Key result
Patients with coronary heart disease on long-term low-dose aspirin exhibited enhanced variability and higher mean serum TXB2 levels (8.5 ng/mL) compared to healthy subjects (3.2 ng/mL).
Why the study?
Is there heterogeneity in the suppression of platelet COX-1 activity by aspirin in patients with coronary heart disease compared to healthy subjects?
Observational (n=40)
Is there heterogeneity in the suppression of platelet COX-1 activity by aspirin in patients with coronary heart disease compared to healthy subjects?
Absolute Event Rate: 8.5% vs 3.2%
A significant proportion of patients with coronary heart disease exhibit inadequate suppression of platelet COX-1 activity by low-dose aspirin, highlighting heterogeneity in aspirin responsiveness.
May indicate incomplete aspirin response in some CHD patients; hypothesis-generating for monitoring strategies before practice change.
BACKGROUND AND OBJECTIVES: Complete and persistent suppression of platelet thromboxane (TX) A(2) biosynthesis by aspirin is mandatory to fulfill its cardioprotection. We explored the determinants of heterogeneity of TXB2 generation in clotting whole blood, a capacity index of platelet cyclooxygenase (COX) activity, in patients with coronary heart disease (CHD) versus healthy subjects treated with low-dose aspirin on a long-term basis. METHODS: We studied 30 patients with CHD (ie, chronic stable angina, unstable angina, and acute myocardial infarction) and 10 healthy subjects, who were treated with low-dose aspirin (100 mg daily) on a long-term basis, 12 hours after the administration of 160 mg aspirin to ensure saturation of platelet COX-1 activity. Serum TXB2 levels were assessed. The contribution of blood COX-2 to TXA2 biosynthesis was explored by evaluation of the effect of a selective COX-2 inhibitor (L-745,337) added to heparinized whole blood stimulated with Ca++ ionophore A23187 (20 micromol/L) for 1 hour or lipopolysaccharide (0.1 microg/mL) for 4 hours. RESULTS: In healthy subjects serum TXB2 levels ranged from 0.6 to 7.9 ng/mL (median, 2.1 ng/mL; mean +/- SD, 3.2 +/- 2.6 ng/mL). In CHD patients we detected enhanced variability in serum TXB2 generation (median, 3.1 ng/mL [range, 0.15-47 ng/mL]; mean, 8.5 +/- 12.3 ng/mL), which in 8 patients (27%) exceeded the mean value + 2 SDs detected in healthy subjects (ie, 8.4 ng/mL), set as the limit value for an adequate inhibition of platelet COX-1 by aspirin. Elevated whole-blood TXB2 generation was not dependent on leukocyte count, COX-2 activity, or cigarette smoking but was plausibly a result of defective suppression of platelet COX-1 activity. CONCLUSIONS: Heterogeneity in the suppression of platelet COX-1 activity by aspirin occurred in CHD patients. The measurement of the serum TXB2 level seems to be an appropriate biomarker to identify patients who have an inadequate inhibition of platelet COX-1 activity by aspirin.
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Sciulli et al. (2006) conducted an observational in Coronary heart disease (n=40). Coronary heart disease vs. Healthy subjects was evaluated on Serum TXB2 levels. Patients with coronary heart disease on long-term low-dose aspirin exhibited enhanced variability and higher mean serum TXB2 levels (8.5 ng/mL) compared to healthy subjects (3.2 ng/mL).
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