Context Enoxaparin or the combination of glycoprotein IIb/IIIa inhibitor tirofiban
with unfractionated heparin independently have shown superior efficacy over
unfractionated heparin alone in patients with non–ST-elevation acute
coronary syndromes (ACS). It is not clear if combining enoxaparin with glycoprotein
IIb/IIIa inhibitors is as safe or as effective as the current standard combination
of unfractionated heparin with glycoprotein IIb/IIIa inhibitors.
Objective To assess efficacy and safety of the combination of enoxaparin and tirofiban
compared with unfractionated heparin and tirofiban in patients with non–ST-elevation
Design, Setting, and Participants A prospective, international, open-label, randomized, noninferiority
trial of 1 mg/kg of enoxaparin every 12 hours (n = 2026) compared with weight-adjusted
intravenous unfractionated heparin (n = 1961) in patients with non–ST-elevation
ACS receiving tirofiban and aspirin. Phase A of the A to Z trial was conducted
between December 1999 and May 2002.
Main Outcome Measures Death, recurrent myocardial infarction, or refractory ischemia at 7
days in the intent-to-treat population with boundaries set for superiority
and noninferiority. Safety based on measures of bleeding using the Thrombolysis
in Myocardial Infarction (TIMI) classification system.
Results A total of 169 (8.4%) of 2018 patients randomized to enoxaparin experienced
death, myocardial infarction, or refractory ischemia at 7 days compared with
184 (9.4%) of 1952 patients randomized to unfractionated heparin (hazard ratio
[HR], 0.88; 95% confidence interval [CI], 0.71-1.08). This met the prespecified
criterion for noninferiority. All components of the composite primary and
secondary end points favored enoxaparin except death, which occurred in only
1% of patients (23 for enoxaparin and 17 for unfractionated heparin). Rates
for any TIMI grade bleeding were low (3.0% for enoxaparin and 2.2% for unfractionated
heparin; P = .13). Using a worst-case approach that
combined 2 independent bleeding evaluations, use of enoxaparin was associated
with 1 additional TIMI major bleeding episode for each 200 patients treated.
Conclusions In patients receiving tirofiban and aspirin, enoxaparin is a suitable
alternative to unfractionated heparin for treatment of non–ST-elevation
ACS. The 12% relative and 1% absolute reductions in the primary end point
in favor of enoxaparin met criterion for noninferiority and are consistent
with prior trials performed without the use of glycoprotein IIb/IIIa inhibitors.