C vascular brachytherapy is, to date, the only effective treatment available for complex instent restenosis (ISR).1 However, its efficacy is hampered by late restenosis,2 late thrombosis,3,4 edge effect,5 geographic miss,6 and delayed healing.3 Moreover, the fate of the patients after “failed” brachytherapy is uncertain, as well as the result of the various percutaneous treatments employed thereafter. Sirolimus is a macrolide antibiotic produced by Streptomyces hygroscopicus with immunosuppressive effects; it is approved for the prevention of renal transplant rejection.7 The main effect of sirolimus is the interruption of G1 to S cell cycle progression mediated by its binding to a cytosolic receptor (FK506 protein binding protein 12) and a cascade of subsequent actions. Importantly, sirolimus inhibits proliferation and migration of vascular smooth muscle cells, a key element in the development of restenosis after percutaneous coronary interventions (PCIs). Recently, stent-based local sirolimus delivery has been shown to strongly suppress neointimal hyperplasia and prevent restenosis in de novo lesions followed up for 2 years.8,9 The revolutionary results obtained with drugeluting stents have encouraged the assessment of their efficacy in more complex clinical and morphologic subsets. The first human experience evaluating the sirolimus-eluting stent (SES) for the treatment of ISR has been recently reported; it showed this strategy to be highly effective.10 We describe here the first series of patients treated with SESs for recurrent ISR after brachytherapy. • • • The patients described in this report consist of 2 cohorts treated during separate time periods. The first cohort was treated between March 2001 and June 2001, as part of a pilot study on SESs for treatment of ISR. Since April 2002, shortly after European Community market approval, SES implantation has been adopted as the default strategy in all patients treated with PCI at our institution, irrespective of clinical presentation and coronary morphology. These latter patients have been included in the RESEARCH Registry (Rapamycin-Eluting Stent Evaluated At Rotterdam Cardiology Hospitals) and will be followed up for 1 year.11 The only exclusion criteria were unavailability of an adequately sized SES at the time of the procedure and enrollment in another revascularization protocol (SESs were available in diameters from 2.25 to 3.0 mm and lengths of 8, 18, and 33 mm). All patients treated with SES after “failed” brachytherapy were scheduled for 6-month angiography. ISR was defined as 50% diameter stenosis by quantitative coronary angiography within a previously stented vessel segment and classified as proposed by Mehran et al.12 Treatment strategy and device utilization other than stenting was left to the physician’s discretion. The procedure was considered successful when residual stenosis 30% by quantitative coronary angiography was achieved together with Thrombolysis In Myocardial Infarction (TIMI) flow grade 2 to 3. The study stent utilized was the sirolimus-eluting Cypher (Cordis Europa NV, Johnson & Johnson, Roden, The Netherlands), which contains a 140 g sirolimus/cm metal surface area in a slow release formulation ( 28 days). Pretreatment with clopidogrel for 48 hours or a 300-mg loading dose was required. During the procedure, intravenous heparin was given to maintain an activated clotting time 300 seconds. After the procedure, all patients received aspirin indefinitely ( 75 mg/day) and clopidogrel (75 mg/day) for at least 2 months. Clinical status information was collected at follow-up visits or by telephone contact with the patient or referring physician. Data are presented as number and relative percentage or mean SD. Median and range have been reported when deemed necessary for a better description. From the beginning of the study until August 15, 2002, 12 consecutive patients (both cohorts) underwent PCI with SES implantation for recurrent ISR after local radiation therapy. All of them presented with angina pectoris and/or myocardial ischemia as documented by stress test or thallium scan. Coronary brachytherapy had been previously performed in 11 patients with catheter-based local irradiation (10 beta, 1 gamma) and in 1 patient with phosphorus-32 radioactive stent implantation. Baseline clinical and angiographic characteristics are listed in Tables 1 and 2, respectively. Nine patients (75%) had had more than 1 previous episode of restenosis. Average time from the preceding percutaneous reintervention was 24 months (range 111 to 1,678 days, median 719). Remarkably, 9 patients (75%) presented with a From Erasmus MC, Thoraxcenter, Rotterdam, The Netherlands. Dr. Serruys’ address is: Erasmus MC, Thoraxcenter, Bd404, Dr. Molewaterplein 40, 3015 GD Rotterdam, The Netherlands. E-mail: p.w.j. c.serruys@erasmusmc.nl. Manuscript received January 16, 2003; revised manuscript received and accepted April 14, 2003.