BACKGROUND: The combined use of anticoagulants, antiplatelet agents, and invasive coronary procedures reduces ischemic coronary events but also increases bleeding in patients with acute coronary syndromes. We therefor...BACKGROUND: The combined use of anticoagulants, antiplatelet agents, and invasive coronary procedures reduces ischemic coronary events but also increases bleeding in patients with acute coronary syndromes. We therefore assessed whether fondaparinux would preserve the anti-ischemic benefits of enoxaparin while reducing bleeding. METHODS: We randomly assigned 20,078 patients with acute coronary syndromes to receive either fondaparinux(2.5 mg daily) or enoxaparin(1 mg per kilogram of body weight twice daily) for a mean of six days and evaluated death, myocardial infarction, or refractory ischemia at nine days(the primary outcome); major bleeding; and their combination. Patients were followed for up to six months. RESULTS: The number of patients with primary outcome events was similar in the two groups(579 with fondaparinux[5.8 percent] vs. 573 with enoxaparin[5.7 percent]; hazard ratio in the fondaparinux group, 1.01; 95 percent confidence interval, 0.90 to 1.13), satisfying the noninferiority criteria. The number of events meeting this combined outcome showed a nonsignificant trend toward a lower value in the fondaparinux group at 30 days(805 vs. 864, P=0.13) and at the end of the study(1222 vs. 1308, P=0.06). The rate of major bleeding at nine days was markedly lower with fondaparinux than with enoxaparin(217 events[2.2 percent] vs. 412 events[4.1 percent]; hazard ratio, 0.52; P< 0.001). The composite of the primary outcome and major bleeding at nine days favored fondaparinux(737 events[7.3 percent] vs. 905 events[9.0 percent]; hazard ratio, 0.81; P< 0.001). Fondaparinux was associated with a significantly reduced number of deaths at 30 days(295 vs. 352, P=0.02) and at 180 days(574 vs. 638, P=0.05). CONCLUSIONS: Fondaparinux is similar to enoxaparin in reducing the risk of ischemic events at nine days, but it substantially reduces major bleeding and improves long term mortality and morbidity.展开更多
Context: Glucose-insulin-potassium(GIK) infusion is a widely applicable, low-cost therapy that has been postulated to improve mortality in patients with acute ST segment elevation myocardial infarction(STEMI). Given t...Context: Glucose-insulin-potassium(GIK) infusion is a widely applicable, low-cost therapy that has been postulated to improve mortality in patients with acute ST segment elevation myocardial infarction(STEMI). Given the potential global importance of GIK infusion, a large, adequately powered randomized trial is required to determine the effect of GIK on mortality in patients with STEMI. Objective: To determine the effect of high-dose GIK infusion on mortality in patients with STEMI. Design, Setting, and Participants: Randomized controlled trial conducted in 470 centers worldwide among 20201 patients with STEMI who presented within 12 hours of symptom onset. The mean age of patients was 58.6 years, and evidence based therapies were commonly used. Intervention: Patients were randomly assigned to receive GIK intravenous infusion for 24 hours plus usual care(n=10091) or to receive usual care alone(controls; n=10110). Main Outcome Measures: Mortality, cardiac arrest, cardiogenic shock, and reinfarction at 30 days after randomization. Results: At 30 days, 976 control patients(9.7%) and 1004 GIK infusion patients(10.0%) died(hazard ratio [HR], 1.03; 95%confidence interval [CI], 0.95-1.13; P=.45)-. There were no significant differences in the rates of cardiac arrest(1.5%[151/10107] in control and 1.4%[139/10088] in GIK infusion; HR, 0.93; 95%CI, 0.74-1.17; P=.51), cardiogenic shock(6.3%[640/10107] vs 6.6%[667/10088]; HR, 1.05; 95%CI, 0.94-1.17; P=.38), or reinfarction(2.4%[246/10107] vs 2.3%[236/10088]-; HR, 0.98; 95%CI, 0.82-1.17; P=.81). The rates of heart failure at 7 days after randomization were also similar between the groups(16.9%[1711/10107] vs 17.1%[1721/ 10088]; HR, 1.01; 95%CI, 0,95-1.08; P=.72). The lack of benefit of GIK infusion on mortality was consistent in prespecified subgroups, including in those with and without diabetes, in those presenting with and without heart failure, in those presenting early and later after symptom onset, and in those receiving and not receiving reperfusion therapy(thrombolysis or primary percutaneous coronary intervention). Conclusion: In this large, international randomized trial, high-dose GIK infusion had a neutral effect on mortality, cardiac arrest, and cardiogenic shock in patients with acute STEMI.展开更多
