April 9, 2002Circulation1,058 citationsOpen Access
View Full PaperAspirin-Resistant Thromboxane Biosynthesis and the Risk of Myocardial Infarction, Stroke, or Cardiovascular Death in Patients at High Risk for Cardiovascular Events
Key Result
Aspirin-treated patients in the upper quartile of urinary 11-dehydro thromboxane B2 had a higher risk of MI, stroke, or CV death than those in the lower quartile (OR 1.8; 95% CI 1.2-2.7; P=0.009).
Study Design
Type
Case-Control (n=976)
Structured PICO
Does elevated urinary 11-dehydro thromboxane B2 (aspirin resistance) increase the risk of myocardial infarction, stroke, or cardiovascular death in high-risk patients treated with aspirin?
P
Population
976 Canadian patients (488 cases, 488 sex- and age-matched controls) treated with aspirin, at high risk for cardiovascular events, enrolled in the HOPE Study.
I
Intervention
Upper quartile of urinary 11-dehydro thromboxane B2 levels (marker of in vivo thromboxane generation)
C
Comparator
Lower quartile of urinary 11-dehydro thromboxane B2 levels
O
Outcome
Composite of myocardial infarction, stroke, or cardiovascular death during 5 years of follow-upcomposite
Elevated urinary 11-dehydro thromboxane B2 levels in aspirin-treated patients predict a higher risk of future myocardial infarction or cardiovascular death, suggesting aspirin resistance.
Main Result
Effect estimate: OR 1.8 (95% CI 1.2 to 2.7)
p-value: p=0.009
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. 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.