Antithrombotic Agents. Aspirin

Antithrombotic agents are ultimately aimed at interfering with the process of thrombosis or formation of intravascular clot which involves platelets and fibrin. Antiplatelet agents deter the adherence of platelets to the wall of an injured vessel or to one another. This is an early step in the generation of a thrombus. Anticoagulants prevent the formation and propagation of fibrin which is the essential building block of a thrombus. For cerebral ischemia, a variety of antithrombotic agents have been proven to be of value in the prevention of ischemic stroke after transient ischemic attack, completed infarction, or when certain high-risk conditions are detected such as nonvalvular atrial fibrillation, valvular heart disease, or after acute myocardial infarction. These antithrombotic agents include antiplatelet drugs (aspirin, ticlopidine, dipyridamole, and clopidogrel) and anticoagulants (warfarin). New antiplatelet agents are being tested in a variety of circumstances among patients with cerebrovascular disorders.

Aspirin

Numerous clinical trials have been done comparing aspirin with placebo for the prevention of stroke and death after TIA or minor stroke.The Antiplatelet Trialist Collaboration Group have used meta analyses to combine the results of these various antiplatelet studies in which ASA was the most widely used agent. In their most recent analyses of 17 trials among persons with a past history of stroke or TIA, they reported an odds reduction of 22% for non-fatal stroke, non-fatal MI or vascular death with a 2-year risk of 18% for those treated with antiplatelets and 22% for controls. Few of the individual aspirin studies were directed at the efficacy of aspirin in preventing recurrent stroke after an established stroke. In the meta-analyses among those with a completed stroke, the odds reduction was 16% for non-fatal stroke, non-fatal MI or vascular death. Individual aspirin studies have sometimes failed to find a beneficial effect for women. However, in the meta-analyses similar reductions were found for women and men, young and old, hypertensives and normotensives and diabetics and non-diabetics.

The issue of the dose of aspirin needed to prevent stroke is still controversial. Recommendations range from a low of 30 mg per day to a high of 1300 mg per day. The data for the efficacy of stroke prevention for lower doses is available only from trials involving patients with TIA and minor stroke. Gastrointestinal hemorrhage and other aspirin-related side effects are clearly reduced with the lower doses. The Antiplatelet Trialist’s Collaboration Report cited three trials using doses of 300-325 daily and compared the outcome for major vascular events, including stroke, to the 15 trials using 900-1500 daily. Cheap generic lipitor. The authors concluded “…the studies of 300-325 mg/day appeared to have yielded results that were at least as good as those yielded by 900-1500 mg/day.” However, a review of stroke trials found that the risk reductions were not as great with the low dose aspirin programs compared to the higher dose programs. They stated that this “raised the possibility that 325 mg/day or less of aspirin may not be equally effective as 975 mg/day or more.” The data from aspirin trials suggest that a dose of aspirin as low as 325 mg is better tolerated and might prove as effective as the higher doses of 1000-1300 mg. In 2006, the US Food and Drug Administration revised their recommendations to endorse 50-325 mg of ASA per day as the standard dose to prevent stroke in TIA and stroke survivors.

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