If the stent could be coated with a drug that inhibits neointimal proliferation in such a way that the active substance would diffuse slowly and locally, so that small doses could be used, that might reduce the failure rate with stents. Clinical interest has focused on two drugs—namely, sirolimus, which began life as an immunosuppressive agent to prevent the rejection of transplanted organs, and the anticancer agent paclitaxel. However, many other agents have been experimented with in stents, such as radionculides, nitric oxide emitters, platelet inhibitors, and everolimus; and in clinical circumstances where regrowth is actually desirable, added fibroblast growth factor has been tried.

The RAVEL Study Group placed a 5-micrometer-thick layer of sirolimus-carrying polymer onto a stainless steel stent. A layer of polymer on top ensured slow diffusion such that about 80% of the drug would be released in 30 days. In clinical trials in this area there is a choice of endpoint; you can measure things like vessel diameter or you can count events such as the need for a further revascularization procedure, or do both. Luminal loss (reduction in the internal diameter of the vessel) was significantly less in the sirolimus group. The difference between the rate of major cardiac events, the clinical endpoint, was 5.8% (sirolimus) versus 28.8% (control), "due entirely to a higher rate of revascularization of the target vessel in the standard-stent group." With stenting, thrombosis is an adverse event that trialists watch out for, but there were no such incidents in either group in the RAVEL trial.

I am aware of no head-to-head trials of sirolimus against the other frontrunner in this area, the paclitaxel-eluting stent. There are plenty of trials with both agents so one example with paclitaxel must suffice. TAXUS-IV is a randomized trial whose one-year clinical results were published in April of this year (G.W. Stone, et al., Circulation, 109[16]: 1942-7, 2004). Again, there were no safety concerns, and target vessel revascularization rates were 7.1% in the active group and 17.1% in the controls, a reduction of 62%. The sirolimus stent is now on the market, and "real world" experience, as opposed to the somewhat artificial formal clinical trial settings, is now being recorded. One European center to have done a lot of work in this area is in Rotterdam, Netherlands. It is perhaps a compliment to the successes reported with drug-eluting stents that one question now being asked is what to do next in the event of placement of such a stent being followed by recurrent vessel narrowing. That question was posed earlier this year (A.T. L. Ong, et al., Herz, 29(2): 187-94, 2004), and at the time of writing the Rotterdam group had just released their experience of repeat drug-eluting procedures, in 24 patients (P.A. Lemos, et al., Circulation, 109[21]: 2500-2, 2004).