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The WATCHMAN Left Atrial Appendage Closure Device for Atrial Fibrillation
Published on: February 28, 2012
Effect of clopidogrel added to aspirin in patients with atrial fibrillation
Insights
Adding clopidogrel to aspirin therapy for atrial fibrillation patients not suitable for vitamin K antagonists significantly reduced major vascular events, particularly stroke. However, this combination also increased the risk of major hemorrhage.
Area of Science:
- Cardiology
- Vascular Medicine
- Pharmacology
Background:
- Atrial fibrillation (AF) patients at risk of stroke often cannot use vitamin K antagonists (VKAs).
- Aspirin is a common alternative, but its efficacy in preventing vascular events in AF is limited.
- Investigating combination therapy for AF patients unsuitable for VKAs is crucial.
Purpose of the Study:
- To evaluate if adding clopidogrel to aspirin reduces vascular events in AF patients.
- To assess the safety profile of clopidogrel plus aspirin in this patient population.
Main Methods:
- A randomized trial involving 7554 AF patients at increased stroke risk, unsuitable for VKAs.
- Patients received daily clopidogrel (75 mg) or placebo, in addition to aspirin.
- Primary outcome: composite of stroke, myocardial infarction, systemic embolism, or vascular death.
Main Results:
- Clopidogrel plus aspirin reduced major vascular events by 11% (relative risk, 0.89; P=0.01).
- Stroke incidence significantly decreased with clopidogrel (2.4% vs. 3.3% per year; P<0.001).
- Major hemorrhage risk increased by 57% with clopidogrel (2.0% vs. 1.3% per year; P<0.001).
Conclusions:
- For AF patients unsuitable for VKAs, clopidogrel plus aspirin reduces major vascular events, primarily stroke.
- The combination therapy leads to a significant increase in major hemorrhage risk.
- Risk-benefit assessment is essential when considering clopidogrel addition to aspirin in AF management.
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, NCT00249873.)
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