Aspirin dosage and thromboxane synthesis in patients with vascular disease

Study Objective. To determine whether urinary 11-dehydrothromboxane B₂ (d-TXB₂) is a marker of aspirin resistance and define the relationship between aspirin dosage and concentrations of this thromboxane metabolite. Design. Randomized, crossover study. Setting. Two outpatient clinical centers. Patients. Forty-eight patients (mean age 70 yrs) with vascular disease (52% clinical coronary artery disease, 29% cerebrovascular disease, 46% atrial fibrillation). Intervention. Levels of serum thromboxane B₂ and d-TXB₂ were measured after patients were treated initially with aspirin 325 mg/day for 4 weeks, then again after random assignment to receive aspirin 81, 325, or 1300 mg/day for 4 weeks, and then again after resumption of 325 mg/day for 4 weeks. Measurements and Main Results. During treatment with aspirin 325 mg/day, the mean ± SD serum thromboxane B₂ level was 0.9 ± 1.2 ng/ml and median (interquartile range) was 0.4 (0.2-0.9) ng/ml. Mean urinary d-TXB₂ was 16 ± 7.9 ng/mmol creatinine, with a median of 15 (9.9-23) ng/mmol creatinine with aspirin 325 mg/day. After 4 weeks of aspirin 81 mg/day, levels of serum thromboxane B₂ (p<0.01) and urinary d-TXB₂ (p=0.04) were both significantly higher compared with aspirin 325 mg/day; for urinary d-TXB₂, the median increase was 3.0 ng/mmol creatinine. After 4 weeks of treatment with aspirin 1300 mg/day, levels of serum thromboxane B₂ (p<0.01) and urinary d-TXB₂ (p<0.01) were both significantly lower compared with aspirin 325 mg/day; the median decrease in urinary d-TXB₂ was 4.4 ng/mmol creatinine. Conclusion. Different aspirin dosages significantly affect serum and urinary markers of thromboxane synthesis.