文摘BACKGROUND: The combined use of anticoagulants, antiplatelet agents, and invasive coronary procedures reduces ischemic coronary events but also increases bleeding in patients with acute coronary syndromes. We therefore assessed whether fondaparinux would preserve the anti-ischemic benefits of enoxaparin while reducing bleeding. METHODS: We randomly assigned 20,078 patients with acute coronary syndromes to receive either fondaparinux(2.5 mg daily) or enoxaparin(1 mg per kilogram of body weight twice daily) for a mean of six days and evaluated death, myocardial infarction, or refractory ischemia at nine days(the primary outcome); major bleeding; and their combination. Patients were followed for up to six months. RESULTS: The number of patients with primary outcome events was similar in the two groups(579 with fondaparinux[5.8 percent] vs. 573 with enoxaparin[5.7 percent]; hazard ratio in the fondaparinux group, 1.01; 95 percent confidence interval, 0.90 to 1.13), satisfying the noninferiority criteria. The number of events meeting this combined outcome showed a nonsignificant trend toward a lower value in the fondaparinux group at 30 days(805 vs. 864, P=0.13) and at the end of the study(1222 vs. 1308, P=0.06). The rate of major bleeding at nine days was markedly lower with fondaparinux than with enoxaparin(217 events[2.2 percent] vs. 412 events[4.1 percent]; hazard ratio, 0.52; P< 0.001). The composite of the primary outcome and major bleeding at nine days favored fondaparinux(737 events[7.3 percent] vs. 905 events[9.0 percent]; hazard ratio, 0.81; P< 0.001). Fondaparinux was associated with a significantly reduced number of deaths at 30 days(295 vs. 352, P=0.02) and at 180 days(574 vs. 638, P=0.05). CONCLUSIONS: Fondaparinux is similar to enoxaparin in reducing the risk of ischemic events at nine days, but it substantially reduces major bleeding and improves long term mortality and morbidity.
文摘Context: Glucose-insulin-potassium(GIK) infusion is a widely applicable, low-cost therapy that has been postulated to improve mortality in patients with acute ST segment elevation myocardial infarction(STEMI). Given the potential global importance of GIK infusion, a large, adequately powered randomized trial is required to determine the effect of GIK on mortality in patients with STEMI. Objective: To determine the effect of high-dose GIK infusion on mortality in patients with STEMI. Design, Setting, and Participants: Randomized controlled trial conducted in 470 centers worldwide among 20201 patients with STEMI who presented within 12 hours of symptom onset. The mean age of patients was 58.6 years, and evidence based therapies were commonly used. Intervention: Patients were randomly assigned to receive GIK intravenous infusion for 24 hours plus usual care(n=10091) or to receive usual care alone(controls; n=10110). Main Outcome Measures: Mortality, cardiac arrest, cardiogenic shock, and reinfarction at 30 days after randomization. Results: At 30 days, 976 control patients(9.7%) and 1004 GIK infusion patients(10.0%) died(hazard ratio [HR], 1.03; 95%confidence interval [CI], 0.95-1.13; P=.45)-. There were no significant differences in the rates of cardiac arrest(1.5%[151/10107] in control and 1.4%[139/10088] in GIK infusion; HR, 0.93; 95%CI, 0.74-1.17; P=.51), cardiogenic shock(6.3%[640/10107] vs 6.6%[667/10088]; HR, 1.05; 95%CI, 0.94-1.17; P=.38), or reinfarction(2.4%[246/10107] vs 2.3%[236/10088]-; HR, 0.98; 95%CI, 0.82-1.17; P=.81). The rates of heart failure at 7 days after randomization were also similar between the groups(16.9%[1711/10107] vs 17.1%[1721/ 10088]; HR, 1.01; 95%CI, 0,95-1.08; P=.72). The lack of benefit of GIK infusion on mortality was consistent in prespecified subgroups, including in those with and without diabetes, in those presenting with and without heart failure, in those presenting early and later after symptom onset, and in those receiving and not receiving reperfusion therapy(thrombolysis or primary percutaneous coronary intervention). Conclusion: In this large, international randomized trial, high-dose GIK infusion had a neutral effect on mortality, cardiac arrest, and cardiogenic shock in patients with acute STEMI.
