Partial Inhibition of Platelet Thromboxane A2 Synthesis by Aspirin 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). Decreased effects of ASA in platelets could be due to partial inhibition of cyclo-oxygenase-1 (COX-1) or to COX-1–independent mechanisms. We evaluated the effect of ASA treatment in patients with STEMI for (1) platelet thromboxane A2 (TXA2) synthesis, (2) platelet recruitment elicited by TXA2-dependent and -independent mechanisms, and (3) a possible association of these aspects of platelet reactivity with serum markers of myonecrosis. We studied 62 ASA-treated patients within 48 hours of onset of the acute event and 69 ASA-free and 10 ASA-treated controls. TXA2 synthesis and platelet recruitment (fluid-phase proaggregate activity of cell-free releasate) were assessed after collagen stimulation (1 μg/ml) of whole blood. Partial inhibition of TXA2 by ASA was found in 21 patients (34%). This was associated with significant increases in troponin T, creatine kinase-MB mass, creatine kinase, and recruiting activity versus 41 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 lower sensitivity of COX-1 to ASA. In addition, 28 patients (45%) had an abnormally increased recruiting activity despite TXA2 blockade, which was also associated with increased myonecrosis. In conclusion, ASA resistance, elicited by 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.