Some Patients Need More Than Aspirin

Thromboxane Activity at Issue

Previous research had identified three possible explanations for the syndrome known as "aspirin resistance": Platelets might be activated by pathways not blocked by aspirin, some patients may need doses of aspirin higher than the 75 mg to 325 mg currently used, or some patients generate thromboxane Alpha ₂ despite the aspirin doses.

Eikelboom and colleagues evaluated the third of these three options. Working with morning urine samples collected from 5,529 high-risk Canadians who participated in the Heart Outcomes Prevention Evaluation (HOPE) study, the researchers assessed whether failure of aspirin to suppress thromboxane generation increased the risk of cardiovascular events such as myocardial infarction and stroke. For patients who were aged 55 and over and had known coronary artery disease, peripheral vascular disease, or stroke, or diabetes and at least one coronary risk factor, the researchers measured urinary 11-dehydro thromboxane Beta ₂ levels, a stable metabolite of thromboxane Alpha ₂ whose urinary excretion reflects the extent of aspirin-mediated thromboxane inhibition. Aspirin-treated patients who had a confirmed myocardial infarction, stroke, or cardiovascular death after randomization were defined as cases, while other patients were controls.

In patients whose urinary excretion of 11-dehydro thromboxane Beta ₂ was increased, more cardiovascular events occurred. Those patients whose urinary levels fell into the highest quartile had 1.8 times as many cardiovascular events as those in the lowest quartile. These findings support the theory that aspirin resistance is a failure of suppression of thromboxane generation, the third possibility listed above. This raises the prospect that a pharmacogenetic test might someday be used to identify patients prone to aspirin resistance, but no such gene has yet been found.

Pharmacy Today. 2002;8(6):7, 35 © 2002 American Pharmacists Association
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Cite this: Some Patients Need More Than Aspirin - Medscape - Jun 01, 2002.