Coupling Drug and Catheter Therapy for Myocardial Infarction
Authors: A. Michael Lincoff
Journal: JAMA (2004)

NOTWITHSTANDING EFFICACY DEMONSTRATED IN randomized trials, reperfusion strategies for acute myocardial infarction (MI) remain subject to considerable limitations. A plateau of mortality reduction seemingly has been reached with fibrinolytic therapy, a lack of progress that may relate to the apparent “ceiling” of coronary patency achieved with these drugs, reocclusion, or impaired microvascular tissue level reperfusion. Moreover, the catastrophic complication of intracranial hemorrhage continues to occur in up to 1% of patients receiving fibrinolytic agents. Mechanical approaches to revascularization with balloon angioplasty or coronary stenting overcome some limitations of pharmacologic reperfusion, as randomized trials comparing fibrinolysis with primary percutaneous coronary intervention (PCI) in general have shown the latter to be associated with lower rates of death or reinfarction and markedly diminished hemorrhagic complications. Difficulties also exist with primary PCI, however, including limited availability and delays in mobilizing catheterization laboratory teams. These logistical barriers may substantially prolong the time to reperfusion by mechanical means over that which can be achieved by simply administering a thrombolytic agent, an important limitation given the inverse relationship between clinical benefit and time-to-therapy. Recent randomized trials have confirmed the superiority of PCI over thrombolysis even among patients who initially present tohospitalswithoutangioplasty facilitiesandrequire transfer to interventional centers. Nevertheless, it seems logical that theefficacyofacute therapy forMImightbebetter ifdelays in coronary reperfusion could be minimized. “Facilitated PCI” is an approach to merging the best known aspects of pharmacologic and mechanical approaches to myocardial reperfusion, whereby fibrinolytic or antithrombotic agents are administered immediately upon a patient’s presentation with acute infarction to “bridge the gap” until primary PCI can be performed. The goal is to achieve at least some degree of coronary recanalization, thus limiting myocardial necrosis, during the delay required to transport patients to the catheterization laboratory and perform definitive revascularization. Thrombolytic agents are an obvious choice for such pharmacologic pretreatment, given their ability to restore coronary patency, but concerns regarding bleeding in conjunction with PCI have prompted investigation of alternative regimens. Substantial randomized trial data have established periprocedural administration of platelet glycoprotein (Gp) IIb/ IIIa inhibitors as an effective means of diminishing periprocedural ischemic complications and perhaps reducing longterm mortality in the setting of elective or urgent PCI. Pilot angiographic studies have also suggested that these agents have thrombus “disaggregatory” properties, with coronary patency rates after administration being similar to those achieved with streptokinase in the setting of acute MI. Bleeding complications with these agents have generally been modest, and intracranial hemorrhage rates do not appear to be increased. These findings provide rationale for extending the use of Gp IIb/IIIa inhibitors into the medical management phase prior to PCI among patients with acute MI. Improved and more stable coronary patency has been observed with regimens combining half-dose fibrinolytics with Gp IIb/IIIa inhibitors. Although mortality has not been reduced by combination therapy compared with conventional thrombolytic monotherapy in large-scale randomized trials of “stand-alone” pharmacologic reperfusion, combination regimens may be well-suited for a strategy of facilitated PCI. In this issue of THE JOURNAL, Kastrati and colleagues report the results of the first randomized comparison of 2 different pharmacologic approaches to facilitated PCI for acute MI: abciximab (a Gp IIb/IIIa inhibitor) alone or the combination of abciximab plus half-dose reteplase. One hundred eighty-six (74%) of 253 patients presented to institutions without interventional facilities, thus requiring hospital transfer for PCI. As expected, patients who received combination therapy had higher coronary patency rates than those treated with abciximab alone (40% vs 18%, respectively) at the time of initial angiography at a median 2 hours after study drug administration. However, this angiographic advan-