European high-activity (32)P radioactive stent experience

Brachytherapy by implantation of a radioactive stent is an alternative approach to catheter-based systems to reduce restenosis. The pilot clinical trials using 32P radioactive b-emitting stents at low-to-intermediate activity (0.5Eth 3.0 mCi) showed that restenosis at 6 months was not different from that of currently available non-radioactive stents. The evaluation of the efficacy in reducing restenosis of radioactive stents with higher activities (3Eth 24 mCi) started in Europe (Milan, Rotterdam and Vienna) between 1998 and 1999. In the Milan and Rotterdam experience, 32P radioactive stents with an activity of 3Eth 12 mCi demonstrated a reduction of intra-stent restenosis to < 4%. However, a high-edge restenosis > 30% was observed in the first 1Eth 3 mm outside the stent margins. This edge effect might be due to a low dose of radiation at the stent margins combined with systematic balloon injury in the reference segments. The hypothesis that a further increase in stent activity (12Eth 21 mCi) associated with a reduced balloon injury outside the stent could solve the problem of edge restenosis was not confirmed by the Milan experience; edge restenosis still occurred in 26% of the lesions treated by a single 32P radioactive stent, even if a nonaggressive stent implantation strategy was used. Two approaches under investigation to solve the problem of edge restenosis are: 1) lengthening the stent with a non-radioactive stent (cold-ends stent) to prevent negative remodeling; and 2) extending the area of irradiation beyond the balloon-injured area by an increased activity at the stent ends (hot-ends stent).