Sirolimus-eluting coronary stents Figure 2 In higher risk cohorts, differences in late loss are more strongly associated with risk of target lesion revascularization. biological activity in doses ranging from 18 to 1200 µg without displaying toxicity to the vessel wall (Cordis Cor- poration, Warren, New Jersey, USA, data on ﬁle). • The highest dose now tested is approximately 6 times that of the CYPHER stent, with no adverse effects (no evidence of necrosis, aneurysm, or other pathology with 1200 µg in an exaggerated dose study. • The broad therapeutic proﬁle of sirolimus means that over- lapping stents can be deployed without the risk of toxicity due to overdosing (Suzuki et al 2001). SIRIUS data from over 27% of patients with 2 or more overlapping stents demonstrate the safety and efﬁcacy when overlapping SES (Moses et al 2003; Munoz et al 2004). Additional data come from the RESEARCH registry, based on a study population of patients who had a combination of ≥2 overlapping stents at a minimum length of 41 mm (ie, one 33 mm SES overlapping an 8 mm SES) to treat native de novo coronary lesions. The investigators monitored the incidence of major cardiac adverse events (death, non-fatal MI, and TLR). Clinical follow-up was available for all patients at a mean of 320 days (range 265–442). Angiographic follow-up at 6 months was obtained in 67 patients (71%). Binary restenosis rate was 11.9% and in-stent late loss was 0.13 +/– 0.47 mm. At long-term follow-up (mean 320 days), there were 2 deaths (2.1%), and the overall incidence of major cardiac events was 8.3%. The investigators concluded that SES implantation appears safe and effective for de novo coronary lesions requiring multiple stent placement over a very long vessel segment (Aoki et al 2005). • The ﬂat dose-response curve of sirolimus demonstrates a consistent, homogeneous anti-proliferative and anti-in- ﬂammatory effect at all doses evaluated, with no indication of cytotoxicity (Cordis Corporation, data on ﬁle). Stent thrombosis Since their introduction, more than 2 million patients, often with complex lesions, diabetes, and acute MI, have been treated with an SES. Although the published data support the claim that DES are safe and effective there have been concerns raised about the incidence of very late stent thrombosis (more than 1-year after implantation) compared with the use of bare metal stents (Iakovou et al 2005; Colombo and Corbett 2006). This concern has been fuelled by individual case reports and new long-term data from TAXUS-II, -IV, and -V and the Basel Stent Cost-Effectiveness Trial (BASKET) studies (American College of Cardiology Scientiﬁc Sessions 2006). However, despite these concerns over the long-term safety of DES, the actual incidence of stent thrombosis after 1-year is unknown (Park et al 2006). In the absence of an internationally accepted deﬁnition of late stent thrombosis or any fact-based evidence concerning the Vascular Health and Risk Management 2007:3(2) 197