Aspirin Dosage and Thromboxane Synthesis in Patients with Vascular Disease

Authors


Clinical Pharmacy Program, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900; e-mail: talbert@uthscsa.edu.

Abstract

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.

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