Ideally, cardiologists would like a stent that is easy to deliver, causes no acute thrombosis, provides insignificant late loss due to intimal hyperplasia and offers no risk of late thrombosis should antiplatelet therapy have to be withdrawn.
       Drug-eluting stents (DES) are currently coated with antiproliferative agents that inhibit inflammation and cellular proliferation after stent implantation and have convincingly been shown to reduce neointimal hyperplasia, the incidence of in-stent restenosis and to improve long-term outcomes.^1,2 The active agent is often mixed with a synthetic polymer to control drug elution in a time- and dose-dependent manner. Unfortunately, many of these polymers are nonerodable, and some have been shown to induce inflammation and neointimal hyperplasia in animal models.³ This has led to concern that nonbiodegradable polymer coatings may be associated with chronic inflammation, delayed vessel healing and an increased risk of late stent thrombosis.⁴ This latter phenomenon has worryingly already been reported with DES after discontinuation of antiplatelet medication.^5,6
       The present study demonstrates that a synthetic stent polymer — poly (L-Lysine)-g-poly (ethyleneglycol) (PLL-g-PEG) without an antiproliferative agent — can markedly reduce neointimal hyperplasia, and is not associated with early inflammation or thrombosis.⁷ The proposed mechanism of action is that the polymer coating prevents binding of circulating proteins and cells to the stent, a process known as polymeric steric stabilization. Although the results are promising, similar minimal late loss would have to be demonstrated to occur in atherosclerotic coronary arteries over a prolonged period of follow up in animal studies to warrant safety and efficacy trials in humans. Concerns remain over the long-term effects of such a nonbiodegradable polymer, and the fact that it inhibits cell adhesion may impair stent endothelialization and increase the risk of late stent thrombosis. Nevertheless, if such a minimal amount of neointimal hyperplasia was the norm late after implantation in human atherosclerotic arteries, it might provide the solution to some of the concerns over DES. However, this small amount of data on nonatherosclerotic coronary arteries in 7 pigs studied only up to 6 weeks after implantation are of little clinical relevance. For example, there are significant differences in the time response to healing after vascular injury in humans and pigs with peak neointimal growth occurring after 28 days in the pig model compared to 6–12 months in humans.⁸ A “late catch-up” phenomenon has been reported in the porcine model of restenosis with polymer-based sirolimus-eluting stents inhibiting neointimal hyperplasia at 30 days and not at 90 and 180 days.⁹
       It seems unlikely that the results demonstrated in this small study would be replicated in the sort of advanced coronary artery disease that faces interventionists in clinical practice where patient, lesion and procedural factors, as well as stent characteristics, all impact on the local cellular response to stent deployment and subsequent neointimal growth. The solution may lie in more sophisticated stents that deliver an antiproliferative agent to the artery wall for the important period post-stent deployment. This would limit neointimal hyperplasia to a microlayer sufficient enough to cover the stent struts, which preferably should be coated in an inert material that does not stimulate inflammation and/or thrombosis. Whether the attraction of endothelial progenitor cells to stent struts to encourage endothelial cell coverage of the exposed metal will restrict neointimal hyperplasia and prevent thrombosis, whether such technology will need to be combined with antiproliferative drug elution into the artery wall from the ablumenal surface of the stent, whether the drug should be released from a nonbiodegradable or a biodegradeable polymer or from the metal itself, or whether the stent itself should be biodegradable remains to be established. It will be interesting to see the results of further experimental studies with stents coated with PLL-g-PEG implanted in atherosclerotic arteries and, if successful, whether investment is forthcoming to pursue its evaluation in human clinical trials.

References
1. Moses JW, Leon MB, Popma JJ, et al. Sirolimus-eluting stents versus standard stents in patients with stenosis in a native coronary artery. N Engl J Med 2003;349:1315–1323.
2. Stone GW, Ellis SG, Cannon L, et al. Comparison of a polymer-based paclitaxel-eluting stent with a bare metal stent in patients with complex coronary artery disease: A randomized controlled trial. JAMA 2005;294:1215–1223.
3. van der Giessen WJ, Lincoff AM, Schwartz RS, et al. Marked inflammatory sequelae to implantation of biodegradable and nonbiodegradable polymers in porcine coronary arteries. Circulation 1996;94:1690–1697.
4. Virmani R, Guagliumi G, Farb A, et al. Localized hypersensitivity and late coronary thrombosis secondary to a sirolimus-eluting stent: Should we be cautious? Circulation 2004;109:701–705.
5. McFadden EP, Stabile E, Regar E, et al. Late thrombosis in drug-eluting coronary stents after discontinuation of antiplatelet therapy. Lancet 2004;364:1519–1521.
6. Pfisterer ME, for the BASKET-LATE Investigators. BASKET-LATE: Late clinical events related to late stent thrombosis after stopping clopidogrel: Prospective randomized comparison between drug-eluting versus bare-metal stenting. Program and abstracts from the American College of Cardiology 55th Annual Scientific Session, March 2006, Atlanta, Georgia. Abstract 422–11. http://www.medscape.com/viewarticle/529648.
7. Billinger M, Buddeberg F, Hubbell JA, et al. Polymer stent coating for prevention of neointimal hyperplasia. J Invasive Cardiol 2006;18:423–426.
8. Lowe HC, Schwartz RS, MacNeill BD, et al. The porcine coronary model of in-stent restenosis: Current status in the era of drug-eluting stents. Catheter Cardiovasc Interv 2003;60:515–523.
9. Carter AJ, Aggarwal M, Kopia GA, et al. Long-term effects of polymer-based, slow-release, sirolimus-eluting stents in a porcine coronary model. Cardiovasc Res 2004;63:617–624.