Routine upstream initiation vs deferred selective use of glycoprotein IIb/IIIa inhibitors in acute coronary syndromes: the ACUITY Timing trial.
BACKGROUND
In patients with moderate- and high-risk acute coronary syndromes (ACS) who undergo an early, invasive treatment strategy, current guidelines recommend administration of platelet glycoprotein IIb/IIIa (Gp IIb/IIIa) inhibitors, either upstream to all patients prior to angiography or deferred for selective use in the catheterization laboratory just prior to angioplasty. The preferred approach is undetermined.


OBJECTIVE
To determine the optimal strategy for the use of Gp IIb/IIIa inhibitors in patients with moderate- and high-risk ACS undergoing an early, invasive treatment strategy.


METHODS
Prospective, randomized, open-label trial with 30-day clinical follow-up.


METHODS
Four hundred fifty academic and community-based institutions in 17 countries.


METHODS
A total of 9207 patients with moderate- and high-risk ACS undergoing an invasive treatment strategy.


METHODS
Patients were randomly assigned to receive either routine upstream (n=4605) or deferred selective (n=4602) Gp IIb/IIIa inhibitor administration, respectively.


METHODS
The primary outcome was assessment of noninferiority of deferred Gp IIb/IIIa inhibitor use compared with upstream administration for the prevention of composite ischemic events (death, myocardial infarction, or unplanned revascularization for ischemia) at 30 days, using a 1-sided alpha level of .025. Major secondary end points included noninferiority or superiority of major bleeding and net clinical outcomes (composite ischemia or major bleeding).


RESULTS
Glycoprotein IIb/IIIa inhibitors were used more frequently (98.3% vs 55.7%, respectively) and for a significantly longer duration (median, 18.3 vs 13.1 hours; P<.001) in patients in the upstream group compared with the deferred group. Composite ischemia at 30 days occurred in 7.9% of patients assigned to deferred use compared with 7.1% of patients assigned to upstream administration (relative risk, 1.12; 95% confidence interval, 0.97-1.29; P = .044 for noninferiority; P = .13 for superiority); as such, the criterion for noninferiority was not met. Deferred use compared with upstream use resulted in reduced 30-day rates of major bleeding (4.9% vs 6.1%, respectively; P<.001 for noninferiority; P = .009 for superiority) and similar rates of net clinical outcomes (11.7% vs 11.7%; P<.001 for noninferiority; P = .93 for superiority).


CONCLUSIONS
Among patients with moderate- and high-risk ACS undergoing an invasive treatment strategy, deferring the routine upstream use of Gp IIb/IIIa inhibitors for selective administration in the cardiac catheterization laboratory only to patients undergoing percutaneous coronary intervention resulted in a numerical increase in composite ischemia that, while not statistically significant, did not meet the criterion for noninferiority. This finding was offset by a significant reduction in major bleeding.


BACKGROUND
ClinicalTrials.gov Identifier: NCT00093158.
Stone
Gregg W
GW
Columbia University Medical Center and the Cardiovascular Research Foundation, New York, NY 10022, USA. gs2184@columbia.edu
Bertrand
Michel E
ME
Moses
Jeffrey W
JW
Ohman
E Magnus
EM
Lincoff
A Michael
AM
Ware
James H
JH
Pocock
Stuart J
SJ
McLaurin
Brent T
BT
Cox
David A
DA
Jafar
M Zubair
MZ
Chandna
Harish
H
Hartmann
Franz
F
Leisch
Franz
F
Strasser
Ruth H
RH
Desaga
Martin
M
Stuckey
Thomas D
TD
Zelman
Richard B
RB
Lieber
Ira H
IH
Cohen
David J
DJ
Mehran
Roxana
R
White
Harvey D
HD
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000789:Angina, Unstable / Q000188:drug therapy* / Q000628:therapy; D015906:Angioplasty, Balloon, Coronary; D000925:Anticoagulants / Q000627:therapeutic use; D006328:Cardiac Catheterization; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000628:therapy; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage* / Q000627:therapeutic use; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors*; D011446:Prospective Studies
D000925:Anticoagulants; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex