Randomized, Placebo-Controlled Trial of Platelet Glycoprotein IIb/IIIa Blockade With Primary Angioplasty for Acute Myocardial Infarction

Abstract

on behalf of the ReoPro and Primary PTCA Organization and Randomized Trial (RAPPORT) Investigators* Background-The benefit of catheter-based reperfusion for acute myocardial infarction (MI) is limited by a 5% to 15% incidence of in-hospital major ischemic events, usually caused by infarct artery reocclusion, and a 20% to 40% need for repeat percutaneous or surgical revascularization. Platelets play a key role in the process of early infarct artery reocclusion, but inhibition of aggregation via the glycoprotein IIb/IIIa receptor has not been prospectively evaluated in the setting of acute MI. Methods and Results-Patients with acute MI of Ͻ12 hours' duration were randomized, on a double-blind basis, to placebo or abciximab if they were deemed candidates for primary PTCA. The primary efficacy end point was death, reinfarction, or any (urgent or elective) target vessel revascularization (TVR) at 6 months by intention-to-treat (ITT) analysis. Other key prespecified end points were early (7 and 30 days) death, reinfarction, or urgent TVR. The baseline clinical and angiographic variables of the 483 (242 placebo and 241 abciximab) patients were balanced. There was no difference in the incidence of the primary 6-month end point (ITT analysis) in the 2 groups (28.1% and 28.2%, Pϭ0.97, of the placebo and abciximab patients, respectively). However, abciximab significantly reduced the incidence of death, reinfarction, or urgent TVR at all time points assessed (9.9% versus 3.3%, Pϭ0.003, at 7 days; 11.2% versus 5.8%, Pϭ0.03, at 30 days; and 17.8% versus 11.6%, Pϭ0.05, at 6 months). Analysis by actual treatment with PTCA and study drug demonstrated a considerable effect of abciximab with respect to death or reinfarction: 4.7% versus 1.4%, Pϭ0.047, at 7 days; 5.8% versus 3.2%, Pϭ0.20, at 30 days; and 12.0% versus 6.9%, Pϭ0.07, at 6 months. The need for unplanned, "bail-out" stenting was reduced by 42% in the abciximab group (20.4% versus 11.9%, Pϭ0.008). Major bleeding occurred significantly more frequently in the abciximab group (16.6% versus 9.5%, Pϭ0.02), mostly at the arterial access site. There was no intracranial hemorrhage in either group. Conclusions-Aggressive platelet inhibition with abciximab during primary PTCA for acute MI yielded a substantial reduction in the acute (30-day) phase for death, reinfarction, and urgent target vessel revascularization. However, the bleeding rates were excessive, and the 6-month primary end point, which included elective revascularization, was not favorably affected. (Circulation. 1998;98:734-741.)

Restoration of Normal Coronary Flow With Tirofiban by Intracoronary Administration for No-reflow Phenomenon After Stent Deployment

“…For example, intracoronary administration of abciximab, 13) a monoclonal antibody directed against the glycoprotein IIb/IIIa receptor, and tirofiban, 14) a synthetic nonpeptide small-molecule platelet glycoprotein IIb/ IIIa receptor inhibitor, were shown to be able to dissolve an intracoronary thrombus, although both are not thrombolytic agents. Glycoprotein IIb/IIIa antagonists were also reported to reduce major ischemic events in the PAPPORT 15) and CADILLAC 16) trials. However, they do not improve the percentage of patients achieving TIMI grade 3 flow after direct percutaneuos coronary intervention.…”

“…5) Why did tirofiban restore the flow in our patient but not in previous studies? [15][16][17] The most striking difference is our route of intracoronary administration rather than the intravenous adminstration used in previous studies. With venous administration, a long time is needed before the drug reaches the lesion, and thus, the drug could be metabolized, bound to protein, or diluted by the body pool.…”

Efficacy and Safety of Unfractionated Heparin Plus Glycoprotein IIb/IIIa Inhibitors During Revascularization for an Acute Coronary Syndrome: A Meta‐Analysis of Randomized Trials Performed With Stents and Thienopyridines

“…These agents have been the subject of many randomized trials, including early studies that did not use coronary stents and thienopyridines. 3,4 Recent meta-analysis and a randomized trial of GPIs during PCI for ACS have drawn divergent conclusions from an earlier report about the clinical utility of these agents. 5 -7 Our aim, therefore, is to reappraise the benefits and risks of GPIs in ACS patients, specifically those treated with stents and thienopyridines.…”

Pharmacoinvasive Therapy

“…[43][44][45][46] (2) GP IIb/IIIa inhibitors are helpful for reducing recurrent MI and urgent target vessel revascularization; the evidence for their ability to contribute to a reduction in mortality rates is less clear. [47][48][49][50][51] Abciximab is the best-studied of the GP IIb/IIIa inhibitors; only limited angiographic data are available on the small molecule inhibitors. 52 It appears helpful to administer abciximab before arrival in the catheterization laboratory so that platelet inhibition has been initiated before coronary instrumentation.…”