Aspirin resistance : position paper of the Working Group on Aspirin Resistance

Aspirin irreversibly acetylates serine 529 of cyclooxygenase (COX)-1, resulting in inhibition of thromboxane A2 generation by platelets and prostacyclin by endothelial cells [1]. Because platelets lack the synthetic machinery to generate significant amounts of new COX, aspirin-induced COX-1 inhibition lasts for the lifetime of the platelet. In contrast, endothelial cells retain their capacity to generate new COX and recover normal function shortly after exposure to aspirin. Platelets have an increasingly well-defined, critical role in the acute thrombotic events associated with arterial diseases. Antiplatelet drugs have therefore assumed a major role in the therapy of these disorders [1]. Aspirin reduces the odds of an arterial thrombotic event in high-risk patients by 25% [1]. However, 10%–20% of patients with an arterial thrombotic event who are treated with aspirin have a recurrent arterial thrombotic event during long-term followup [1]. In some studies, the occurrence of an arterial thrombotic event despite aspirin therapyhas been termed aspirin resistance .However, because arterial thrombosis is multifactorial, an arterial thrombotic event in a patient may reflect treatment failure rather than resistance to aspirin. Furthermore, patient non-compliance with aspirin administration is a confounding problem. There is a well-documented variability between patients (and normal volunteers) with regard to laboratory test responses to aspirin [2–7]. This variability in laboratory test response has also been termed aspirin resistance (Table 1). Possible mechanisms of aspirin resistance are listed in Table 2. There is an evidence that major adverse clinical events (MACE) in the settings of acute coronary syndromes, stroke/ transient ischemic attacks, and peripheral arterial disease can be predicted by some tests of aspirin resistance (Table 1) [2–7]. However, in most of these studies [2–7] the number of MACE was low, and additional studies are therefore needed