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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

View larger version (19K): [in a new window]   Figure 1 The role of cyclooxygenase-1 in thromboxane (TX) synthesis and the inhibitory action of aspirin. PGH2 = prostaglandin H2.

View larger version (16K): [in a new window]   Figure 2 A sigmoid relationship between serum thromboxane (TX) (ng/ml) on the y-axis and platelet TX (ng/ml) (TX generated when exogenous arachidonic acid is added to platelets) on the x-axis is evident (n = 45, R2 = 0.67). The point of inflection of the graph occurs at a serum TX level of 2.2 ng/ml.

View larger version (14K): [in a new window]   Figure 3 Platelet thromboxane generation (ng/ml) on the x-axis correlates with arachidonic acid-induced platelet aggregation (%) on the y-axis (n = 45, R2 = 0.9). Both variables depend on cyclooxygenase (COX) activity. Two distinct populations are evident reflecting absence and presence of active platelet COX.

View larger version (11K): [in a new window]   Figure 4 The relationship between serum thromboxane (TX) and arachidonic acid-induced platelet aggregation (AA Agg). At thromboxane levels above 2 ng/ml the population divides into two groups, one with full inhibition and the other with no inhibition of arachidonic acid-induced platelet aggregation.

View larger version (13K): [in a new window]   Figure 5 Probability of an incomplete response to aspirin (serum thromboxane >2.2 ng/ml) on the y-axis is related to patient weight on the x-axis and stratified by patient age. Weight and age are significant independent predictors of aspirin response on multivariate analysis (p = 0.025 and 0.0086, respectively).