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
Background: Previous reports have associated acute coronary syndromes(ACSs) with cerebrovascular disease but in general have not included long- term patient follow- up or have not analyzed ischemic and hemorrhagic cer...Background: Previous reports have associated acute coronary syndromes(ACSs) with cerebrovascular disease but in general have not included long- term patient follow- up or have not analyzed ischemic and hemorrhagic cerebrovascular events separately. Methods: We analyzed stroke outcomes from the OPUS- TIMI 16 study, a multicenter, randomized, placebo- controlled trial. Patients were randomized to aspirin plus either orbofiban or placebo and followed for up to 1 year. Cerebrovascular events were prospectively identified and classified by a committee of cardiologists and neurologists blinded to treatment assignment. Results: During 10 months of follow- up, there were 150(1.5% ) patients with cerebrovascular events. Risk factors for ischemic stroke(n=67) and transient ischemic attack(TIA)(n=44) were age, prior ischemic stroke, history of hypertension, and increased heart rate. Prior ischemic stroke and history of hypertension were not risk factors for 30- day ischemic stroke or TIA. Risk factors for intracranial hemorrhage(ICH)(n=14) were age, history of hypertension, history of TIA, and coronary angiography with evidence of coronary artery disease. Compared with placebo, treatment with orbofiban was associated with a nonsignificant increased risk of ischemic stroke or TIA(HR 1.15, 95% CI 0.76- 1.74, P=.51)and ICH(HR 1.25, 95% CI 0.39- 4.00, P=.70). Conclusions: The overall incidence of cerebrovascular events after ACS was highest in the first 30 days then declined; risk factors for cerebrovascular events may be different in the different periods. Orbofiban, despite no significant excess risk of ICH, was not effective in preventing ischemic stroke or TIA.展开更多
Background: Although fibrinolysis is effective in improving outcomes in ST- elevation myocardial infarction(STEMI), failure to achieve reperfusion and/or reocclusion of the infarct- related artery occur in substantial...Background: Although fibrinolysis is effective in improving outcomes in ST- elevation myocardial infarction(STEMI), failure to achieve reperfusion and/or reocclusion of the infarct- related artery occur in substantial proportions of patients during their index hospitalization and are associated with a significant increase in mortality. We hypothesize that the addition of clopidogrel to standard fibrinolytic therapy in patients with acute STEMI will improve reperfusion. Study design: CLARITY- TIMI 28 is a multicenter, international, randomized, double- blind, placebo- contro- lled trial designed to examine the efficacy and safety of clopidogrel when added to standard adjuvant therapy for fibrinolysis. The primary efficacy end point is the composite of an occluded infarct- related artery(defined as TIMI flow grade 0 or 1) on the predischarge angiogram or death or a recurrent myocardial infarction(MI) up to the start of coronary angiography. For subjects who do not undergo angiography, occurrence of death or recurrent MI by day 8 or by hospital discharge, whichever comes first, is used. The primary safety assessment is TIMI major bleeding. Secondary end points include ST resolution at 180 minutes and the clinical composite of death, MI, or recurrent ischemia. Substudies include analyses of biomarkers, DNA, continuous electrocardiogram monitoring, and initiation of treatment in the ambulance. Conclusions: CLARITY- TIMI 28 will help to define the role of clopidogrel as part of the pharmacologic reperfusion regimen for acute STEMI.展开更多
Background: Early cardiac catheterization has been shown to improve outcomes in patients with non- ST- elevation acute coronary syndromes but not yet in those with ST- elevation myocardial infarction(STEMI). The benef...Background: Early cardiac catheterization has been shown to improve outcomes in patients with non- ST- elevation acute coronary syndromes but not yet in those with ST- elevation myocardial infarction(STEMI). The benefit of catheterization in both syndromes may depend on patient risk for adverse clinical outcomes. Methods: We analyzed the relation between inhospital catheterization and subsequent clinical outcomes based on risk profile in 8286 patients in the OPUS- TIMI 16 Trial of patients with acute coronary syndromes. Using baseline clinical characteristics, patients were stratified into low- , intermediate- , and high- risk groups. The primary end point was 10- month mortality. The STEMI, non- STEMI(NSTEMI), and unstable angina subgroups were analyzed separately. Results: Inhospital cardiac catheterization was performed in 44% of patients. Mortality rates at 10 months were 1.3% , 2.2% , and 11.3% in the low- , intermediate- , and high- risk groups, respectively. Inhospital cardiac catheterization was associated with a trend to lower mortality among the high- risk patients with STEMI(hazard ratios[HR] 0.57, 95% CI 0.33- 1.01, P=.052) and NSTEMI(HR 0.65, 95% CI 0.39- 1.07, P=.088) but not in those with unstable angina(HR 0.95, 95% CI 0.63- 1.43, P=.82). Catheterization was not associated with any significant difference in mortality in the low- risk or intermediate- risk group. The differences among high- risk patients persisted after adjusting for baseline characteristics; inhospital catheterization was associated with significantly lower mortality in high- risk patients with ST and non- ST myocardial infarction(HR 0.65, 95% CI 0.45- 0.95, P=.03). Conclusions: Inhospital cardiac catheterization is associated with lower mortality in high- risk patients and no difference in mortality in low- risk and intermediate- risk patients after STEMI and NSTEMI. These data support the hypothesis that high- risk patients with either STEMI or NSTEMI may benefit from an early invasive strategy. New prospective randomized trials are warranted, particularly in the STEMI population.