Question: Among high-risk patients with vascular disease treated with aspirin, is incomplete suppression of thromboxane generation associated with an increased risk of recurrent cardiovascular events? Population: Men and women 55 years of age who had a history of coronary artery disease, stroke, peripheral vascular disease, or diabetes plus at least one other CV risk factor who participated in the HOPE trial which was a 2 2 factorial randomized controlled trial of ramipril and vitamin E.1 Design and methods: Nested case-control study of the 5529 patients from the HOPE trial participants from Canada in whom a urine sample was collected at baseline. All samples were sent to a central laboratory and stored at -80°C. Only those patients who were taking aspirin were included. Cases were defined as individuals who had a confirmed MI, stroke, or CV death after randomization. Control subjects were randomly selected from aspirin-treated patients who provided adequate urine samples but did not suffer MI, stroke or CV death after randomization. Cases and controls were matched according to sex and age (5 years) in a ratio of 1:1. Urine was thawed and assayed for 11-dehydro thromboxane B2 levels using the Caymann Chemical immunoassay. Results: Among 488 cases and 488 matched controls, the odds of an MI, stroke or CV 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: 1.2-2.7, p = 0.009). Conclusion: Among aspirin-treated patents who have established vascular disease, urinary 11- dehydro thromboxane B2 predicts the future risk of MI and CV death, and may reflect ‘aspirin resistance’.
