BACKGROUND: Dual antiplatelet therapy with clopidogrel plus low-dose aspirin has not been studied in a broad population of patients at high risk for atherothrombotic events. METHODS: We randomly assigned 15,603 patien...BACKGROUND: Dual antiplatelet therapy with clopidogrel plus low-dose aspirin has not been studied in a broad population of patients at high risk for atherothrombotic events. METHODS: We randomly assigned 15,603 patients with either clinically evident cardiovascular disease or multiple risk factors to receive clopidogrel(75 mg per day) plus low-dose aspirin(75 to 162 mg per day) or placebo plus low-dose aspirin and followed them for a median of 28 months. The primary efficacy end point was a composite of myocardial infarction, stroke, or death from cardiovascular causes. RESULTS: The rate of the primary efficacy end point was 6.8 percent with clopidogrel plus aspirin and 7.3 percent with placebo plus aspirin(relative risk, 0.93; 95 percent confidence interval, 0.83 to 1.05; P=0.22). The respective rate of the principal secondary efficacy end point, which included hospitalizations for ischemic events, was 16.7 percent and 17.9 percent(relative risk, 0.92; 95 percent confidence interval, 0.86 to 0.995; P=0.04), and the rate of severe bleeding was 1.7 percent and 1.3 percent(relative risk, 1.25; 95 percent confidence interval, 0.97 to 1.61 percent; P=0.09). The rate of the primary end point among patients with multiple risk factors was 6.6 percent with clopidogrel and 5.5 percent with placebo(relative risk, 1.2; 95 percent confidence interval, 0.91 to 1.59; P=0.20) and the rate of death from cardiovascular causes also was higher with clopidogrel(3.9 percent vs. 2.2 percent, P=0.01). In the subgroup with clinically evident atherothrombosis, the rate was 6.9 percent with clopidogrel and 7.9 percent with placebo(relative risk, 0.88; 95 percent confidence interval, 0.77 to 0.998; P=0.046). CONCLUSIONS: In this trial, there was a suggestion of benefit with clopidogrel treatment in patients with symptomatic atherothrombosis and a suggestion of harm in patients with multiple risk factors. Overall, clopidogrel plus aspirin was not significantly more effective than aspirin alone in reducing the rate of myocardial infarction, stroke, or death from cardiovascular causes.展开更多
Objectives: To explore the relative and absolute risks associated with various definitions for myocardial infarction, bleeding and revascularisation within the context of percutaneous coronary intervention(PCI). Metho...Objectives: To explore the relative and absolute risks associated with various definitions for myocardial infarction, bleeding and revascularisation within the context of percutaneous coronary intervention(PCI). Methods: The REPLACE-2(randomised evaluation of PCI linking Angiomax to reduced clinical events) database of patients undergoing PCI was used. Various definitions of myocardial infarction, bleeding and revascularisation were modelled by logistic regression assessing their relationship with 12-month mortality. Estimates from these models were used to calculate the “attributable fraction”for late mortality associated with each definition. Results: The most liberal definition of myocardial infarction was associated with an attributable risk of 13.7%(95%CI 3.4%to 23.0%). The most stringent definition was associated with an attributable risk of 4.6%(95%CI 0.6%to 8.6%). Restrictive definitions of bleeding such as TIMI(thrombolysis in myocardial infarction) major bleeding are associated with a high odds ratio of risk(6.1, 95%CI 2.1 to 17.7, p=0.001) but low attributable fraction(3.5%, 95%CI 0.9%to 6.8%). Conclusions: Stringent end point definitions may under-represent the clinical significance of adverse outcomes after PCI. Considering both the proportional and absolute risk associated with definitions may be a more useful method for evaluating clinical trial end points. This analysis supports the current definitions of ischaemic events but suggests that more liberal definitions of bleeding events may also be relevant to late mortality.展开更多
Background: The risk of atherothrombosis is a large health care burden worldwide. With its global prevalence, there is a need to understand all the associated risk factors, both old and new, and their interdependencie...Background: The risk of atherothrombosis is a large health care burden worldwide. With its global prevalence, there is a need to understand all the associated risk factors, both old and new, and their interdependencies in the development of this complex disease leading to myocardial infarction, ischemic stroke, and vascular death and, thus, the major cause of mortality throughout the world. Methods: The REACH Registry sought to compile an international data set to extend our knowledge of atherothrombotic risk factors and ischemic events in the outpatient setting. The Registry will recruit approximately 68 000 outpatients in 44 countries across 6 major regions(Latin America, North America, Europe, Asia, the Middle East, and Australia) from >5000 physician outpatient practices. Patients aged ≥45 years with at least 3 atherothrombotic risk factors or documented cerebrovascular, coronary artery, or peripheral arterial disease will be enrolled. Medical history, risk factors, demographic information, and management will be collected at baseline, and clinical events that occur during the follow-up period of up to 2 years in duration will be recorded. Conclusion: The REACH Registry offers an opportunity to provide a better understanding of the prevalence and clinical consequences of atherothrombosis in the outpatient setting in a wide range of patients from different parts of the world.展开更多
