title: Aspirin-resistant thromboxane biosynthesis and the risk of myocardial infarction, stroke, or cardiovascular death in patients at high risk for cardiovascular events.
abstract: 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.
  
  
  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 B2 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 B2, 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 B2 predict the future risk of myocardial infarction or cardiovascular death. These findings raise the possibility that elevated urinary 11-dehydro thromboxane B2 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.
authors.affiliation: Department of Medicine, University of Western Australia, Thrombosis and Haemophilia Unit, Royal Perth Hospital, Perth, Australia. john.eikelboom@health.wa.gov.au
authors.forename: John W
authors.initials: JW
authors.lastname: Eikelboom
authors.forename: Jack
authors.initials: J
authors.lastname: Hirsh
authors.forename: Jeffrey I
authors.initials: JI
authors.lastname: Weitz
authors.forename: Marilyn
authors.initials: M
authors.lastname: Johnston
authors.forename: Qilong
authors.initials: Q
authors.lastname: Yi
authors.forename: Salim
authors.initials: S
authors.lastname: Yusuf
mesh_terms: D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D001241:Aspirin / Q000627:therapeutic use*; D002170:Canada / Q000453:epidemiology; D002318:Cardiovascular Diseases / Q000188:drug therapy* / Q000453:epidemiology / Q000378:metabolism; D016022:Case-Control Studies; D015331:Cohort Studies; D015897:Comorbidity; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use; D016757:Death, Sudden, Cardiac / Q000453:epidemiology / Q000517:prevention & control*; D003710:Demography; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D009203:Myocardial Infarction / Q000453:epidemiology / Q000517:prevention & control*; D016017:Odds Ratio; D016032:Randomized Controlled Trials as Topic; D018570:Risk Assessment; D012307:Risk Factors; D055502:Secondary Prevention; D020521:Stroke / Q000453:epidemiology / Q000517:prevention & control*; D013929:Thromboxane B2 / Q000031:analogs & derivatives* / Q000652:urine; D013931:Thromboxanes / Q000096:biosynthesis* / Q000652:urine; D014810:Vitamin E / Q000627:therapeutic use
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D016861:Cyclooxygenase Inhibitors; D013931:Thromboxanes; D014810:Vitamin E; D013929:Thromboxane B2; C049235:11-dehydro-thromboxane B2; D001241:Aspirin