Is Zero Enough?

In this issue, Huang et al. focus on new techniques to solve in-stent restenosis that are caused by neointimal hyperplasia. A major focus of interventional cardiology is to decrease the need of retreatment of coronary lesions. Stenting, increasingly used in the last decade, results in significant vascular injury and vessel wall alteration. The healing response results in inflammation, cell alteration and proliferation, especially at the site of injury the stent strut. In experimental studies and clinical trials, the extent of inflammation predicts the rate of complication and restenosis. Therefore, it is reasonable to expect a beneficial effect on the neointimal formation with local application of corticoids. The article by Huang and colleagues in this issue of the Journal of Invasive Cardiology is a paper concerning a smart approach of local modulation of the well characterized post-stenting inflammatory response. Stent-based local drug delivery has been proposed to prevent in-stent restenosis, and recent clinical studies have shown promising results. As the stent-strut as focus of inflammation contains the eluting drug, it is reasonable to expect a reduction concerning the response-to-injury. Besides the choice of drug, a major issue is the efficacy and characteristics of drug release. See Huang et al. on pages 505–513 As pharmacologic barriers, like the coating in this study, influence the amount, loading and release, it is of severe impact to study this in detail, as performed in this paper. Therefore, the remarkable influence of coating on speed of drug release, as presented by the authors, is relevant, even in the “post RAVEL” period. The presentation increased drug amount incorporation in a stent-coating that achieves a much higher local drug concentration. The choice of corticoids must, however, be seen in the background of the radiation experience, the “Ravel”-study and in the light of previous negative data of systemic corticoid application as loading dexamethasone into polymer-coated stents has reduced inflammatory reaction, but the effect on neointimal hyperplasia remains controversial. Local endoluminal or perivascular injection of various corticoids resulted in controversial effects on advential inflammation with adverse effects concerning neointimal hyperplasia. Therefore, the presented data concerning the choice of drug have to stand the test of time in a clinical environment. As the data are experimental, the basic question concerning the choice of corticoids is if the time for this kind of effort is wasted after persistent publication of 1 ± 3% versus 29 ± 20% mm3 volume obstruction or 2 ± 5 mm3 versus 37 ± 28 mm3 in six-month follow-up data of data, with nearly complete abolition of the proliferative process inside the stent and no relevant adverse effects, thrombosis or edge effect and a reduction of clinical events of over 20% and not a single target vessel revascularisation (Circulation August 13, 2002) no study ever could achieve such a drastic reduction to a zero level. However, a major concern with Ravel, Sirolimus, Sirius, E-Sirius, etc., is if the post-interventional process is only transiently suppressed and will appear only later. Therefore, until no negative late follow-up data or no apparent “dark-sides” are published, the current experimental approaches suffer a decline in clinical relevance and impact.