The role of glycoprotein IIb/IIIa inhibitors in primary percutaneous coronary intervention for ST elevation myocardial infarction.

The administration of glycoprotein IIb/IIIa inhibitors is considered to provide additional benefit to mechanical reperfusion in the treatment of patients with ST elevation myocardial infarction and is included as a class-IIa recommendation in the Guidelines for Percutaneous Coronary Intervention of the European Society of Cardiology. Glycoprotein IIb/IIIa inhibitors block the surface receptor, which is a member of the integrin superfamily of membrane-bound adhesion molecules. Binding to the major adhesive proteins, fibrinogen and von Willebrand, occurs due to a conformational change of the glycoprotein IIb/IIIa receptor. This final step in platelet aggregation is blocked by the glycoprotein IIb/IIIa inhibitors. Other effects of the glycoprotein IIb/IIIa receptor are interference with thrombus formation, including induction of platelet disaggregation, and reduced clot retraction. Inhibitors developed and used in routine clinical practice include abciximab, the Fab fragment of the chimeric monoclonal antibody, 7E3, and synthetic intravenous administered competitive integrin blocking agents, such as tirofiban and eptifibatide. Effects on clinical outcome of adding glycoprotein IIb/IIIa to primary percutaneous coronary intervention (PCI) in patients with ST elevation myocardial infarction have been evaluated in a randomized fashion primarily for abciximab, whereas the clinical effects of tirofiban and epitifibatide are less well investigated. A pooled analysis of 3949 patients from five larger and three smaller randomized controlled trials found that the addition of abciximab to primary PCI reduced 30-day mortality from 3.4 to 2.4% (P 1⁄4 0.047) and 6–12-month mortality from 6.2 to 4.4% (P 1⁄4 0.01). With a risk reduction of 1% at 30 days, the estimated number needed to treat to prevent one death was 100, and the risk reduction of 1.8% at 6–12-month follow-up corresponds to an estimated number needed to treat 56 patients. Abciximab was also associated with a significant reduction in 30-day re-infarction rate from 1.9 to 1.0% (P 1⁄4 0.03), corresponding to a number needed to treat 111 patients to prevent one re-infarction. With regard to safety, this pooled analysis reconfirms that abciximab was not associated with a higher incidence of intracranial bleeding. To assess the equivalency of the different glycoprotein IIb/IIIa inhibitors, a systematic review of all 12 randomized placebo-controlled trials of glycoprotein IIb/IIIa inhibitor facilitation in patients undergoing urgent or elective PCI has been published recently. Using three complementary methods (Bayesian analysis, Bayesian analysis incorporating prior information, and indirect comparisons via hierarchical Bayesian meta-analysis), Brophy and Joseph showed a reasonable probability of equal effect. The clinically obtained arguments in favour of equivalency of the three inhibitors are in line with similar levels of inhibition of platelet aggregation and with a similar reduction in the platelet–monocyte interaction that were observed when the inhibitors were compared given in standard dose. In a trial of 112 patients with ST elevation myocardial infarction undergoing PCI, Ernst et al. investigated the effect of abciximab, tirofiban, high-dose tirofiban, or no glycoprotein IIb/IIIa inhibitors on the extent of platelet aggregation. The direct comparison of standard dose abciximab with standard dose tirofiban yielded non-significant results. However, it was observed that high-dose tirofiban induced a mean periprocedural platelet aggregation inhibition of 84% compared with 46 and 59% in patients treated with standard dose abciximab and tirofiban, respectively. The benefits of the use of glycoprotein IIb/IIIa inhibitors in patients with ST elevation myocardial infarction treated with PCI have raised the question whether early treatment with these inhibitors, with the aim to improve initial patency before intervention, may further improve outcome. The Abciximab before Direct angioplasty and stenting in Myocardial Infarction Regarding Acute and Long-term follow-up (ADMIRAL) study was the first randomized controlled trial in which a subset of patients were treated with abciximab in the ambulance or in the