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 A(2) (TXA(2)) synthesis, (2) platelet recruitment elicited by TXA(2)-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. TXA(2) synthesis and platelet recruitment (fluid-phase proaggregate activity of cell-free releasate) were assessed after collagen stimulation (1 micro g/ml) of whole blood. Partial inhibition of TXA(2) 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 TXA(2) production. This was independent of fibrinolysis, and platelet COX-2 expression was not augmented. TXA(2) 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 TXA(2) blockade, which was also associated with increased myonecrosis. In conclusion, ASA resistance, elicited by TXA(2)-dependent and TXA(2)-independent mechanisms, was prevalent in patients with STEMI. This study describes, for the first time, the association of partial platelet TXA(2) inhibition with myonecrosis.
Valles
Juana
J
Research Center, University Hospital La Fe, Valencia, Spain.
Santos
M Teresa
MT
Fuset
M Paz
MP
Moscardo
Antonio
A
Ruano
Miguel
M
Perez
Francisca
F
Piñon
Marta
M
Breña
Silvia
S
Aznar
Justo
J
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001241:Aspirin / Q000008:administration & dosage / Q000627:therapeutic use*; D001792:Blood Platelets / Q000502:physiology*; D016022:Case-Control Studies; D004351:Drug Resistance; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D009206:Myocardium / Q000473:pathology; D009336:Necrosis; D010974:Platelet Aggregation / Q000502:physiology; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D012720:Severity of Illness Index; D013928:Thromboxane A2 / Q000097:blood*
D010975:Platelet Aggregation Inhibitors; D013928:Thromboxane A2; D001241:Aspirin