No revolution yet from drug elution

The SIROCCO study is the first drug-eluting stent trial in the periphery sponsored by Cordis and used a sirolimus-eluting nitinol SMART stent. The purpose of the SIROCCO trial was the long-term evaluation of self-expanding sirolimus-eluting nitinol SMART stents versus bare SMART stents in the SFA. Stephan Duda presented the 18-month angiographic results of SIROCCO II at this year's CIRSE meeting. For SIROCCO I, the binary restenosis rates for the slow-sirolimus release kinetic had appeared very promising up to 18 months (0%). Unfortunately, Duda then announced at last year's CIRSE annual meeting in Belek, Turkey, that the binary restenosis rate had risen to 40% in the slow sirolimus-eluting stent (SES) group at 24 months.

For SIROCCO II the restenosis rates in the slow sirolimus eluting stent arm had also appeared promising initially. Six-month data from the SIROCCO II trial, which enrolled a larger number of patients than the earlier trial, appeared to confirm the finding of SIROCCO I of the benefit of a slow-release formulation at six months with a binary restenosis rate of 0% vs. 7.7% for bare metal stents. Results at nine months published in the CIRSE abstract book showed a continued trend for greater efficacy of the sirolimus eluting stent with in-stent restenosis of 7.7% and 13% in the sirolimus arm and the control group, respectively. However the 18-month Duplex ultrasound data that Duda presented in Barcelona showed non-superiority between the DES arm and control with a total in-stent binary restenosis rate of 20.7% in the sirolimus-eluting stent arm and 17.9% rate in the bare metal stent arm (which included one total occlusion). The 24-month data were presented by Johannes Lammer at the European Congress of Radiology (ECR) meeting in Vienna in March and these showed a total in-stent binary restenosis rate of 24% in the sirolimus-eluting stent arm and 25% rate in the bare metal stent arm

More encouraging was the reported reduction in the number of stent fractures in SIROCCO I vs. SIROCCO II. There were five reported stent fractures in SIROCCO II at six months and one additional stent fracture detected by the core lab via biplanar flat x-ray at 18 months. This resulted in a 10.7% stent fracture rate in SIROCCO II when a maximum of two stents were used vs. 19% in SIROCCO I when a maximum of three stents were used.

The GREAT renal study is the first study comparing bare stents to drug-eluting stents (DES) in renals. Last year the six-month follow-up results were presented by Dr Marc Sapoval at the Charing Cross and these have now been published of the Palmaz Genesis peripheral stainless steel balloon expandable stent, comparing a sirolimus-coated versus an uncoated stent in renal artery treatment. Results at six months look promising for drug-eluting stents. The DES arm showed an in-stent binary restenosis rate of 6.7% versus 14.3% in the bare arm. Mean in-stent diameter stenosis was 18.7% for DES versus 23.9% for bare. Finally, the clinical patency rate was 96.2% in the sirolimus-eluting arm versus 92.3% in the bare arm. No fatal events related to the device or procedure were reported up to six months post-implantation in either arm. Dr Markus Zähringer, Assistant Medical Director for Cologne University's Institute for Radiologic Diagnostic Clinical Center, presented the latest results at ECR last month. The data showed a trend towards reduction of reintervention at one year (3.7% for the DES arm versus 11.5% in the bare arm). Speaking at the AIVS meeting after ECR Dr John Rose criticised the trial for choosing angiographic endpoints instead of clinical endpoints such as time to dialysis as the primary endpoints. Also the patient numbers were not large enough to reach statistical significance. Only trends were shown.

In conclusion, the researchers said some of the problems that need to be addressed for DES to work in the periphery include drug loading capacity, limitations of coatings, toxicity and stent structure. An alternative may involve drug coating of angioplacy balloons. A recent study looked at porcine coronary arteries, using paclitaxel coated balloons which lose only 6% of the dose during introduction to coronary arteries. Eighty per cent of the drug is released during inflation of the balloon, with early growth initiating events inhibited. The degree of neointimal reduction appears to be comparable to conventional DES in the porcine model.

This Charing Cross provides an important opportunity to assess the impact of DES in the periphery.