Non-Compliance Is the Predominant Cause of Aspirin Resistance.

Classifying patients as resistant to aspirin is an arbitrary designation with up to 60% of patients reported to be aspirin resistant. Our previous publication showed that 16 or 9% of 192 patients with a history of M.I. could be labeled as aspirin resistant and that all of these patients were aspirin resistant because of non-compliance. This report compares the relative frequency of aspirin resistance between known compliant and non-compliance subjects to demonstrate that non-compliance is the predominant cause of aspirin resistance. Platelet prostaglandin agonist (PPA) stimulated light aggregometry was used to measure amount of aspirin induced platelet inhibition and arachidonic acid (AA) stimulated platelet aggregation to classify platelets as either aspirin inhibited or not. After not taking aspirin for 7 days blood for aggregation studies was drawn, off aspirin time point, which was followed by observed ingestion of 365mg of aspirin. Two hours after observed aspirin ingestion aggregation studies were repeated, on aspirin time point. The difference in the slopes of the PPA light aggregation curves on and off aspirin was defined as the net aspirin response. After supposedly refraining from aspirin for 7 days, 45 subjects were judged non-compliant with the protocol and removed from the study. Of the remaining 185 subjects 39 were normals and 146 had a past history of myocardial infarction (MI). There was no difference in net aspirin response between normal and MI subjects. The net aspirin response in known compliant patients was statistically normally distributed. Only 4% of complaint subjects (2 normals and 5 MI) had a net aspirin response of less than one standard deviation which would qualify as a conservative designation of aspirin resistance. Of the 230 enrolled subjects 16 were noncompliant with their daily prescribed aspirin, 45 were non-compliant with the protocol not to take aspirin for 7 days and one patient had NANSAID interference with aspirin’s effect. In total a maximum of 30% of the 230 patients could be classified as aspirin resistant and or non-compliant with 9% aspirin resistant because of non-compliance 18% non-compliant with the protocol and only 3% because of a decreased net aspirin response in known compliant patients. We conclude that:

1. the predominant cause of aspirin resistance is noncompliance;

2. net aspirin response in compliant patients is normally distributed;

3. in compliant patients no difference in net aspirin response is observed between normals and MI patients; and

4. PPA stimulated light aggregometry measured off aspirin and 2 hours after observed aspirin ingestion is a useful technique for measuring net aspirin response.