Five-Year Clinical Outcomes of Sirolimus-Eluting Versus Paclitaxel-Eluting Stents in High-Risk Patients K. Anette Birkmeier, 1 * MD, Adnan Kastrati, 1 MD, Robert A. Byrne, 1 MB, MRCPI, Heidrun Holle, 1 Stefanie Schulz, 1 MD, Klaus Tiroch, 1 MD, Sebastian Kufner, 1 MD, Steffen Massberg, 1 MD, Karl-Ludwig Laugwitz, 2 MD, Albert Scho ¨ mig, 2 MD, and Julinda Mehilli, 1 MD Objectives and Background: First generation drug-eluting stents have shown differential efficacy in high-risk patient subsets at one year. It is unclear whether these differences endure over the medium- to long-term. We compared the five-year clinical efficacy and safety of sirolimus-eluting stents (SES) and paclitaxel-eluting stents (PES) in a popula- tion of high-risk patients. Methods: The patient cohorts of the ISAR-DESIRE, ISAR-DIA- BETES, and ISAR-SMART-3 randomized trials were followed up for five years and data were pooled. The primary efficacy endpoint of the analysis was the need for target lesion revascularization (TLR) during a five-year follow-up period. The primary safety endpoint was the combination of death or myocardial infarction (MI) after five years. Results: A total of 810 patients (405 patients in the SES group and 405 patients in the PES group) was included. Over five years TLR was reduced by 39% with SES compared with PES stent (hazard ratio [HR] 0.61; 95% confidence interval [CI] 0.44–0.85; P 5 0.004). No dif- ference was observed according to death or MI rates between the two groups (HR 1.10; 95% CI 0.80–1.50; P 5 0.57). Definite stent thrombosis occurred in 0.2% (n 5 1) in the SES group and in 1.6% (n 5 6) in the PES group (HR 0.16; 95% CI 0.02–1.34; P 5 0.12). Conclusions: In high-risk patient subsets the lower rate of 12-month TLR observed with SES in comparison PES is maintained out to five years. In terms of safety, although there was no difference in the overall incidence of death or MI, there was a trend towards more frequent stent thromboses with PES. V C 2011 Wiley-Liss, Inc. Key words: drug-eluting stent; long-term outcome; paclitaxel; sirolimus; stent thrombosis; target lesion revascularization INTRODUCTION The long-term therapeutic superiority of first genera- tion drug-eluting stents (DES) over bare-metal stents in terms of clinical antirestenotic efficacy has been well established by a series of randomized controlled trials [1–5]. However, it is increasingly recognized that by virtue of their mechanism of action, DES are associ- ated with systematic delayed healing of the stented ar- terial segment [6–8]. This process likely underlies the slight excess of late stent thrombosis events observed after DES implantation in comparison with bare metal stent therapy [3,4]. In addition, this delay in healing shifts the time course of endothelial regrowth, neointi- mal formation and angiographic restenosis beyond the six to eight month time window typically considered appropriate for evaluation of device performance in the era of bare metal stent interventions [9]. Significant differences exist between the sirolimus- eluting stent (SES) and paclitaxel-eluting stent (PES) with respect to the bare-metal stent platform, perma- nent polymer and antiproliferative drug used [10]. In high-risk groups, SES were shown to have superior anti- restenotic efficacy to PES in a number of randomized controlled trials [11–16]. In particular, the ISAR- DESIRE (Intracoronary Stenting and Angiographic Results-Drug-Eluting Stents for In-Stent-Restenosis) trial [11], the ISAR-DIABETES trial [12], and the ISAR-SMART-3 (Intracoronary Stenting or Angioplasty for Restenosis Reduction in Small Arteries) trial [13] 1 Deutsches Herzzentrum, Technische Universita ¨ t, Munich 2 1. Medizinische Klinik, Klinikum rechts der Isar, Technische Universita ¨ t, Munich Conflict of interest: Nothing to report. *Correspondence to: K. Anette Birkmeier, MD, ISAResearch Center, Deutsches Herzzentrum, Lazarettstrasse 36, 80636 Munich, Germany. E-mail: birkmeier@dhm.mhn.de Received 2 June 2010; Revision accepted 21 July 2010 DOI 10.1002/ccd.22757 Published online 15 February 2011 in Wiley Online Library (wileyonlinelibrary.com) V C 2011 Wiley-Liss, Inc. Catheterization and Cardiovascular Interventions 77:494–501 (2011)