thrombolytic therapy does not achieve restoration of early and complete coronary blood flow in '50% of patients. This '50% failure rate is particularly important because the relationship of successful reperfusion and survival is quite strong, such that the death rate among patients who fail to achieve early reperfusion is at least twofold to threefold higher. Second, thrombolytic therapy induces a relatively high rate of intracerebral hemorrhage. Although the incidence is '1 in 150 to 200 treated patients, the event is usually catastrophic, resulting in fatality or a disabling stroke. Of note, the ability to predict intracerebral bleeding is quite limited; save for the commonly present demographic factors of the aged and hypertension, little is known about who is predisposed or why this dreaded complication occurs. In the recently completed third Global Utilization of Strategies to Open Occluded Arteries (GUSTO-III) trial, which assessed reteplase and alteplase, the incidence of hemorrhagic stroke was increased compared with previous trials. The overall rate of 0.9%, or '1 in 100 patients, reflects, in part, the enrollment of more elderly and hypertensive patients and emphasizes the significance of the problem in contemporary trials and likely clinical practice. Third, thrombolytic therapy has been shown to be inferior to catheter-based reperfusion for achieving infarct vessel patency and reducing the incidence of death or nonfatal MI. Furthermore, the incidence of hemorrhagic stroke is reduced with primary balloon angioplasty. The superiority of mechanical over pharmacological reperfusion points out the limited efficacy of the latter but at the same time sets a higher standard that can be achieved with respect to improved clinical outcomes. Because mechanical reperfusion is available only in specialized centers and is logistically cumbersome, a primary objective is to achieve parity between a pharmacological strategy, which is eminently more practical and universally available, and catheter-based reperfusion, if at all possible. At present, for patient triage, a critical decision has to be made to choose between these two alternatives. The reason this has evolved is that the clinical trials that tested immediate balloon angioplasty after thrombolytic therapy all showed a higher rate of major complications compared with thrombolytic therapy alone or balloon angioplasty performed without antecedent thrombolysis. These trials were performed in the mid to late 1980s and have had a remarkable impact in dichotomizing the two alternative reperfusion strategies. The explanation for the phenomenon of the untoward effects of angioplasty after thrombolysis is probably the prothrombotic tendencies of fibrinolytic agents, as will be fully discussed. Virtually all of these limitations of pharmacological reperfusion therapy may be abrogated, at least in part, with newly available potent antiplatelet inhibitors. In this article, their potential to affect a radical change in our approach to myocardial reperfusion will be reviewed.