Aspirin resistance

• long term aspirin use attenuates the risks of myocardial infarction, stroke, and vascular related deaths in patients with cardiovascular disease
  • major controversy about aspirin therapy is why particular patients do not benefit from such therapy and how they might be identified
  • been suggested that some patients require a higher dose of aspirin than is normally recommended to achieve the expected antiplatelet effect-for example, inhibition of platelet function or inhibition of platelet thromboxane A2 synthesis
    • unclear whether these patients simply receive too low an aspirin dose, are not compliant, have differing abilities to absorb aspirin, or have an underlying genetic disposition that renders aspirin ineffective
      • these patients have been labelled aspirin "resistant" that is, their platelets are not affected in the same way or are affected differently from the platelets of those who seem to benefit from aspirin therapy (aspirin "sensitive" patients with no subsequent adverse cardiovascular event) (1) - term "aspirin resistance" has various synonyms, including "aspirin nonresponsiveness","aspirin treatment failure",and "inadequate aspirin efficacy", but has also been sometimes defined as "biochemical or laboratory aspirin resistance" (2)
      • estimates of the prevalence of aspirin resistance vary widely (5.5% to 60%), reflecting the diversity of various laboratory assays and confounding from the broad range of disease states investigated
      • it has been suggested that possible causes of aspirin resistance might be divided into 2 main groups (2):

Those related to the COX-1 pathway of thromboxane A2 production

causes of aspirin resistanc associated with non-COX-1 related causes

• a systematic review investigated aspirin "resistance" and risk of cardiovascular morbidity (1)
  • 20 studies totalling 2930 patients with cardiovascular disease were identified. Most studies used aspirin regimens, ranging from 75-325 mg daily, and six studies included adjunct antiplatelet therapy
    • overall, 810 patients (28%) were classified as aspirin resistant
      • a cardiovascular related event occurred in 41% of patients of aspirin resistant patients (odds ratio 3.85, 95% confidence interval 3.08 to 4.80), death in 5.7% (5.99, 2.28 to 15.72), and an acute coronary syndrome in 39.4% (4.06, 2.96 to 5.56)
      • aspirin resistant patients did not benefit from other antiplatelet treatment
  • study authors concluded that patients who are resistant to aspirin are at a greater risk of clinically important cardiovascular morbidity long term than patients who are sensitive to aspirin

• note though that despite the emergence of "aspirin resistance" as a clinical phenomenon, aspirin still remains the most commonly prescribed drug for prevention of atherothrombotic events (2)
  • due not only to its potent inhibition of the thromboxane A2 pathway, which is undoubtedly crucial for platelet activation and aggregation, but also because of a number of pleiotropic effects ( e.g. suppression of acute phase reactants and subclinical inflammation, stimulation of NO synthesis, immunomodulatory effect on activated macrophages and lymphocytes)

Reference:

• (1) Brister SJ et al. Aspirin 'resistance' and risk of cardiovascular morbidity: systematic review and meta-analysis. BMJ. 2008 Jan 26;336(7637):195-8.
• (2) Gasparyan AY et al. The Role of Aspirin in Cardiovascular Prevention: Implications of Aspirin Resistance Journal of the American College of Cardiology 2008; 51 (19):1829-1843.