Abstract TP412: Predicting Pharmacokinetic versus Pharmacodynamic Aspirin Resistance in Patients

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Abstract

20%-40% of patients being treated with aspirin for secondary prophylaxis of stroke or myocardial infarction may derive no antiplatelet effects. Early identification of patients as pharmacokinetically or pharmacodynamically resistant to aspirin has the potential to become an invaluable clinical tool, reducing delays to optimal treatment, cardiovascular events, and healthcare costs. This study tested the capability of an assay that was previously developed in healthy volunteers, to differentiate between these two types of resistance in patients.

Patients who needed aspirin treatment in the course of normal medical care were included. Dose escalation of chewable aspirin from 81 mg, to 162 mg, to a maximum 325 mg daily occurred every 10-14 days based on the results of whole blood impedance aggregation testing to the agonists, collagen (1 ug/mL, 5 ug/mL) and arachidonate (0.5 mM). The in vitro test was conducted in triplicate by performing the same aggregometry test on blood samples spiked to a concentration of 10 uM of aspirin in 0.05% dimethyl sulfoxide. Resistance was defined as a response to collagen 1 ug/mL >10 ohms, and/or response to arachidonate >6 ohms, and/or the ratio of collagen 1 to 5 ug/mL >0.5. Patients were excluded if they had any disorders affecting platelet function, an abnormal CBC, alcohol use within 24 hours of a test, NSAID use, or had any conditions that would affect absorption.

Of the 36 patients included who were compliant with their 81 mg aspirin regimen based on pill count, 16 were found to be resistant to 81 mg of aspirin. Nine of these patients were predicted to stay resistant despite dose increase. Once tested at higher doses, ten actually remained resistant. Seven of the 16 patients were predicted to become sensitive to a higher dose of aspirin while six actually did. No statistical difference was found between predicted aspirin response and actual aspirin response (p=0.61). Sensitivity was 83% and specificity was 80%.

In conclusion, results are promising and indicate that it is possible to predict, with reasonable accuracy, if a patient will have an adequate platelet response to aspirin or if the patient will never respond to aspirin therapy necessitating an alternative antiplatelet regimen. Larger, multi-site studies are inevitably needed.

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