Present and potential future paradigms for the treatment of ST-segment elevation acute myocardial infarction

Derek P. Chew, David J. Moliterno, Howard C. Herrmann

Research output: Contribution to journalReview article

7 Citations (Scopus)

Abstract

There are four principal reasons for using GP IIb/IIIa inhibition in the treatment of AMI: to improve early reperfusion; to stabilize patients before, during, and after PCI; to improve cardiac function; and to confer an overall survival advantage. The advent of platelet GP IIb/IIIa inhibition in the management of AMI has created the opportunity to bridge the treatment gap between fibrinolytic monotherapy and PCI, both of which are effective but have practical and clinical limitations. Fibrinolysis is more widely available and does not require in-hospital catheterization laboratory access, whereas primary PCI offers the potential for increased rates of reperfusion and reduced rates of mortality and ICH. Platelet GP IIb/IIIa inhibition offers the clinician a variety of therapeutic choices for the treatment of AMI; it can be used in combination pharmacotherapy with reduced-dose fibrinolysis and offers several advantages prior to PCI (some dethrombosis effects and reduced peri-procedural incidence of death or MI) with and without stents. Of the three available GP IIb/IIIa inhibitors, abciximab is the most studied agent in PCI, in direct and rescue PTCA, with stenting, and in combination with reduced-dose fibrinolytics. Compared with placebo or conventional therapy, abciximab has been shown to produce significant reductions in death, reinfarction and urgent TVR, as well as higher TIMI 3 flow rates, more rapid resolution of ST-segment elevation, improved 30-day and 6-month mortality, reduced infarct size and improved LV function. Nevertheless, several issues remain to be clarified. First, while heparin (or alternative forms of antithrombin therapy) is an essential component of strategies to establish microvascular perfusion and achieve mortality reduction, it is also clearly linked to bleeding risk. Attempts to determine the optimal dosing of UFH within the context of combined fibrinolysis and GP IIb/IIIa inhibition have yielded conflicting results, perhaps reflecting the use of different fibrinolytic agents and the ability of the GP IIb/IIIa inhibitor to suppress thrombin generation. Second, the clinical importance of the following is uncertain: the differences among GP IIb/IIIa antagonists with respect to potency; effects on the other adhesion molecules such as MAC-I and the vitronectin receptor; and efficacy in protecting the microvasculature. Third, the timing of microembolization (either before or after complete occlusion of the epicardial vessel) is uncertain. Potentially, pharmacologic reperfusion with combined attenuated fibrinolysis and GP IIb/IIIa inhibition may actually increase the degree of distal embolization observed. Furthermore, the benefits of this combined approach may be dependent on the extent and duration of microvascular injury (beyond a point of no return). Whether a novel pharmacologic approach to reperfusion may narrow or broaden the window of opportunity in which maximal mortality benefit is achieved remains to be demonstrated. Despite these issues, the GUSTO-V trial is a key outcomes study defining the benefits of combined fibrinolytic and GP IIb/IIIa inhibition for coronary reperfusion. Moreover, while further refinement of this strategy may be required, such a combination may form a logical basis for merging pharmacological and catheter-based (facilitated PCI) reperfusion. However such a strategy will require prospective evaluation. Table 4 represents the many studies supporting the use of GP IIb/IIIa inhibitors in ST-segment elevation AMI.

Original languageEnglish
JournalJournal of Invasive Cardiology
Volume14
Issue numberSUPPL. A
Publication statusPublished - 23 Feb 2002
Externally publishedYes

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging
  • Cardiology and Cardiovascular Medicine

Cite this