Context: Enoxaparin has demonstrated advantages over unfractionated hep arin in low-to moderate-risk patients with non-ST-segment elevation acute coronary syndromes (ACS) treated with a conservative strategy. Objectiv...Context: Enoxaparin has demonstrated advantages over unfractionated hep arin in low-to moderate-risk patients with non-ST-segment elevation acute coronary syndromes (ACS) treated with a conservative strategy. Objectives: To compare the outcomes of patients treated with enoxaparin vs unfractionated hep arin and to define the role of enoxaparin in patients with non-ST-segment elev ation ACS at high risk for ischemic cardiac complications managed with an early invasive approach. Design, Setting, and Participants: The Superior Yield of the New Strategy of Enoxaparin, Revascularization and Glycoprotein IIb/IIIa Inhibito rs (SYNERGY) trial was a prospective, randomized, open-label, multicenter, inte rnational trial conducted between August 2001 and December 2003. A total of 1002 7 high-risk patients with non-ST-segment elevation ACS to be treated with an intended early invasive strategy were recruited. Interventions: Subcutaneous eno xaparin (n=4993) or intravenous unfractionated heparin (n=4985) was to be admini stered immediately after enrollment and continued until the patient required no further anticoagulation, as judged by the treating physician. Main Outcome Measu res: The primary efficacy outcome was the composite clinical end point of all-c ause death or nonfatal myocardial infarction during the first 30 days after rand omization. The primary safety outcome was major bleeding or stroke. Results: The primary end point occurred in 14.0%(696/4993) of patients assigned to enoxapar in and 14.5%(722/4985) of patients assigned to unfractionated heparin (odds rat io <<OR>>, 0.96; 95%confidence interval <<CI>>, 0.86-1,06). No differences in isch emic events during percutaneous coronary intervention (PCI) were observed betwee n enoxaparin and unfractionated heparin groups, respectively, including similar rates of abrupt closure (31/2321 <<1.3%>> vs 40/2364 <<1.7%>>), threatened abrupt closure (25/2321 <<1.1%>> vs 24/2363 <<1.0%>>), unsuccessful PCI (81/2281 <<3.6%>> vs 79/ 2328 <<3.4%>>), or emergency coronary artery bypass graft surgery (6/2323 <<0.3%>> vs 8/2363 <<0.3%>>). More bleeding was observed with enoxaparin, with a s tatistically significant increase in TIMI (Thrombolysis in Myocardial Infarction ) major bleeding (9.1%vs 7.6%, P=.008) but nonsignificant excess in GUSTO (Glo bal Utilization of Streptokinase and t-PA for Occluded Arteries) severe bleedin g (2.7%vs 2.2%, P=.08) and transfusions (17.0%vs 16.0%, P=.16). Conclusions: Enoxaparin was not superior to unfractionated heparin but was non-inferior for the treatment of high-risk patients with non-ST-segment elevation ACS. Enoxa parin is a safe and effective alternative to unfractionated heparin and the adva ntages of convenience should be balanced with the modest excess of major bleedin g.展开更多
Background: The COMplement inhibition in Myocardial infarction treated with Angioplasty(COMMA) trial previously demonstrated an unexpected dose-dependent reduction in 90-day mortality after bolus/infusion of pexelizum...Background: The COMplement inhibition in Myocardial infarction treated with Angioplasty(COMMA) trial previously demonstrated an unexpected dose-dependent reduction in 90-day mortality after bolus/infusion of pexelizumab despite no reduction in the primary end point of myocardial infarction(MI) size. We examined whether the mortality benefit was related to established modulators of clinical benefit such as baseline demographics, time to treatment from symptom onset, myocardial perfusion post-percutan-eous coronary intervention(PCI), and extent of ST resolution. Methods and Results: Eight hundred fourteen patients were randomized into 3 groups;(1) placebo,(2) pexelizumab bolus 2.0 mg/kg and placebo infusion for 20 hours, and(3) pexelizumab bolus 2.0 and 0.05 mg/kg per hour infusion for 20 hours commencing 4 hours after the bolus. Subjects presented with ST elevation MI within 6 hours of symptom onset and underwent PCI, creatine kinase(CK), and CK-MB measurements taken sequentially to define CK-MB area under the curve(AUC) and sequential ECG’s defined ST resolution and QRS infarct size. Whereas mortality for both placebo and bolus pexelizumab groups rose during later time after presentation, it remained low and did not change appreciably during the 6-hour randomization window when patients received pexelizumab bolus infusion. Amplification of the mortality benefit was evident in patients with the highest quartile of hemodynamic compromise, that is, heart rate ≥90 beat/min and systolic blood pressure ≤118 mm Hg(3.2%vs 11.3%P=.004). A significant interaction between treatment assignment and hemodynamic status(P=.013) existed after adjusting for age, race, and MI location. Clinical benefit was not related to infarct size, extent of ST elevation, or evidence of angiographic or electrocardiographic reperfusion. Conclusions: These data raise the possibility that the clinical benefit of pexelizumab is mediated through novel pathways such as reduction in apoptosis or other mechanisms.展开更多
