Routine upstream initiation vs deferred selective use of glycoprotein IIb/IIIa inhibitors in acute coronary syndromes: the ACUITY Timing trial.

Abstract

CONTEXT:

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.

DESIGN:

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

SETTING:

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

PATIENTS:

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

INTERVENTIONS:

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

MAIN OUTCOME MEASURES:

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.

TRIAL REGISTRATION:

ClinicalTrials.gov Identifier: NCT00093158.

• Authors: Gregg W Stone, Michel E Bertrand, Jeffrey W Moses, E Magnus Ohman, A Michael Lincoff, James H Ware, Stuart J Pocock, Brent T McLaurin, David A Cox, M Zubair Jafar, Harish Chandna, Franz Hartmann, Franz Leisch, Ruth H Strasser, Martin Desaga, Thomas D Stuckey, Richard B Zelman, Ira H Lieber, David J Cohen, Roxana Mehran, Harvey D White, ACUITY Investigators
• Journal: JAMA (JAMA) Vol. 297 Issue 6 Pg. 591-602 (Feb 14 2007) ISSN: 1538-3598 [Electronic] United States
• PMID: 17299194 (Publication Type: Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Anticoagulants
• Platelet Aggregation Inhibitors
• Platelet Glycoprotein GPIIb-IIIa Complex

Topics

• Adult
• Aged
• Aged, 80 and over
• Angina, Unstable (drug therapy, therapy)
• Angioplasty, Balloon, Coronary
• Anticoagulants (therapeutic use)
• Cardiac Catheterization
• Combined Modality Therapy
• Female
• Humans
• Kaplan-Meier Estimate
• Male
• Middle Aged
• Myocardial Infarction (drug therapy, therapy)
• Platelet Aggregation Inhibitors (administration & dosage, therapeutic use)
• Platelet Glycoprotein GPIIb-IIIa Complex (antagonists & inhibitors)
• Prospective Studies