Tuesday, March 31, 2009
AF atrial fibrillation
Original Article
Published at www.nejm.org March 31, 2009 (10.1056/NEJMoa0901301)
Effect of Clopidogrel Added to Aspirin in Patients with Atrial Fibrillation
The ACTIVE Investigators
This Article
- Abstract
- PDF
Tools and Services
- Add to Personal Archive
- Add to Citation Manager
- Notify a Friend
- E-mail When Cited
More Information
ABSTRACT
Background Vitamin K antagonists reduce the risk of stroke in patients with atrial fibrillation but are considered unsuitable in many patients, who usually receive aspirin instead. We investigated the hypothesis that the addition of clopidogrel to aspirin would reduce the risk of vascular events in patients with atrial fibrillation.
Methods A total of 7554 patients with atrial fibrillation who had an increased risk of stroke and for whom vitamin K–antagonist therapy was unsuitable were randomly assigned to receive clopidogrel (75 mg) or placebo, once daily, in addition to aspirin. The primary outcome was the composite of stroke, myocardial infarction, non–central nervous system systemic embolism, or death from vascular causes.
Results At a median of 3.6 years of follow-up, major vascular events had occurred in 832 patients receiving clopidogrel (6.8% per year) and in 924 patients receiving placebo (7.6% per year) (relative risk with clopidogrel, 0.89; 95% confidence interval [CI], 0.81 to 0.98; P=0.01). The difference was primarily due to a reduction in the rate of stroke with clopidogrel. Stroke occurred in 296 patients receiving clopidogrel (2.4% per year) and 408 patients receiving placebo (3.3% per year) (relative risk, 0.72; 95% CI, 0.62 to 0.83; P<0.001). Myocardial infarction occurred in 90 patients receiving clopidogrel (0.7% per year) and in 115 receiving placebo (0.9% per year) (relative risk, 0.78; 95% CI, 0.59 to 1.03; P=0.08). Major bleeding occurred in 251 patients receiving clopidogrel (2.0% per year) and in 162 patients receiving placebo (1.3% per year) (relative risk, 1.57; 95% CI, 1.29 to 1.92; P<0.001).
Conclusions In patients with atrial fibrillation for whom vitamin K–antagonist therapy was unsuitable, the addition of clopidogrel to aspirin reduced the risk of major vascular events, especially stroke, and increased the risk of major hemorrhage. (ClinicalTrials.gov number, NCT00243178 [ClinicalTrials.gov] .)
Atrial fibrillation is a common cardiac arrhythmia that increases the risk of stroke by a factor of five.1 Adjusted-dose vitamin K antagonists and antiplatelet agents reduce the risk of stroke by 64% and 22%, respectively.2 As compared with aspirin, vitamin K antagonists reduce the risk of stroke by 38% but more than double the risk of intracranial hemorrhage and increase the risk of major extracranial hemorrhage by 70%. They do not reduce mortality from any cause or from vascular causes.2,3 On the basis of these data, vitamin K antagonists are recommended for patients at higher risk for stroke, and aspirin for patients at lower risk.4,5
Vitamin K antagonists have a narrow window for a therapeutic benefit and require regular monitoring of the international normalized ratio (INR).6 Several surveys in North America and Europe indicate that only about 50% of patients with atrial fibrillation who are at increased risk for stroke receive vitamin K antagonists.7,8,9,10 Patients may not be treated with a vitamin K antagonist for any number of reasons, including concern about interactions with other drugs, the increased risk of hemorrhage, inadequate compliance with INR monitoring, and a desire by the patient to avoid vitamin K–antagonist therapy. Most of these patients are treated with aspirin.
The benefit of combining clopidogrel with aspirin has been proven in patients with acute coronary syndromes.11 The Atrial Fibrillation Clopidogrel Trial with Irbesartan for Prevention of Vascular Events (ACTIVE) was initiated to evaluate the role of clopidogrel plus aspirin for the prevention of stroke and other vascular events in patients with atrial fibrillation. ACTIVE W, which has previously been reported,12 compared clopidogrel plus aspirin with a vitamin K antagonist. ACTIVE A, reported here, compared clopidogrel plus aspirin with aspirin alone in patients with atrial fibrillation who were at increased risk for stroke and for whom therapy with a vitamin K antagonist was considered unsuitable.
