Prasugrel Aggravates the Inflammatory Response in a PG-PS-Induce Arthritis Model,

Abstract 3268

Prasugrel is a very potent and effective P2Y12 receptor antagonist, used primarily to prevent thrombotic events in patients managed for percutaneous coronary intervention (PCI). It is not recommended as prophylaxis antithrombotic therapy because prasugrel increases patient's risk of bleeding. Even though indication of prasugrel treatment has been limited to the PCI procedure, there are not reports of the effects of prasugrel in patients with associated inflammatory diseases that undergo for PCI. Thus, we evaluate the effects of prasugrel, for 21 days, in a peptidoglycan polysaccharide (PG-PS)-induced arthritis rat model. Lewis rats were randomly separated into four groups from which only half of the animals were induced with PG-PS. There was a significant increase in the inflammatory changes observed in the PG-PS-induced animals treated with prasugrel compared to the PG-PS-induced control including a) increase joint diameter associated with visible signs of inflammation (during days 4 to 6 [p<0.05] and days 13 to 21 [p<0.001]); b) microscopic studies of hind joints showed marked increase in histomorphometric measurements including leukocyte infiltration, synoviocyte hyperplasia, fibrosis and neovascularization (significant increase in vessel number and size); and c) significant increase in platelet count (1,047 ± 89.03 × 10³ vs. 710.8 ± 52.65 × 10³, p<0.05). Platelet factor 4 (PF4) plasma levels were increased in PG-PS induced control as well as in PG-PS treated with prasugrel animals, however no significant differences were observed between these two groups. Plasma levels of cytokines such as IL-1 beta, IL-6, MIP1 alpha, MCP1, and RANTES were increased in PG-PS-induced animals (both, control and prasugrel treated animals). Only MIP1 alpha levels were significantly increased with additional treatment of prasugrel (p<0.05). In contrast, IL-10 levels were lower in the PG-PS-induced treated with prasugrel (p<0.05). In summary, treatment with P2Y12 receptor antagonist drugs, such as prasugrel, increases the inflammatory changes in PG-PS-induced arthritis model. Further investigations are in need to elucidate the potential unwanted effect of the P2Y12 receptor antagonists in patients afflicted with inflammatory illnesses.