95 Delayed Therapy with Clopidogrel and Everolimus Substantially Inhibits the Development of Transplant Arteriosclerosis

Abstract

Purpose Our group has shown that combination of clopidogrel and everolimus dramatically reduced the development of transplant arteriosclerosis (TxA). The aim of this study was to investigate whether a delayed onset of treatment- similar to the clinical setting - could inhibit progression of TxA. Methods and Materials Fully allogeneic C57BL/6 (H2(b)) donor aortas were transplanted into CBA (H2(k)) recipients. Recipients were treated with Clopidogrel (1 mg/kg/d) and Everolimus (0.05 mg/kg/d), alone or in combination, starting on postoperative days 1, 7 or 14. Grafts were analyzed by histology and morphometry on day 30 after transplantation. Results In mice treated with clopidogrel alone, TxA was significantly reduced as compared to untreated controls when therapy was started on day 1 (intima proliferation 56%±11% vs. 81%±7% [control]/n=5). This effect was also seen when clopidogrel therapy was started on postoperative day 14 (intima proliferation 50%±4% vs. 81%±7% [control]/n=5). Combination of clopidogrel and everolimus dramatically reduced the formation of TxA when medication was started on day 1 (intima proliferation: 11% ± 8% vs. 81% ± 9% [control], n = 5) and showed remarkable reduction in both delayed onset groups (on day 7: intima proliferation: 36% ± 10% vs. 81% ± 9% [control], n = 5 and on day 14: intima proliferation: 44% ± 3% vs. 81% ± 9% [control], n = 5). Conclusions These results demonstrate that even delayed onset of treatment with clopidogrel and everolimus – representative for a clinical setting - results in a strong reduction of TxA in this murine aortic allograft model.