Evaluation of oral Xemilofiban in Controlling Thrombotic Events - EXCITE Xemilofiban

Description:

Xemilofiban vs. placebo for thrombotic events in acute coronary syndromes

Hypothesis:

To evaluate efficacy and safety of oral glycoprotein IIb/IIIa inhibition following acute coronary syndromes.

Study Design

Study Design:

Patients Screened: Not given
Patients Enrolled: 7232
Mean Patient Age: 59
Female: 22

Patient Populations:

Age 21-80
Stable or unstable angina
Recent myocardial infarction >24 hours since hospitalization
Target lesion >70% stenosis
Successful PTCA or stent placement.

Primary Endpoints:

Event-free survival (death, nonfatal myocardial infarction, and urgent revascularization) at 30 days and 6 months.

Drug/Procedures Used:

Xemilofiban 10mg, xemilofiban 20mg, or placebo 3 times a day for 2 weeks and then 2 times daily for 2 weeks

Concomitant Medications:

All patients received aspirin and ticlopidine if they received a stent.

Principal Findings:

A total of 2414 patients were randomized to placebo, 2400 to xemilofiban 10 mg, and 2418 to xemilofiban 20 mg. Eighteen percent of patients had diabetes. There were equal numbers of patients with unstable angina (45%) and stable angina (43%), with only 15% of subjects having myocardial infarction. Seventy percent received stents.

The combined event rate of death and myocardial infarction at 30 days and 6 months was not statistically significant for either dose of xemilofiban. The 30-day combined event rate was 6.5% for placebo, 6.5% for xemilofiban 10mg, and 5.6% for xemilofiban 20mg (P value= 0.161 between placebo and xemilofiban 20mg). The 6-month combined event rate was 9.1% for placebo, 9.3% for xemilofiban 10mg, and 8.2% for xemilofiban 20mg (P value= 0.238 between placebo and xemilofiban 20mg). The combined endpoint at 1 day was significantly different between the placebo and xemilofiban 20mg groups. However, this difference disappeared after several days. There was also no difference between the groups for the combined endpoint of death, myocardial infarction, and urgent revascularization.

Interpretation:

Intravenous glycoprotein IIbIIIa inhibitors have been studied extensively in trials such as EPIC, EPILOG, EPISTENT, and PURSUIT, and have been shown to be beneficial in patients undergoing PTCA or stent placement. Xemilofiban is an oral nonpeptide glycoprotein IIbIIIa inhibitor which provides 90% platelet inhibition for 8 to 10 hours after a single dose. Unlike the intravenous glycoprotein IIbIIIa inhibitors, EXCITE did not show a benefit in combined cardiovascular endpoints. Other studies of oral GP IIbIIIa inhibitors are in progress.

References:

1. Presented at the ACC 48th Scientific Sessions, New Orleans, LA, 1999

Clinical Topics: Acute Coronary Syndromes, Invasive Cardiovascular Angiography and Intervention, Stable Ischemic Heart Disease, Interventions and ACS, Chronic Angina

Keywords: Myocardial Infarction, Acute Coronary Syndrome, Platelet Aggregation Inhibitors, Angina, Stable, Blood Platelets, Constriction, Pathologic, Benzamidines, Diabetes Mellitus, Stents, Platelet Glycoprotein GPIIb-IIIa Complex


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