Published at www.nejm.org March 31, 2009 (10.1056/NEJMoa0901301)
Effect of Clopidogrel Added to Aspirin in Patients with Atrial Fibrillation
The ACTIVE Investigators
This Article
- Abstract
Tools and Services
- Add to Personal Archive
- Add to Citation Manager
- Notify a Friend
- E-mail When Cited
More Information
ABSTRACT
Background Vitamin K antagonists reduce the risk of stroke in patients with atrial fibrillation but are considered unsuitable in many patients, who usually receive aspirin instead. We investigated the hypothesis that the addition of clopidogrel to aspirin would reduce the risk of vascular events in patients with atrial fibrillation.
Methods A total of 7554 patients with atrial fibrillation who had an increased risk of stroke and for whom vitamin K–antagonist therapy was unsuitable were randomly assigned to receive clopidogrel (75 mg) or placebo, once daily, in addition to aspirin. The primary outcome was the composite of stroke, myocardial infarction, non–central nervous system systemic embolism, or death from vascular causes.
Results At a median of 3.6 years of follow-up, major vascular events had occurred in 832 patients receiving clopidogrel (6.8% per year) and in 924 patients receiving placebo (7.6% per year) (relative risk with clopidogrel, 0.89; 95% confidence interval [CI], 0.81 to 0.98; P=0.01). The difference was primarily due to a reduction in the rate of stroke with clopidogrel. Stroke occurred in 296 patients receiving clopidogrel (2.4% per year) and 408 patients receiving placebo (3.3% per year) (relative risk, 0.72; 95% CI, 0.62 to 0.83; P<0.001). Myocardial infarction occurred in 90 patients receiving clopidogrel (0.7% per year) and in 115 receiving placebo (0.9% per year) (relative risk, 0.78; 95% CI, 0.59 to 1.03; P=0.08). Major bleeding occurred in 251 patients receiving clopidogrel (2.0% per year) and in 162 patients receiving placebo (1.3% per year) (relative risk, 1.57; 95% CI, 1.29 to 1.92; P<0.001).
Conclusions In patients with atrial fibrillation for whom vitamin K–antagonist therapy was unsuitable, the addition of clopidogrel to aspirin reduced the risk of major vascular events, especially stroke, and increased the risk of major hemorrhage. (ClinicalTrials.gov number, NCT00243178 [ClinicalTrials.gov] .)
Atrial fibrillation is a common cardiac arrhythmia that increases the risk of stroke by a factor of five.1 Adjusted-dose vitamin K antagonists and antiplatelet agents reduce the risk of stroke by 64% and 22%, respectively.2 As compared with aspirin, vitamin K antagonists reduce the risk of stroke by 38% but more than double the risk of intracranial hemorrhage and increase the risk of major extracranial hemorrhage by 70%. They do not reduce mortality from any cause or from vascular causes.2,3 On the basis of these data, vitamin K antagonists are recommended for patients at higher risk for stroke, and aspirin for patients at lower risk.4,5
Vitamin K antagonists have a narrow window for a therapeutic benefit and require regular monitoring of the international normalized ratio (INR).6 Several surveys in North America and Europe indicate that only about 50% of patients with atrial fibrillation who are at increased risk for stroke receive vitamin K antagonists.7,8,9,10 Patients may not be treated with a vitamin K antagonist for any number of reasons, including concern about interactions with other drugs, the increased risk of hemorrhage, inadequate compliance with INR monitoring, and a desire by the patient to avoid vitamin K–antagonist therapy. Most of these patients are treated with aspirin.
The benefit of combining clopidogrel with aspirin has been proven in patients with acute coronary syndromes.11 The Atrial Fibrillation Clopidogrel Trial with Irbesartan for Prevention of Vascular Events (ACTIVE) was initiated to evaluate the role of clopidogrel plus aspirin for the prevention of stroke and other vascular events in patients with atrial fibrillation. ACTIVE W, which has previously been reported,12 compared clopidogrel plus aspirin with a vitamin K antagonist. ACTIVE A, reported here, compared clopidogrel plus aspirin with aspirin alone in patients with atrial fibrillation who were at increased risk for stroke and for whom therapy with a vitamin K antagonist was considered unsuitable.
# posted by roodbont @ 1:08 PM 
