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J Am Coll Cardiol, 2005; 46:1258-1263, doi:10.1016/j.jacc.2005.06.058
© 2005 by the American College of Cardiology Foundation
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CLINICAL RESEARCH: CHRONIC CORONARY DISEASE

Platelet Response to Low-Dose Enteric-Coated Aspirin in Patients With Stable Cardiovascular Disease

Andrew O. Maree, MSc, MD*, Ronan J. Curtin, MSc, MD*, Michelle Dooley, BSc*, Ronan M. Conroy, BA, DSc{dagger}, Peter Crean, MD, FRCPI{ddagger}, Dermot Cox, BSc, PhD*,* and Desmond J. Fitzgerald, MD, FRCPI§

* Department of Clinical Pharmacology, Royal College of Surgeons in Ireland, Dublin, Ireland
{dagger} Department of Epidemiology and Public Health, Royal College of Surgeons in Ireland, Dublin, Ireland
{ddagger} Department of Cardiology, Beaumont Hospital, Dublin, Ireland
§ Department of Cardiology, St. James’s Hospital, Dublin, Ireland

Manuscript received February 11, 2005; revised manuscript received June 7, 2005, accepted June 13, 2005.

* Reprint requests and correspondence: Dr. Dermot Cox, Department of Clinical Pharmacology, The Royal College of Surgeons in Ireland, 123 St. Stephen’s Green, Dublin 2, Ireland. (Email: dcox{at}rcsi.ie).

OBJECTIVES: We investigated whether use of low-dose enteric-coated (EC) aspirin for secondary prevention of cardiovascular events has sufficient bioavailability to achieve complete platelet cyclooxygenase (COX) inhibition in all individuals.

BACKGROUND: Aspirin reduces cardiovascular morbidity and mortality in patients with pre-existing vascular disease; however, there is variability in the way individuals respond. Persistent normal platelet function despite therapy, referred to as "aspirin resistance," is associated with an increased risk of major cardiovascular events.

METHODS: We studied 131 stable cardiovascular patients between March and September 2002 who were taking 75 mg EC aspirin. Serum thromboxane (TX) B2 levels were assayed as a measure of COX activity. Mean arachidonic acid (AA)-induced platelet aggregation ≥20% was deemed evidence of persistent platelet activity and an incomplete aspirin response.

RESULTS: Patients of median age 63 years (61% men) were enrolled. Forty-four percent of patients had elevated serum TX B2 levels (>2.2 ng/ml). Arachidonic acid-induced platelet aggregation occurred more frequently in these patients (21% vs. 3%; p = 0.004). In all cases addition of exogenous aspirin during the assay abolished platelet aggregation. Patient weight and age were significant independent predictors of an incomplete response to EC aspirin (p = 0.025 and p < 0.001, respectively). These patients were also more likely to have a history of myocardial infarction (MI) (p = 0.038).

CONCLUSIONS: Many patients who are prescribed low-dose EC aspirin for secondary prevention of cardiovascular events have persistent uninhibited platelet COX activity. Younger and heavier patients and those with a previous MI are most likely to have an inadequate response to treatment.

Abbreviations and Acronyms
  AA = arachidonic acid
  COX = cyclooxygenase
  EC = enteric-coated
  MI = myocardial infarction
  NSAIDs = non-steroidal anti-inflammatory drugs
  TX = thromboxane




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