Many vascular specialists have expected drug-eluting stents to revolutionise stent outcome in the treatment of peripheral vascular disease following the excellent results of the RAVEL and SIRIUS studies, which looked at the use of drug-eluting stents for percutaneous coronary interventions. The Sirolimus Coated Cordis SMART Nitinol Self-expandable Stent for the Treatment of Obstructive Superficial Femoral Artery Disease (SIROCCO) trial was billed as a landmark in vascular intervention after the six-month results were first published. The 18-month results indicate that getting the right drug, the right polymer and the right stent design is not enough. Now the speed of drug elution seems to be a critical factor.
Stephan Duda, Professor of Radiology and Vice Chairman of the Department of Diagnostic Radiology of the University of Tuebingen, Germany, presented the long-term results of the SIROCCO trial at the 15th International Symposium on Endovascular Therapy (ISET) held in Miami Beach, Florida.
Of the 36 patients in this double blind, randomised, prospective, feasibility trial for sirolimus-eluting stents in the SFA, 14 in the sirolimus-eluting arm and 17 in the control were analysed by duplex ultrasound at 18 months. In the slow sirolimus-eluting group (five patients) there was 0% restenosis, although in the fast sirolimus-eluting group (nine patients) three patients (33%) demonstrated restenosis. The restenosis rate in the control group (17 patients) was 30%.
Duda told Vascular News: “Overall, we are very encouraged by the SIROCCO findings. The results provide additional insight into the treatment of a vascular disease that, until now, has been associated with very poor results when using an endovascular approach. The 18-month data for patients who received the slow-release formulation of the sirolimus-eluting stent were very promising. This cohort showed 0% restenosis at six-month follow-up, and this finding was continuing to hold at 18 months.
The primary endpoints of this trial were safety and in-stent percent mean diameter stenosis via quantitative angiography determined within six months of stent placement. The in-stent percent mean diameter stenosis, measured after six months of treatment, was 11.7% for patients receiving the slow-eluting sirolimus-eluting Cordis SMART stent, compared with 27.5% for patients who received the fast-eluting sirolimus stent and 30.9% for patients receiving the plain nitinol stent.
The SIROCCO trial has now been expanded and an additional 57 patients have been randomised, bringing the total up to 93. “We are very optimistic about the use of the sirolimus-eluting stent in treatment for SFA,”said Duda, “In fact, we have extended the trial and have randomised an additional 57 patients utilising the slow-release formulation.
The addition of these 57 patients, and five additional trial sites, will be sufficient to confirm that the slow-release formulation is effective in suppressing neointimal hyperplasia, said Duda
The results of SIROCCO support the use of slow-sirolimus eluting stents in the SFA, but not the fast-eluting stents. Duda explained: “SFA disease is typically associated with thrombus, plaque, and calcification. In fact, the sirolimus-treated patients in SIROCCO all had moderate-to-heavy calcification of the SFA. It appears particularly important that a slow-elution formulation of sirolimus be used in the SFA to allow sufficient drug levels to diffuse into the vessel wall. After analysing the findings for the fast-release formulation, we concluded that the drug was released too quickly to allow sufficient tissue levels to be reached in the vessel wall.”
Asked what the next steps for the SIROCCO trial would be, Duda said: “Once the six-month angiographic data on the additional 57 patients randomised to treatment with the slow-release formulation confirm sufficient efficacy, the next step will be to conduct a large, multicentre, randomised, controlled trial in the US”
If the SIROCCO trial proves that slow sirolimus-eluting stents perform well in the superficial femoral arteries, a region renowned for in-stent restenosis, they will probably perform well elsewhere. It may mean more stents are used in treating lower limb occlusions, although some lesions might be considered unsuitable following the initial experiences of trials in peripheral applications. Barry Katzen, Medical Director of the Miami Cardiac & Vascular Institute, Baptist Hospital, Miami, and ISET director, has said that if drug-eluting stents prove of benefit in the treatment of the SFA, they will be achieving the “holy grail.
However, one of the great innovators in transluminal revascularisation has voiced doubt about the future of drug-eluting stents, asking if they are an evolutionary dead-end. Julio Palmaz developer of the balloon expandable stent says that he sees drug-eluting stents as an evolutionary dead-end because it appears that drug elution will not work on all devices. On receiving the ISET Innovator Award for 2003, Palmaz pointed out that whilst drug elution works on small stents in the coronary system, it is still an open question whether it will work on longer stents for peripheral vascular disease. He also felt that it was unlikely that drug elution would work on endovascular stent grafts, surgical prosthetic substitute conduits, mechanical hearts or left ventricular assist devices.
Palmaz feels that there is “a need to engineer the surface rather than drugs to achieve the effect”of eradicating restenosis. This means engineering a biocompatible response by understanding protein structures and customising a domainal pattern. Palmaz described the development of chemically defined surface domains as “work in progress. He also feels that nanotechnology could also be used to develop stents as platforms for the following: