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.