Discussion

Abstract

GP IIb-IIIa RECEPTOR INHIBITORS IN STENTING Dr. Harvey D. White: What data are available about the use of glycoprotein (GP) IIb-IIIa receptor inhibitors in conjunction with coronary artery stenting? Dr. James E. Tcheng: The IMPACT II trial was the first study of a GP IIb-IIIa receptor inhibitor (eptifibatide) that assessed the benefit of this therapy in patients receiving coronary stents. At the time IMPACT II was designed, stenting was not as common as it is today, and only 152 of 3,871 treated patients in the IMPACT II trial (48 in each of the eptifibatide arms and 56 in the placebo group) actually received coronary stents. Nevertheless, patients who received eptifibatide treatment experienced a substantial benefit in terms of a significantly reduced rate (16%) of myocardial infarction (MI) relative to the placebo-treated patients (32%). The incidence of other individual endpoints, such as death, revascularization, and major bleeding events, was comparable between eptifibatide-treated and placebo-treated patients. The major issue here is whether GP IIb-IIIa inhibitor therapy is the best strategy to manage limitations of coronary stenting—primarily endothelial injury that occurs in .30% of cases and can serve as a potent stimulus for coronary thrombosis. Additionally, stents themselves are highly thrombogenic, producing platelet-rich clots 2–14 days after the procedure, which almost invariably leads to MI and death. While a combination of aspirin and ticlopidine has dramatically reduced the rate of thrombotic complications related to stenting, GP IIb-IIIa inhibitors may further reduce platelet aggregation and thrombus formation. Finally, coronary stenting is still associated with a relatively high rate (15–20%) of restenosis, and the potential value of GP IIb-IIIa inhibitors in this setting remains to be clarified. There is clearly a lot we need to learn about the usefulness of GP IIb-IIIa inhibitors as adjuncts to stents, and several trials are addressing some of the important questions. The EPIC, EPILOG, and CAPTURE trials of abciximab in patients at low and high risk for complications after angioplasty included subgroups of patients receiving stents. Combined analysis showed that at 30 days, the composite endpoint of death, MI, or target vessel revascularization was reduced by one third with abciximab. Additional trials are investigating the value of abciximab therapy in this clinical setting. The benefit of GP IIb-IIIa inhibition with eptifibatide in patients receiving stents will be evaluated in the Platelet Aggregation and Receptor Occupancy With Integrilin—A Dynamic Evaluation (PRIDE) trial and other phase III trials. Dr. Robert A. Harrington: The use of stents has dramatically increased over the past few years, both in the United States and globally. Stents provide luminal increase and prevent elastic recoil but are frequently associated with thrombotic complications. GP IIb-IIIa inhibitors effectively block platelet-driven thrombosis and are a useful complement to stents. However, some US interventionalists view GP IIb-IIIa blockers not as a complement but as an alternative to stenting. Dr. White: What is your view on this, Dr. Tcheng? Dr. Tcheng: Personally, I believe that the combination of stenting and GP IIb-IIIa antagonism is the ideal approach. Although stenting addresses the architectural issue (e.g., maintenance of the increased vessel lumen), it also provides a highly thrombogenic substrate, and this is the area where GP IIb-IIIa inhibitors are going to be useful. Considering the importance of platelets in restenosis, I also think that GP IIb-IIIa inhibition, as well as blockade of platelet deposition and activation, will show some long-term benefit. Wider acceptance of GP IIb-IIIa inhibitors in conjunction with stents will depend on the outcome of ongoing clinical trials, which I just described. But, again, my view is that GP IIb-IIIa blockers are a perfect complement to stents.