Antithrombotic strategies in patients with acute coronary syndromes undergoing early invasive management: one-year results from the ACUITY trial.

CONTEXT: At 30-day follow-up, patients with moderate- and high-risk acute coronary syndromes (ACS) undergoing early invasive treatment in the ACUITY trial with bivalirudin monotherapy vs heparin plus glycoprotein (GP) IIb/IIIa inhibitors had noninferior rates of adverse ischemic events with reduced rates of major bleeding. Deferred upstream use of GP IIb/IIIa inhibitors for selective administration to patients undergoing percutaneous coronary intervention (PCI) resulted in a significant reduction in major bleeding, although a small increase in composite ischemia could not be excluded. OBJECTIVE: To determine 1-year ischemic outcomes for patients in the ACUITY trial. DESIGN, SETTING, AND PATIENTS: A prospective, randomized, open-label trial with 1-year clinical follow-up at 450 academic and community-based institutions in 17 countries. A total of 13,819 patients with moderate- and high-risk ACS undergoing invasive treatment were enrolled between August 23, 2003, and December 5, 2005. INTERVENTIONS: Patients were assigned to heparin plus GP IIb/IIIa inhibitors (n = 4603), bivalirudin plus GP IIb/IIIa inhibitors (n = 4604), or bivalirudin monotherapy (n = 4612). Of these patients, 4605 were assigned to routine upstream GP IIb/IIIa administration and 4602 were deferred to selective GP IIb/IIIa inhibitor administration. MAIN OUTCOME MEASURE: Composite ischemia (death, myocardial infarction, or unplanned revascularization for ischemia) at 1 year. RESULTS: Composite ischemia at 1 year occurred in 15.4% of patients assigned to heparin plus GP IIb/IIIa inhibitors and 16.0% assigned to bivalirudin plus GP IIb/IIIa inhibitors (compared with heparin plus GP IIb/IIIa inhibitors, HR, 1.05; 95% CI, 0.95-1.16; P = .35), and 16.2% assigned to bivalirudin monotherapy (HR, 1.06; 95% CI, 0.95-1.17; P = .29). Mortality at 1 year occurred in an estimated 3.9% of patients assigned to heparin plus GP IIb/IIIa inhibitors, 3.9% assigned to bivalirudin plus GP IIb/IIIa inhibitors (HR, 0.99; 95% CI, 0.80-1.22; P = .92), and 3.8% assigned to bivalirudin monotherapy (HR, 0.96; 95% CI, 0.77-1.18; P = .67). Composite ischemia occurred in 16.3% of patients assigned to deferred use compared with 15.2% of patients assigned to upstream administration (HR, 1.08; 95% CI, 0.97-1.20; P = .15). CONCLUSIONS: At 1 year, no statistically significant difference in rates of composite ischemia or mortality among patients with moderate- and high-risk ACS undergoing invasive treatment with the 3 therapies was found. There was no statistically significant difference in the rates of composite ischemia between patients receiving routine upstream administration of GP IIb/IIIa inhibitors vs deferring their use for patients undergoing PCI. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00093158

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

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