Early versus delayed, provisional eptifibatide in acute coronary syndromes.

Abstract

BACKGROUND:

Glycoprotein IIb/IIIa inhibitors are indicated in patients with acute coronary syndromes who are undergoing an invasive procedure. The optimal timing of the initiation of such therapy is unknown.

METHODS:

We compared a strategy of early, routine administration of eptifibatide with delayed, provisional administration in 9492 patients who had acute coronary syndromes without ST-segment elevation and who were assigned to an invasive strategy. Patients were randomly assigned to receive either early eptifibatide (two boluses, each containing 180 microg per kilogram of body weight, administered 10 minutes apart, and a standard infusion > or = 12 hours before angiography) or a matching placebo infusion with provisional use of eptifibatide after angiography (delayed eptifibatide). The primary efficacy end point was a composite of death, myocardial infarction, recurrent ischemia requiring urgent revascularization, or the occurrence of a thrombotic complication during percutaneous coronary intervention that required bolus therapy opposite to the initial study-group assignment ("thrombotic bailout") at 96 hours. The key secondary end point was a composite of death or myocardial infarction within the first 30 days. Key safety end points were bleeding and the need for transfusion within the first 120 hours after randomization.

RESULTS:

The primary end point occurred in 9.3% of patients in the early-eptifibatide group and in 10.0% in the delayed-eptifibatide group (odds ratio, 0.92; 95% confidence interval [CI], 0.80 to 1.06; P=0.23). At 30 days, the rate of death or myocardial infarction was 11.2% in the early-eptifibatide group, as compared with 12.3% in the delayed-eptifibatide group (odds ratio, 0.89; 95% CI, 0.79 to 1.01; P=0.08). Patients in the early-eptifibatide group had significantly higher rates of bleeding and red-cell transfusion. There was no significant difference between the two groups in rates of severe bleeding or nonhemorrhagic serious adverse events.

CONCLUSIONS:

In patients who had acute coronary syndromes without ST-segment elevation, the use of eptifibatide 12 hours or more before angiography was not superior to the provisional use of eptifibatide after angiography. The early use of eptifibatide was associated with an increased risk of non-life-threatening bleeding and need for transfusion. (ClinicalTrials.gov number, NCT00089895.)

• Authors: Robert P Giugliano, Jennifer A White, Christoph Bode, Paul W Armstrong, Gilles Montalescot, Basil S Lewis, Arnoud van 't Hof, Lisa G Berdan, Kerry L Lee, John T Strony, Steven Hildemann, Enrico Veltri, Frans Van de Werf, Eugene Braunwald, Robert A Harrington, Robert M Califf, L Kristin Newby, EARLY ACS Investigators
• Journal: The New England journal of medicine (N Engl J Med) Vol. 360 Issue 21 Pg. 2176-90 (May 21 2009) ISSN: 1533-4406 [Electronic] United States
• PMID: 19332455 (Publication Type: Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: 2009 Massachusetts Medical Society

Chemical References

• Peptides
• Platelet Aggregation Inhibitors
• Platelet Glycoprotein GPIIb-IIIa Complex
• Eptifibatide

Topics

• Acute Coronary Syndrome (drug therapy, mortality, therapy)
• Aged
• Angina Pectoris (therapy)
• Angioplasty, Balloon, Coronary
• Combined Modality Therapy
• Coronary Angiography
• Coronary Artery Bypass
• Drug Administration Schedule
• Drug Therapy, Combination
• Electrocardiography
• Eptifibatide
• Female
• Hemorrhage (chemically induced)
• Humans
• Infusions, Intravenous
• Kaplan-Meier Estimate
• Male
• Middle Aged
• Myocardial Infarction (epidemiology, therapy)
• Odds Ratio
• Peptides (administration & dosage, adverse effects)
• Platelet Aggregation Inhibitors (administration & dosage, adverse effects)
• Platelet Glycoprotein GPIIb-IIIa Complex (antagonists & inhibitors)
• Thrombosis (epidemiology, prevention & control)
• Treatment Failure