Aspirin-Resistant Thromboxane Biosynthesis and the Risk of Myocardial Infarction, Stroke, or Cardiovascular Death in Patients at High Risk for Cardiovascular Events

• Published in: Circulation (New York, N.Y.) Vol. 105; no. 14; pp. 1650 - 1655
• Main Authors: Eikelboom, John W., Hirsh, Jack, Weitz, Jeffrey I., Johnston, Marilyn, Yi, Qilong, Yusuf, Salim
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 09.04.2002; American Heart Association, Inc
• Subjects: Aged; Angiotensin-Converting Enzyme Inhibitors - therapeutic use; Aspirin - therapeutic use; Biological and medical sciences; Blood. Blood coagulation. Reticuloendothelial system; Canada - epidemiology; Cardiovascular Diseases - drug therapy; Cardiovascular Diseases - epidemiology; Cardiovascular Diseases - metabolism; Case-Control Studies; Cohort Studies; Comorbidity; Cyclooxygenase Inhibitors - therapeutic use; Death, Sudden, Cardiac - epidemiology; Death, Sudden, Cardiac - prevention & control; Demography; Female; Follow-Up Studies; Humans; Male; Medical sciences; Myocardial Infarction - epidemiology; Myocardial Infarction - prevention & control; Odds Ratio; Pharmacology. Drug treatments; Randomized Controlled Trials as Topic; Risk Assessment; Risk Factors; Secondary Prevention; Stroke - epidemiology; Stroke - prevention & control; Thromboxane B2 - analogs & derivatives; Thromboxane B2 - urine; Thromboxanes - biosynthesis; Thromboxanes - urine; Vitamin E - therapeutic use; Canada; Human; Nervous system diseases; Stroke; Treatment resistance; Prognosis; Infarct; Arachidonic acid derivatives; Cardiovascular disease; Acetylsalicylic acid; Coronary heart disease; Myocardial disease; Antiplatelet agent; Cerebral disorder; Vascular disease; Chemotherapy; Treatment; Central nervous system disease; Myocardium; Salicylates; Thromboxane; Cerebrovascular disease
• ISSN: 0009-7322; 1524-4539; 1524-4539
• DOI: 10.1161/01.CIR.0000013777.21160.07

Background — We studied whether aspirin resistance, defined as failure of suppression of thromboxane generation, increases the risk of cardiovascular events in a high-risk population. Methods and Results — Baseline urine samples were obtained from 5529 Canadian patients enrolled in the Heart Outcomes Prevention Evaluation (HOPE) Study. Using a nested case-control design, we measured urinary 11-dehydro thromboxane B 2 levels, a marker of in vivo thromboxane generation, in 488 cases treated with aspirin who had myocardial infarction, stroke, or cardiovascular death during 5 years of follow-up and in 488 sex- and age-matched control subjects also receiving aspirin who did not have an event. After adjustment for baseline differences, the odds for the composite outcome of myocardial infarction, stroke, or cardiovascular death increased with each increasing quartile of 11-dehydro thromboxane B 2 , with patients in the upper quartile having a 1.8-times-higher risk than those in the lower quartile (OR, 1.8; 95% CI, 1.2 to 2.7; P =0.009). Those in the upper quartile had a 2-times-higher risk of myocardial infarction (OR, 2.0; 95% CI, 1.2 to 3.4; P =0.006) and a 3.5-times-higher risk of cardiovascular death (OR, 3.5; 95% CI, 1.7 to 7.4; P <0.001) than those in the lower quartile. Conclusions — In aspirin-treated patients, urinary concentrations of 11-dehydro thromboxane B 2 predict the future risk of myocardial infarction or cardiovascular death. These findings raise the possibility that elevated urinary 11-dehydro thromboxane B 2 levels identify patients who are relatively resistant to aspirin and who may benefit from additional antiplatelet therapies or treatments that more effectively block in vivo thromboxane production or activity.