文摘Context: Enoxaparin has demonstrated advantages over unfractionated hep arin in low-to moderate-risk patients with non-ST-segment elevation acute coronary syndromes (ACS) treated with a conservative strategy. Objectives: To compare the outcomes of patients treated with enoxaparin vs unfractionated hep arin and to define the role of enoxaparin in patients with non-ST-segment elev ation ACS at high risk for ischemic cardiac complications managed with an early invasive approach. Design, Setting, and Participants: The Superior Yield of the New Strategy of Enoxaparin, Revascularization and Glycoprotein IIb/IIIa Inhibito rs (SYNERGY) trial was a prospective, randomized, open-label, multicenter, inte rnational trial conducted between August 2001 and December 2003. A total of 1002 7 high-risk patients with non-ST-segment elevation ACS to be treated with an intended early invasive strategy were recruited. Interventions: Subcutaneous eno xaparin (n=4993) or intravenous unfractionated heparin (n=4985) was to be admini stered immediately after enrollment and continued until the patient required no further anticoagulation, as judged by the treating physician. Main Outcome Measu res: The primary efficacy outcome was the composite clinical end point of all-c ause death or nonfatal myocardial infarction during the first 30 days after rand omization. The primary safety outcome was major bleeding or stroke. Results: The primary end point occurred in 14.0%(696/4993) of patients assigned to enoxapar in and 14.5%(722/4985) of patients assigned to unfractionated heparin (odds rat io <<OR>>, 0.96; 95%confidence interval <<CI>>, 0.86-1,06). No differences in isch emic events during percutaneous coronary intervention (PCI) were observed betwee n enoxaparin and unfractionated heparin groups, respectively, including similar rates of abrupt closure (31/2321 <<1.3%>> vs 40/2364 <<1.7%>>), threatened abrupt closure (25/2321 <<1.1%>> vs 24/2363 <<1.0%>>), unsuccessful PCI (81/2281 <<3.6%>> vs 79/ 2328 <<3.4%>>), or emergency coronary artery bypass graft surgery (6/2323 <<0.3%>> vs 8/2363 <<0.3%>>). More bleeding was observed with enoxaparin, with a s tatistically significant increase in TIMI (Thrombolysis in Myocardial Infarction ) major bleeding (9.1%vs 7.6%, P=.008) but nonsignificant excess in GUSTO (Glo bal Utilization of Streptokinase and t-PA for Occluded Arteries) severe bleedin g (2.7%vs 2.2%, P=.08) and transfusions (17.0%vs 16.0%, P=.16). Conclusions: Enoxaparin was not superior to unfractionated heparin but was non-inferior for the treatment of high-risk patients with non-ST-segment elevation ACS. Enoxa parin is a safe and effective alternative to unfractionated heparin and the adva ntages of convenience should be balanced with the modest excess of major bleedin g.
文摘Background: The COMplement inhibition in Myocardial infarction treated with Angioplasty(COMMA) trial previously demonstrated an unexpected dose-dependent reduction in 90-day mortality after bolus/infusion of pexelizumab despite no reduction in the primary end point of myocardial infarction(MI) size. We examined whether the mortality benefit was related to established modulators of clinical benefit such as baseline demographics, time to treatment from symptom onset, myocardial perfusion post-percutan-eous coronary intervention(PCI), and extent of ST resolution. Methods and Results: Eight hundred fourteen patients were randomized into 3 groups;(1) placebo,(2) pexelizumab bolus 2.0 mg/kg and placebo infusion for 20 hours, and(3) pexelizumab bolus 2.0 and 0.05 mg/kg per hour infusion for 20 hours commencing 4 hours after the bolus. Subjects presented with ST elevation MI within 6 hours of symptom onset and underwent PCI, creatine kinase(CK), and CK-MB measurements taken sequentially to define CK-MB area under the curve(AUC) and sequential ECG’s defined ST resolution and QRS infarct size. Whereas mortality for both placebo and bolus pexelizumab groups rose during later time after presentation, it remained low and did not change appreciably during the 6-hour randomization window when patients received pexelizumab bolus infusion. Amplification of the mortality benefit was evident in patients with the highest quartile of hemodynamic compromise, that is, heart rate ≥90 beat/min and systolic blood pressure ≤118 mm Hg(3.2%vs 11.3%P=.004). A significant interaction between treatment assignment and hemodynamic status(P=.013) existed after adjusting for age, race, and MI location. Clinical benefit was not related to infarct size, extent of ST elevation, or evidence of angiographic or electrocardiographic reperfusion. Conclusions: These data raise the possibility that the clinical benefit of pexelizumab is mediated through novel pathways such as reduction in apoptosis or other mechanisms.
