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Many questions remain surrounding aspirin resistance
Newer antiplatelet agents may offer some hope for aspirin-resistant patients, but uncertainty remains regarding their clinical application.
While aspirin remains an important tool for helping to manage risks of cardiovascular and thromboembolic events in many fields of medicine, the medical community are increasingly recognizing that some patients may be resistant to its beneficial effects.
And despite a strong understanding of how aspirin acts on platelets, the clinical implications of aspirin resistance remain far from clear, according to a review article by Amgad N. Makaryus, MD, published in the journal Clinical Cardiology.
“There is no consensus on the ideal technique for the assessment of the presence of aspirin resistance and therefore no agreement about a standardized definition,” Makaryus said in the review. “This lack of a uniform definition has led to a lack of appreciation of the true clinical significance of aspirin resistance,” he said.
Drafting an accurate definition
Numerous attempts to define aspirin resistance have used clinical measures and laboratory studies, including platelet function and platelet-aggregation. But such studies can be difficult to perform and can yield variable results.
Recently, urinary 11-dehydrothromboxane B2 levels have been used as a marker for thromboxane formation suppression, which reflects both platelet and nonplatelet sources, making it less specific. However, “All of these techniques identify a decreased response to aspirin that falls within a wide range of variation from 5% to 60%,” Makaryus said.
“Aspirin resistance likely stems from a variable response to aspirin in a diversity of pathways that all have the same effect of altering platelet aggregation,” he said, noting some studies have suggested increased reactivity to inducers of platelet activation, including collagen and platelet activating factor (PAF). “Along with this increased reactivity to induction of aggregation usually comes decreased response to the anti-aggregatory effects of substances such as prostaglandin I2,” he said.
In addition to the questions surrounding the mechanisms leading to aspirin resistance, few long-term clinical studies have looked at its clinical significance. There are also no specific guidelines for treating aspirin-resistant patients, the review noted.
New options
Newer antiplatelet agents, such as clopidogrel (Plavix, Bristol-Myers Squibb/Sanofi Pharm.), may offer some hope. But, again, there remains uncertainty regarding how to apply such agents clinically. “[It] has been questioned whether patients who are aspirin resistant may benefit from either substitution of these new agents for aspirin or the combination of these new agents with aspirin,” Makaryus said.
He noted that studies show clopidogrel has a significant clinical benefit when used alone and when combined with aspirin compared to aspirin alone. “What is not clear, however, is whether this benefit is related to the compensation for aspirin resistance ... and whether adding clopidogrel to a patient with aspirin resistance will help overcome the observed adverse outcomes,” he said, adding that ongoing trials may provide further insight.
For more information:
- Makaryus AN. Aspirin resistance: an emerging, often overlooked factor in the management of patients with coronary artery disease. Clin Cardiol. 2006;29:144-148.