P2088Once daily low-dose aspirin reduces urinary thromboxane B2 effectively even at 12-24 hours from dosing in the ASCEND (A Study of Cardiovascular Events iN Diabetes) trial

Abstract

Background: Aspirin is widely used for cardioprotection, with its anti‐platelet effects due to the blocking of thromboxane A2 production. The extent of thromboxane A2 inhibition can be assessed by measuring the urinary excretion of 11‐ dehydro‐thromboxane B2 (UTxB2), with UTxB2 <1500 pg per mg creatinine indicating effective suppression. Purpose: Previous trials have been interpreted as suggesting that aspirin is less effective in diabetes patients due to their upregulated megakaryocytic thromboxane production and faster recovery of its effect, leading to the suggestion that aspirin may need to be given twice daily in these patients. We assess the effectiveness of once daily aspirin to suppress UTxB2, particularly at 12‐24 hours after ingestion, in the context of a large randomized trial. Methods: ASCEND is an on‐going randomized trial in 15,480 people with diabetes but no occlusive arterial disease, investigating the effects of 6‐10 years of enteric coated aspirin 100 mg once daily vs placebo on cardiovascular events, cancer and bleeding. We assayed UTxB2 using competitive ELISA assay in mailed paired urine samples at baseline and a mean of 2 years after randomization from 152 randomly selected participants (76 aspirin vs 76 placebo). Only date of urine sample is known therefore some who ingested their tablet the same day may have taken the tablet after their urine sample. Effective suppression and differences in UTxB2 by treatment allocation were analysed by chi‐square tests and linear regression respectively. Results: Amongst placebo allocated participants not taking aspirin, follow‐up and baseline UTxB2 levels were correlated (correlation coefficient of log UTxB2 = 0.5, p<0.0001). During follow‐up, 82% allocated aspirin versus 7% allocated placebo achieved effective suppression with UTxB2 71% (95% CI 64 ‐ 76%) lower in those allocated aspirin than in the placebo arm (p<0.0001). This suppression was only apparent in compliant participants (heterogeneity in the effect of aspirin allocation between compliers and non‐compliers p<0.0001), with 86% of aspirin arm compliant participants achieving effective suppression, compared to 2% of placebo arm compliant participants. In compliant participants who ingested their last tablet the day before urine sampling, 88% of those allocated aspirin achieved effective suppression and UTxB2 was 76% (95% CI 65‐84%) lower than in those allocated (and compliant with) placebo. Conclusion: Daily aspirin significantly reduces UTxB2 in participants with diabetes, up to 12‐24 hours after ingestion. The final results of ASCEND will show whether this translates into a reduction in cardiovascular events in this population.