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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, Peter Crean, MD, FRCPI, Dermot Cox, BSc, PhD^_*,_* and Desmond J. Fitzgerald, MD, FRCPI

^_* Department of Clinical Pharmacology, Royal College of Surgeons in Ireland, Dublin, Ireland
Department of Epidemiology and Public Health, Royal College of Surgeons in Ireland, Dublin, Ireland
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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