Early versus delayed, provisional eptifibatide in acute coronary syndromes.
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.)
Giugliano
Robert P
RP
TIMI (Thrombolysis in Myocardial Infarction) Study Group, Brigham and Women's Hospital, Boston, MA 02115, USA. rgiugliano@partners.org
White
Jennifer A
JA
Bode
Christoph
C
Armstrong
Paul W
PW
Montalescot
Gilles
G
Lewis
Basil S
BS
van 't Hof
Arnoud
A
Berdan
Lisa G
LG
Lee
Kerry L
KL
Strony
John T
JT
Hildemann
Steven
S
Veltri
Enrico
E
Van de Werf
Frans
F
Braunwald
Eugene
E
Harrington
Robert A
RA
Califf
Robert M
RM
Newby
L Kristin
LK