文摘BACKGROUND: Dual antiplatelet therapy with clopidogrel plus low-dose aspirin has not been studied in a broad population of patients at high risk for atherothrombotic events. METHODS: We randomly assigned 15,603 patients with either clinically evident cardiovascular disease or multiple risk factors to receive clopidogrel(75 mg per day) plus low-dose aspirin(75 to 162 mg per day) or placebo plus low-dose aspirin and followed them for a median of 28 months. The primary efficacy end point was a composite of myocardial infarction, stroke, or death from cardiovascular causes. RESULTS: The rate of the primary efficacy end point was 6.8 percent with clopidogrel plus aspirin and 7.3 percent with placebo plus aspirin(relative risk, 0.93; 95 percent confidence interval, 0.83 to 1.05; P=0.22). The respective rate of the principal secondary efficacy end point, which included hospitalizations for ischemic events, was 16.7 percent and 17.9 percent(relative risk, 0.92; 95 percent confidence interval, 0.86 to 0.995; P=0.04), and the rate of severe bleeding was 1.7 percent and 1.3 percent(relative risk, 1.25; 95 percent confidence interval, 0.97 to 1.61 percent; P=0.09). The rate of the primary end point among patients with multiple risk factors was 6.6 percent with clopidogrel and 5.5 percent with placebo(relative risk, 1.2; 95 percent confidence interval, 0.91 to 1.59; P=0.20) and the rate of death from cardiovascular causes also was higher with clopidogrel(3.9 percent vs. 2.2 percent, P=0.01). In the subgroup with clinically evident atherothrombosis, the rate was 6.9 percent with clopidogrel and 7.9 percent with placebo(relative risk, 0.88; 95 percent confidence interval, 0.77 to 0.998; P=0.046). CONCLUSIONS: In this trial, there was a suggestion of benefit with clopidogrel treatment in patients with symptomatic atherothrombosis and a suggestion of harm in patients with multiple risk factors. Overall, clopidogrel plus aspirin was not significantly more effective than aspirin alone in reducing the rate of myocardial infarction, stroke, or death from cardiovascular causes.
文摘Objectives: To explore the relative and absolute risks associated with various definitions for myocardial infarction, bleeding and revascularisation within the context of percutaneous coronary intervention(PCI). Methods: The REPLACE-2(randomised evaluation of PCI linking Angiomax to reduced clinical events) database of patients undergoing PCI was used. Various definitions of myocardial infarction, bleeding and revascularisation were modelled by logistic regression assessing their relationship with 12-month mortality. Estimates from these models were used to calculate the “attributable fraction”for late mortality associated with each definition. Results: The most liberal definition of myocardial infarction was associated with an attributable risk of 13.7%(95%CI 3.4%to 23.0%). The most stringent definition was associated with an attributable risk of 4.6%(95%CI 0.6%to 8.6%). Restrictive definitions of bleeding such as TIMI(thrombolysis in myocardial infarction) major bleeding are associated with a high odds ratio of risk(6.1, 95%CI 2.1 to 17.7, p=0.001) but low attributable fraction(3.5%, 95%CI 0.9%to 6.8%). Conclusions: Stringent end point definitions may under-represent the clinical significance of adverse outcomes after PCI. Considering both the proportional and absolute risk associated with definitions may be a more useful method for evaluating clinical trial end points. This analysis supports the current definitions of ischaemic events but suggests that more liberal definitions of bleeding events may also be relevant to late mortality.
文摘Background: The risk of atherothrombosis is a large health care burden worldwide. With its global prevalence, there is a need to understand all the associated risk factors, both old and new, and their interdependencies in the development of this complex disease leading to myocardial infarction, ischemic stroke, and vascular death and, thus, the major cause of mortality throughout the world. Methods: The REACH Registry sought to compile an international data set to extend our knowledge of atherothrombotic risk factors and ischemic events in the outpatient setting. The Registry will recruit approximately 68 000 outpatients in 44 countries across 6 major regions(Latin America, North America, Europe, Asia, the Middle East, and Australia) from >5000 physician outpatient practices. Patients aged ≥45 years with at least 3 atherothrombotic risk factors or documented cerebrovascular, coronary artery, or peripheral arterial disease will be enrolled. Medical history, risk factors, demographic information, and management will be collected at baseline, and clinical events that occur during the follow-up period of up to 2 years in duration will be recorded. Conclusion: The REACH Registry offers an opportunity to provide a better understanding of the prevalence and clinical consequences of atherothrombosis in the outpatient setting in a wide range of patients from different parts of the world.
