The emerging role of platelet glycoprotein IIb/IIIa inhibitors in managing high-risk patients with non-ST segment elevation acute coronary syndromes

Background: Current practice guidelines recommend administering a platelet glycoprotein llb/llla inhibitor, in conjunction with aspirin and heparin, for patients with non-ST segment elevation (NSTE) acute coronary syndromes (ACS) for whom an early invasive management strategy is planned. However, optimal timing of glycoprotein llb/llla inhibitor administration -'upstream' in the coronary care unit or 'downstream' when the patient goes to the catheterization laboratory - has not been established. Scope: This paper evaluates recent trial results that help to better define the role of platelet glycoprotein llb/llla inhibitors for treating high-risk patients with NSTE ACS who are scheduled for percutaneous coronary intervention (PCI). The Medline database was searched in February 2007 to retrieve relevant articles. Additional articles were obtained from the reference lists of retrieved articles, as well as from recent scientific meetings and company websites. Findings: Results of the ISAR-REACT 2 trial indicate that administration of abciximab provides significant benefit for high-risk patients with NSTE ACS undergoing PCI; clopidogrel alone is not enough. In preliminary results of the ACUITY trial, glycoprotein llb/llla inhibitor administration produced an incremental increase in bleeding events but a reduction in ischemic events; there was a trend to better outcomes with upstream administration, even short-term. Moreover, in the cohort of patients who underwent PCI, the composite ischemic endpoint was significantly lower with routine upstream glycoprotein llb/llla inhibitor. Finally, results of the EVEREST pilot study, a mechanistic study evaluating epicardial and tissue level perfusion and cardiac troponin I release, significantly favored upstream administration of tirofiban over downstream glycoprotein llb/llla inhibitor for high-risk patients with NSTE ACS undergoing PCI. Moreover, high bolus dose tirofiban or abciximab administered just before PCI produced similar effects on angiographic outcome and cardiac troponin I release. Conclusions: Recent and emerging evidence is clarifying the role of glycoprotein llb/llla inhibitors in treating high-risk patients with NSTE ACS and indicates that these agents are of greatest benefit when given early.