Abizaid Table 2 Rate of late-stent thrombosis: sirolimus-eluting, paclitaxel-eluting, drug-eluting, and bare metal stents Author Trial Patients (N) Length of Thrombosis rates by stent type follow-up (SES/PES/DES/BMS) Kereiakes et al 2006 Pooled analysis SES: 337 1080 days SES: 0% BMS: 0.4% BMS: 238 Moreno et al 2005 Meta-analysis DES: 2602 – DES: 0.58% SES: 0.11% BMS: 2428 BMS: 0.54% PES: 0.29% Park et al 2006 Single center, SES: 1545 18 months DES: 0.8% all comers PES: 366 Schampaert et al 2004 Pooled SES: 758 2 years SES: 0.4% analysis BMS: 752 BMS: 0.5% Bavry et al 2005 Meta-analysis SES: 1515 13.5 months SES: 0.07% BMS: 1448 BMS: 0.48% Weisz et al 2006 SIRIUS trial SES: 533 361–720 days SES: 0.9% BMS: 525 BMS: 1.5% Urban et al 2006 e-CYPHER SES: 15157 12 months SES: 0.19% registry lakovou 2005 Prospective SES: 1062 9 months SES: 0.8% observational PES: 1167 PES: 1.7% cohort study Abbreviations: BMS, bare metal stents; DES, drug-eluting stents; PES, paclitaxel-eluting stents; SES, sirolimus-eluting stents. lesions) add to the growing evidence in support of the use of SES in the treatment of multi-vessel disease. However, as with all “new” technologies, continued careful investigation will be an essential aid to appropriate patient selection and treatment when treating patients with more complex lesions and multi-vessel disease (Serruys et al 2005). Late loss: a key measurement in differentiating drug-eluting stents (DES) Late loss is the angiographic metric that allows post-stent neointimal hyperplasia to be most accurately and reliably quantiﬁed. It reﬂects the ability of DES to inhibit the inﬂam- matory and hyperplastic processes that translate into adverse clinical outcomes such as binary restenosis and target lesion revascularization (Mauri et al 2005). When the CYPHER vs TAXUS head-to-head trials are organized in order of increasing patient and lesion complex- ity (REALITY → SIRTAX → ISAR-DIABETES → ISAR- DESIRE) a trend emerges showing an association between lower late loss and superior clinical outcomes (restenosis and TLR). As the patient population becomes more complex, the gap between CYPHER and TAXUS in terms of late loss and restenosis widens, showing an increasing beneﬁt with the CYPHER stent (Fig. 2). It has been seen that there is an association between late loss, restenosis, and complexity in CYPHER vs TAXUS studies. Late loss and in-stent restenosis increase as patient populations become more complex, and these increases are consistently higher in TAXUS populations. This trend is expressed as a “complexity curve”. When the ENDEAVOR III results for late loss are mapped onto this complexity curve it can be seen that the late loss and restenosis rate are high considering the relatively straightforward patient population evaluated in ENDEAVOR III (Fig. 3). Key characteristics of an ideal DES To be successful, DES must combine several key character- istics. The ﬁrst requirement is for a drug that reliably blocks smooth muscle cell hyperplasia and reduces vascular inﬂam- mation while allowing healing to occur. The second require- ment is for a stent design that permits homogenous delivery of optimal drug dosages using a system, which delivers the drug in a predictable fashion. The CYPHER SES brings together nearly ideal solutions that meet all three criteria. The unique combination of the highly effective anti-proliferative agent, sirolimus, a closed-cell design, and a biocompatible polymer results in exceptional outcomes. This combination of three elements produces optimal drug delivery; controlled, precise drug release; and marked reduction of late loss with a favorable safety proﬁle. Sirolimus – safety and tolerability Safety of a broad therapeutic window Sirolimus has been shown to have a broad therapeutic win- dow. In pre-clinical animal trials, sirolimus has demonstrated 196 Vascular Health and Risk Management 2007:3(2)