Insufficient Inhibition by Aspirin of Platelet TXA₂ Synthesis and Platelet Recruitment Is Associated with Myonecrosis in Patients with ST-Segment Elevation Myocardial Infarction.

Heterogeneity in response to aspirin (ASA) treatment or “aspirin resistance” could be of importance in patients with ST-segment elevation myocardial infarction (STEMI). Reduced effect of ASA in platelets could be due to partial inhibition of cyclooxygenase-1 (COX-1) or to COX-1-independent mechanisms. We evaluated the effect of ASA treatment in patients with STEMI for: a) platelet TXA₂ synthesis; b) platelet recruitment elicited by TXA₂-dependent and -independent mechanisms and c) the possible association of these aspects of platelet reactivity with serum markers of myonecrosis. We studied 62 consecutive ASA-treated patients shortly after the onset of the acute event. Analytical determinations were performed within 48 h of the onset of the acute event (mean ± SD, 23.12 ± 11.61 h). Fifty-two of the patients were treated with fibrin-specific fibrinolytic agents and 56 were also anticoagulated with enoxaparin. A group of 62 ASA-free and 10 ASA-treated controls were also evaluated. TXA₂ synthesis and platelet recruitment (fluid-phase pro-aggregatory activity of cell-free releasates) were assessed after collagen stimulation (1 μg/mL) of whole blood in patients and control subjects. Optimal inhibition of TXA₂ and platelet recruitment was assumed if these were greater than 95% and 80%, respectively, compared with the ASA-free population of normal donors. Comparisons between categorical data were performed using chi-squared tests. The Kruskal-Wallis non-parametric test was used for comparisons between groups. A two-sided P value < 0.05 was considered significant. Partial inhibition of TXA₂ by ASA was found in 21 patients (34%). This was associated with significant elevations of Troponin-T, CK-MB mass, CK and recruiting activity vs. 41(66%) patients with blocked TXA₂ production. This was independent of fibrinolysis and platelet COX-2 expression was not augmented. TXA₂ blockade was achieved after subsequent daily treatments or platelet incubation with ASA in vitro, suggesting reduced sensitivity of COX-1 to ASA. In addition, 28 patients (45%) had an abnormally elevated recruiting activity, despite TXA₂ blockade, which was also associated with increased myonecrosis. In conclusion, aspirin resistance, elicited by both TXA₂-dependent and TXA₂-independent mechanisms, was prevalent in patients with STEMI. This study describes for the first time the association of partial platelet TXA₂ inhibition with myonecrosis.