Frequency of aspirin resistance in patients with chronic ischemic heart disease in Çukurova region and treatment change effects on the platelet functions and prognosis

Purpose: Aspirin is the cornerstone of antiplatelet therapy in cardiovascular medicine today. However the antiplatelet effect of aspirin is not uniform in all patients. Previously published work has demonstrated aspirin resistance in 0,4% to 83,3% of aspirin-treated patients. The aim of this study was to investigate the frequency of aspirin resistance who were taking 100 mg of aspirin and the effect of aspirin 300 mg/day or combined therapy with aspirin 100 mg/day and clopidogrel 75 mg/day on platelet function and morbidity in patients with stable coronary artery disease whose platelet function was not adequately inhibited by aspirin 100 mg/day.Material and Methods: 168 patients (115 males and 53 females, mean age 60.1 ± 8.4 years) with stable coronary artery disease who are using aspirin 100 mg/day were included the study. All patients are followed by Cardiology Department of Çukurova University Faculty of Medicine. Modified thromboelastogram was used to determine aspirin responsiveness. Aspirin resistance definitions included <50% arachidonic acid induced whole blood trombosit aggregation inhibition by TEG. Aspirin nonresponders were randomized to aspirin 300 mg/day or aspirin 100 mg/day plus clopidogrel 75 mg/day and platelet aggregation inhibition levels were measured again. The patients were followed up 464±264 (200-728) days.Results: We found aspirin resistance in 27 (16.1%) patients. Platelet aggregation inhibition levels in patients using 100 mg aspirin is found to be significantly increased with increasing dosage of aspirin to the 300 mg or adding 75 mg clopidogrel to the 100 mg aspirin (p=0.008), but resistance is still to be observed in patients 16 and 11 respectively. This difference between the two groups was statistically insignificant (p=0.508). In comparison to patients, using 100 mg aspirin plus 75 mg clopidogrel platelet aggregation inhibition levels are found to be much more higher in patients using 300 mg aspirin but this difference was not statistically significant (p= 0.205). Only fibrinogen levels and pulse pressures are found to be independent indicator in prediction of aspirin resistance and platelet aggregation inhibition. Cut off values of 50 mmHg for pulse pressure and 400 mg/dl for mean fibrinogen are predicted to be aspirin resistance in a sensitivity of 88.9%, 74% and spesifity of 64.4%, 68% respectively. 27 patients who are resistant to 100 mg aspirin therapy were randomized to 300 mg aspirin or 100 mg aspirin + 75 mg clopidogrel. After changing treatment modality 20 patients with adequate TAI levels and 7 patients without adequate platelet aggregation inhibition levels were found and these patients are compared for morbidity. Morbidity is found significantly higher in patients with aspirin resistance (TAI <50%) (p=0.045).Conclusions: In conclusion, aspirin 100 mg/day does not inhibit platelet function adequately 16.1% of patients with coronary artery disease. Increasing the aspirin dose to 300 mg/day or adding 75 mg/day clopidogrel to 100 mg aspirin can provide adequate platelet inhibition in a significant number of those patients with impaired responses to low-dose aspirin. Patients who are resistant to aspirin were at a greater risk of cardiovascular morbidity.