BACKGROUND: A substantial proportion of patients receiving fibrinolytic therapy for myocardial infarction with ST-segment elevation have inadequate reperfusion or reocclusion of the infarct-related artery, leading to ...BACKGROUND: A substantial proportion of patients receiving fibrinolytic therapy for myocardial infarction with ST-segment elevation have inadequate reperfusion or reocclusion of the infarct-related artery, leading to an increased risk of complications and death. METHODS: We enrolled 3491 patients, 18 to 75 years of age, who presented within 12 hours after the onset of an ST-elevation myocardial infarction and randomly assigned them to receive clopidogrel(300-mg loading dose, followed by 75 mg once daily) or placebo. Patients received a fibrinolytic agent, aspirin, and when appropriate, heparin(dispensed according to body weight) and were scheduled to undergo angiography 48 to 192 hours after the start of study medication. The primary efficacy end point was a composite of an occluded infarct-related artery(defined by a Thrombolysis in Myocardial Infarction flow grade of 0 or 1) on angiography or death or recurrent myocardial infarction before angiography. RESULTS: The rates of the primary efficacy end point were 21.7 percent in the placebo group and 15.0 percent in the clopidogrel group, representing an absolute reduction of 6.7 percentage points in the rate and a 36 percent reduction in the odds of the end point with clopidogrel therapy(95 percent confidence interval, 24 to 47 percent; P< 0.001). By 30 days, clopidogrel therapy reduced the odds of the composite end point of death from cardiovascular causes, recurrent myocardial infarction, or recurrent ischemia leading to the need for urgent revascularization by 20 percent(from 14.1 to 11.6 percent, P=0.03). The rates of major bleeding and intracranial hemorrhage were similar in the two groups. CONCLUSIONS: In patients 75 years of age or younger who have myocardial infarction with ST-segment elevation and who receive aspirin and a standard fibrinolytic regimen, the addition of clopidogrel improves the patency rate of the infarct-related artery and reduces ischemic complications.展开更多
The aim of this study was to evaluate the pharmacogenetic role of the factor XIII(FXIII)valine 34 leucine(Val34Leu)polymorphism in the fibrinolytic therapy of acute myocardial infarction(MI). Fibrinolytic therapy is a...The aim of this study was to evaluate the pharmacogenetic role of the factor XIII(FXIII)valine 34 leucine(Val34Leu)polymorphism in the fibrinolytic therapy of acute myocardial infarction(MI). Fibrinolytic therapy is an established treatment for acute MI, but up to 40%of treated patients do not achieve optimal tissue reperfusion. The FXIII Val34Leu polymorphism is one of the most relevant functional polymorphisms described in the haemostatic system. The common Leu34 allele associates with an increased FXIII-transglutaminase activity, which results in an increased and faster rate of fibrin stabilization. We genotyped this polymorphism in 293 consecutive MI patients(62±12 years; 231 males)from two different European populations. All patients were treated with standard doses of fibrinolytic drugs. Noninvasive assessment of the efficacy of coronary fibrinolysis was evaluated by serial electrocardiograms and creatine kinase time-activity curves. The clinical outcome was also re-evaluated at 24 h(death, reinfarction, or urgent revascularization). Multivariate analysis showed that Leu34 carriers displayed a significantly less efficient fibrinolysis than carriers of Val/Val genotype(p=0.021; odds ratio [OR] 1.90, 95%confidence interval [CI] 1.10 to 3.28). At 24 h, Leu34 allele carriers had the worst outcome(p=0.006; OR 2.14, 95%CI 1.25 to 3.68). Interestingly, the combination of the Leu34 allele and nonsmoking status increased the risk of non-reperfusion criteria(p=0.003, OR 3.77), and worse outcomes at 24 h(p=0.001, OR 4.55). In a large cohort of nonselected and consecutive acute MI patients from two different European populations, we show clinical evidence that the presence of the Leu34 allele reduces the efficacy of fibrinolytic therapy.展开更多
文摘BACKGROUND: A substantial proportion of patients receiving fibrinolytic therapy for myocardial infarction with ST-segment elevation have inadequate reperfusion or reocclusion of the infarct-related artery, leading to an increased risk of complications and death. METHODS: We enrolled 3491 patients, 18 to 75 years of age, who presented within 12 hours after the onset of an ST-elevation myocardial infarction and randomly assigned them to receive clopidogrel(300-mg loading dose, followed by 75 mg once daily) or placebo. Patients received a fibrinolytic agent, aspirin, and when appropriate, heparin(dispensed according to body weight) and were scheduled to undergo angiography 48 to 192 hours after the start of study medication. The primary efficacy end point was a composite of an occluded infarct-related artery(defined by a Thrombolysis in Myocardial Infarction flow grade of 0 or 1) on angiography or death or recurrent myocardial infarction before angiography. RESULTS: The rates of the primary efficacy end point were 21.7 percent in the placebo group and 15.0 percent in the clopidogrel group, representing an absolute reduction of 6.7 percentage points in the rate and a 36 percent reduction in the odds of the end point with clopidogrel therapy(95 percent confidence interval, 24 to 47 percent; P< 0.001). By 30 days, clopidogrel therapy reduced the odds of the composite end point of death from cardiovascular causes, recurrent myocardial infarction, or recurrent ischemia leading to the need for urgent revascularization by 20 percent(from 14.1 to 11.6 percent, P=0.03). The rates of major bleeding and intracranial hemorrhage were similar in the two groups. CONCLUSIONS: In patients 75 years of age or younger who have myocardial infarction with ST-segment elevation and who receive aspirin and a standard fibrinolytic regimen, the addition of clopidogrel improves the patency rate of the infarct-related artery and reduces ischemic complications.
文摘The aim of this study was to evaluate the pharmacogenetic role of the factor XIII(FXIII)valine 34 leucine(Val34Leu)polymorphism in the fibrinolytic therapy of acute myocardial infarction(MI). Fibrinolytic therapy is an established treatment for acute MI, but up to 40%of treated patients do not achieve optimal tissue reperfusion. The FXIII Val34Leu polymorphism is one of the most relevant functional polymorphisms described in the haemostatic system. The common Leu34 allele associates with an increased FXIII-transglutaminase activity, which results in an increased and faster rate of fibrin stabilization. We genotyped this polymorphism in 293 consecutive MI patients(62±12 years; 231 males)from two different European populations. All patients were treated with standard doses of fibrinolytic drugs. Noninvasive assessment of the efficacy of coronary fibrinolysis was evaluated by serial electrocardiograms and creatine kinase time-activity curves. The clinical outcome was also re-evaluated at 24 h(death, reinfarction, or urgent revascularization). Multivariate analysis showed that Leu34 carriers displayed a significantly less efficient fibrinolysis than carriers of Val/Val genotype(p=0.021; odds ratio [OR] 1.90, 95%confidence interval [CI] 1.10 to 3.28). At 24 h, Leu34 allele carriers had the worst outcome(p=0.006; OR 2.14, 95%CI 1.25 to 3.68). Interestingly, the combination of the Leu34 allele and nonsmoking status increased the risk of non-reperfusion criteria(p=0.003, OR 3.77), and worse outcomes at 24 h(p=0.001, OR 4.55). In a large cohort of nonselected and consecutive acute MI patients from two different European populations, we show clinical evidence that the presence of the Leu34 allele reduces the efficacy of fibrinolytic therapy.
