Context: Enoxaparin or the combination of glycoprotein IIb/IIIa inhibit or tiro fiban with unfractionated heparin independently have shown superior efficacy ove r unfractionated heparin alone in patients with non-ST-e...Context: Enoxaparin or the combination of glycoprotein IIb/IIIa inhibit or tiro fiban with unfractionated heparin independently have shown superior efficacy ove r unfractionated heparin alone in patients with non-ST-elevation acute coronar y 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 a ssess efficacy and safety of the combination of enoxaparin and tirofiban compare d with unfractionated heparin and tirofiban in patients with non ST-elevation A CS. Design, Setting, and Participants: A prospective, international, open-label , randomized, noninferiority trial of 1 mg/kg of enoxaparin every 12 hours (n=20 26) compared with weight-adjusted intravenous unfractionated heparin (n=1961) i n 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 Outco me Measures: Death, recurrent myocardial infarction, or refractory ischemia at 7 days in the intent-to-treat population with boundaries set for superiority an d 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 inf arction, or refractory ischemia at 7 days compared with 184 (9.4%) of 1952 pati ents randomized to unfractionated heparin (hazard ratio <>, 0.88; 95%confiden ce interval <<CI>>, 0.71-1.08). This met the prespecified criterion for non-infe riority. All components of the composite primary and secondary end points favore d enoxaparin except death, which occurred in only 1%of patients (23 for enoxapa rin and 17 for unfractionated heparin). Rates for any TIMI grade bleeding were l ow (3.0%for enoxaparin and 2.2%for unfractionated heparin; P=.13). Using a wor st-case approach that combined 2 independent bleeding evaluations, use of enoxa parin was associated with 1 additional TIMI major bleeding episode for each 200 patients treated. Conclusions: In patients receiving tirofiban and aspirin, enox aparin 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 consis tent with prior trials performed without the use of glycoprotein IIb/IIIa inhibi tors.展开更多
文摘Context: Enoxaparin or the combination of glycoprotein IIb/IIIa inhibit or tiro fiban with unfractionated heparin independently have shown superior efficacy ove r unfractionated heparin alone in patients with non-ST-elevation acute coronar y 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 a ssess efficacy and safety of the combination of enoxaparin and tirofiban compare d with unfractionated heparin and tirofiban in patients with non ST-elevation A CS. Design, Setting, and Participants: A prospective, international, open-label , randomized, noninferiority trial of 1 mg/kg of enoxaparin every 12 hours (n=20 26) compared with weight-adjusted intravenous unfractionated heparin (n=1961) i n 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 Outco me Measures: Death, recurrent myocardial infarction, or refractory ischemia at 7 days in the intent-to-treat population with boundaries set for superiority an d 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 inf arction, or refractory ischemia at 7 days compared with 184 (9.4%) of 1952 pati ents randomized to unfractionated heparin (hazard ratio <>, 0.88; 95%confiden ce interval <<CI>>, 0.71-1.08). This met the prespecified criterion for non-infe riority. All components of the composite primary and secondary end points favore d enoxaparin except death, which occurred in only 1%of patients (23 for enoxapa rin and 17 for unfractionated heparin). Rates for any TIMI grade bleeding were l ow (3.0%for enoxaparin and 2.2%for unfractionated heparin; P=.13). Using a wor st-case approach that combined 2 independent bleeding evaluations, use of enoxa parin was associated with 1 additional TIMI major bleeding episode for each 200 patients treated. Conclusions: In patients receiving tirofiban and aspirin, enox aparin 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 consis tent with prior trials performed without the use of glycoprotein IIb/IIIa inhibi tors.
