Association between the efficacy of dual antiplatelet therapy and the development of in-stent neointimal hyperplasia in porcine coronary arteries

OBJECTIVE: We set out to compare the effectiveness of platelet aggregation therapy in association with the development of in-stent neointimal hyperplasia in porcine coronary arteries. METHODS: Thirty-two pigs underwent coronary stenting with bare-metal stents under general anaesthesia. One hundred milligrams of aspirin and loading doses of either 300 mg clopidogrel (group C, n=13) or 2 x 500 mg ticlopidine (group T, n=19) were administered before intervention. During the follow-up, the animals received a daily dose of 100 mg aspirin and 75 mg clopidogrel or 2 x 250 mg ticlopidine, respectively. After 4 weeks, the histopathological and histomorphometric parameters of the explanted stented coronaries were assessed. Levels of circulating cytokines and platelet activation factors were measured. ADP-induced and collagen-induced aggregation was measured immediately before stenting and then every 3rd day. The aggregation profiles were calculated and correlated with the histological parameters. RESULTS: The fibrin deposition scores and inflammation scores were higher in group T than in group C, with similar injury scores. Endothelialization was complete in both groups. A significantly lower neointimal area (1.08+/-0.36 vs. 1.58+/-0.5, group C vs. T, P=0.026) and percentage of area stenosis (29.8+/-12.1 vs. 44.3+/-16.3, group C vs. T, P=0.032) were observed in group C. The loading dose of clopidogrel significantly reduced the platelet activation parameters before the first angiography as compared with ticlopidone. Clopidogrel treatment resulted in a significantly better aggregation profile relative to ticlopidine (mean ADP-induced aggregation: 28.4+/-9.1 vs. 52.5+/-12.0%, P<0.001). Significant (P<0.05) positive linear correlations were observed between the ADP-induced aggregation profile and the neointimal area (r=0.584), percentage of area stenosis (r=0.666), inflammation (r=0.476) and fibrin deposition (r=0.496). CONCLUSION: The effectiveness of dual antiplatelet therapy plays an important role in the inhibition of in-stent neointimal hyperplasia.