RAVEL trial

Rapamycin (sirolimus), a macrolide antibiotic, has been used recently in organ transplantation for its potent immunosuppressive actions by inhibiting both cytokine mediated and growth factor mediated proliferation of smooth muscle cells and lymphocytes [55, 56]. In the RAVEL trial of non-acute single vessel lesions, the Sirolimus-eluting stent was compared to bare metal stent (BMS) in a 1 1 fashion [57]. One-year major adverse cardiovascular events and 6 month neointimal proliferation as assessed by late luminal loss (-0.01 0.33 mm in Sirolimus stent versus 0.80 0.53 mm in BMS) were improved. The Sirolimus-eluting stent thus virtually eliminated in-stent restenosis with no evidence of edge effect, dissection, or in-stent thrombosis. 

Surruys PW, Degertekin M, Tanabe K, et al. Intravascular ultrasound findings in the multicenter randomized, double-blind RAVEL trial. Circulation 2002 106 798-803. 

In long-term follow-up of the RAVEL trial (73), clinical benefit with sirolimus-eluting coronary stents has been maintained. Using cumulative one to three-year event-free survival rates, treatment with sirolimus-eluting stents was associated with a sustained clinical benefit and very low rates of target lesion revascularization up to three years after device implantation. As recently shown by both Kastrati and coworkers (74) and Windecker et al. (75), the Cypher stent eluting sirolimus is highly effective and may have clinical benefit beyond alternative DES products. 

FajadetJ, Morice MC, Bode C, et al, Maintenance of long-term clinical benefit with sirolimus-eluting coronary stents three-year results ofthe RAVEL trial, Circulation 2005 I I I (8) 1040-1044,... 

The first clinical study was the RAVEL trial, which showed that no cases of restenosis were observed with the DES, but 26.6% of BMS cases suffered from restenosis [31]. A 3 year follow-up of the RAVEL study showed sustained clinical benefits [35], during which another set of trials called the SIRIUS study compared the safety and efficacy of the sirolimus eluting stent with two smaller studies that were performed in Europe (E-SIRIUS) and Canada (C-SIRIUS) [36-39]. The combined results showed a reduction in in-stent restenosis from 38.5% (BMS) to 3.1% (sirolimus eluting stent). 

Morice MC, Serruys PW, Sousa JE, et al. A randomized comparison of a sirolimus eluting stent with a standard stent for coronary revascularization the RAVEL trial. N Engl J Med 2002 346(23) 1773-80. 

In a subset of RAVEL, three-dimensional IVLfS was used to characterize post-stent characteristics at 6 months [58]. Binary re-stenosis and late angiographic loss with the sirolimus stent was again eliminated at 6 months compared to the BMS (0% and 0.06 0.30 mm versus 23.4% and 0.91 0.58 mm) despite having a 21% incidence of incomplete stent apposition at 6 months compared to only 4% in the standard stent. While other trials have demonstrated... 

Serruys PW, Degertekin M, Tanabe K, AbizaidA, SonsaE, Colombo A, et al. Intravascn-lar ultrasound findings in the multicenter, randomized, donble-bfind RAVEL (randomized study with the sirolimus eluting velocity balloon-expandable stent in the treatment of patients with de novo native coronary artery lesions) trial. Circulation 2002 106 798-803. 

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