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Background: Previous reports have associated acute coronary syndromes(ACSs) with cerebrovascular disease but in general have not included long- term patient follow- up or have not analyzed ischemic and hemorrhagic cerebrovascular events separately. Methods: We analyzed stroke outcomes from the OPUS- TIMI 16 study, a multicenter, randomized, placebo- controlled trial. Patients were randomized to aspirin plus either orbofiban or placebo and followed for up to 1 year. Cerebrovascular events were prospectively identified and classified by a committee of cardiologists and neurologists blinded to treatment assignment. Results: During 10 months of follow- up, there were 150(1.5% ) patients with cerebrovascular events. Risk factors for ischemic stroke(n=67) and transient ischemic attack(TIA)(n=44) were age, prior ischemic stroke, history of hypertension, and increased heart rate. Prior ischemic stroke and history of hypertension were not risk factors for 30- day ischemic stroke or TIA. Risk factors for intracranial hemorrhage(ICH)(n=14) were age, history of hypertension, history of TIA, and coronary angiography with evidence of coronary artery disease. Compared with placebo, treatment with orbofiban was associated with a nonsignificant increased risk of ischemic stroke or TIA(HR 1.15, 95% CI 0.76- 1.74, P=.51)and ICH(HR 1.25, 95% CI 0.39- 4.00, P=.70). Conclusions: The overall incidence of cerebrovascular events after ACS was highest in the first 30 days then declined; risk factors for cerebrovascular events may be different in the different periods. Orbofiban, despite no significant excess risk of ICH, was not effective in preventing ischemic stroke or TIA.
文摘Background: Although fibrinolysis is effective in improving outcomes in ST- elevation myocardial infarction(STEMI), failure to achieve reperfusion and/or reocclusion of the infarct- related artery occur in substantial proportions of patients during their index hospitalization and are associated with a significant increase in mortality. We hypothesize that the addition of clopidogrel to standard fibrinolytic therapy in patients with acute STEMI will improve reperfusion. Study design: CLARITY- TIMI 28 is a multicenter, international, randomized, double- blind, placebo- contro- lled trial designed to examine the efficacy and safety of clopidogrel when added to standard adjuvant therapy for fibrinolysis. The primary efficacy end point is the composite of an occluded infarct- related artery(defined as TIMI flow grade 0 or 1) on the predischarge angiogram or death or a recurrent myocardial infarction(MI) up to the start of coronary angiography. For subjects who do not undergo angiography, occurrence of death or recurrent MI by day 8 or by hospital discharge, whichever comes first, is used. The primary safety assessment is TIMI major bleeding. Secondary end points include ST resolution at 180 minutes and the clinical composite of death, MI, or recurrent ischemia. Substudies include analyses of biomarkers, DNA, continuous electrocardiogram monitoring, and initiation of treatment in the ambulance. Conclusions: CLARITY- TIMI 28 will help to define the role of clopidogrel as part of the pharmacologic reperfusion regimen for acute STEMI.
文摘Background: Early cardiac catheterization has been shown to improve outcomes in patients with non- ST- elevation acute coronary syndromes but not yet in those with ST- elevation myocardial infarction(STEMI). The benefit of catheterization in both syndromes may depend on patient risk for adverse clinical outcomes. Methods: We analyzed the relation between inhospital catheterization and subsequent clinical outcomes based on risk profile in 8286 patients in the OPUS- TIMI 16 Trial of patients with acute coronary syndromes. Using baseline clinical characteristics, patients were stratified into low- , intermediate- , and high- risk groups. The primary end point was 10- month mortality. The STEMI, non- STEMI(NSTEMI), and unstable angina subgroups were analyzed separately. Results: Inhospital cardiac catheterization was performed in 44% of patients. Mortality rates at 10 months were 1.3% , 2.2% , and 11.3% in the low- , intermediate- , and high- risk groups, respectively. Inhospital cardiac catheterization was associated with a trend to lower mortality among the high- risk patients with STEMI(hazard ratios[HR] 0.57, 95% CI 0.33- 1.01, P=.052) and NSTEMI(HR 0.65, 95% CI 0.39- 1.07, P=.088) but not in those with unstable angina(HR 0.95, 95% CI 0.63- 1.43, P=.82). Catheterization was not associated with any significant difference in mortality in the low- risk or intermediate- risk group. The differences among high- risk patients persisted after adjusting for baseline characteristics; inhospital catheterization was associated with significantly lower mortality in high- risk patients with ST and non- ST myocardial infarction(HR 0.65, 95% CI 0.45- 0.95, P=.03). Conclusions: Inhospital cardiac catheterization is associated with lower mortality in high- risk patients and no difference in mortality in low- risk and intermediate- risk patients after STEMI and NSTEMI. These data support the hypothesis that high- risk patients with either STEMI or NSTEMI may benefit from an early invasive strategy. New prospective randomized trials are warranted, particularly in the STEMI population.
