Effect of Atorvastatin on Platelet Thromboxane A2 Synthesis in Aspirin-Treated Patients With Acute Myocardial Infarction

Inhibition of platelet thromboxane A2 (TXA2) by aspirin is critical in patients with acute myocardial infarction (AMI), but some patients have persistent platelet TXA2 production within 48 hours of the onset of AMI. Statins are known to reduce TXA2 in aspirin-free patients with hypercholesterolemia. We hypothesized that treatment with aspirin plus atorvastatin could reduce persistent TXA2 synthesis and aspirin resistance in patients with AMI. We evaluated platelet function in 184 aspirin-treated patients within 48 hours of the onset of AMI. Patients were divided into group A (treated with aspirin alone, n = 139) and group B (treated with aspirin plus atorvastatin, n = 45). We studied collagen-induced platelet TXA2 synthesis, serotonin (14C-5HT) release and recruitment, and adenosine diphosphate-, arachidonic acid-, and collagen-induced platelet aggregation. Persistent TXA2 synthesis was detected in 25% and 9% of groups A and B, respectively (p = 0.03). TXA2, arachidonic acid-aggregation, and collagen-induced responses were significantly reduced in patients receiving dual treatment compared to those receiving aspirin monotherapy. Atorvastatin did not modify platelet reactivity in patients with efficiently blocked TXA2 synthesis. These results strongly suggest a direct effect of the statin on platelet eicosanoid synthesis. This was confirmed in vitro by incubating washed aspirin-free and aspirin (1 μM)-treated platelets from normal subjects with 1 to 20 μM atorvastatin. Atorvastatin in vitro significantly reduced platelet TXA2 synthesis and collagen-induced aggregation. In conclusion, atorvastatin combined with aspirin early in the onset of the acute event significantly reduced persistent TXA2 and TXA2-dependent aspirin resistance. This could contribute to the clinical benefit of atorvastatin in patients with AMI.