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Aspirin Dosage and Thromboxane Synthesis in Patients with Vascular Disease
Author(s) -
Hart Robert G.,
Leonard Anne D.,
Talbert Robert L.,
Pearce Lesly A.,
Cornell Elaine,
Bovill Edwin,
Feinberg William M.
Publication year - 2003
Publication title -
pharmacotherapy: the journal of human pharmacology and drug therapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.227
H-Index - 109
eISSN - 1875-9114
pISSN - 0277-0008
DOI - 10.1592/phco.23.5.579.32206
Subject(s) - aspirin , medicine , thromboxane b2 , creatinine , thromboxane , urinary system , crossover study , interquartile range , gastroenterology , urology , platelet , pathology , alternative medicine , placebo
Study Objective . To determine whether urinary 11‐dehydrothromboxane B 2 (d‐TXB 2 ) 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 B 2 and d‐TXB 2 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 B 2 level was 0.9 ± 1.2 ng/ml and median (interquartile range) was 0.4 (0.2–0.9) ng/ml. Mean urinary d‐TXB 2 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 B 2 (p<0.01) and urinary d‐TXB 2 (p=0.04) were both significantly higher compared with aspirin 325 mg/day; for urinary d‐TXB 2 , the median increase was 3.0 ng/mmol creatinine. After 4 weeks of treatment with aspirin 1300 mg/day, levels of serum thromboxane B 2 (p<0.01) and urinary d‐TXB 2 (p<0.01) were both significantly lower compared with aspirin 325 mg/day; the median decrease in urinary d‐TXB 2 was 4.4 ng/mmol creatinine. Conclusion . Different aspirin dosages significantly affect serum and urinary markers of thromboxane synthesis.