CLINICAL TRIALS
Oral rapamycin to inhibit restenosis after stenting of de novo coronary lesions
The Oral Rapamune to Inhibit Restenosis (ORBIT) study
Ron Waksman, MD*,*,
Andrew E. Ajani, MD ,
Augusto D. Pichard, MD*,
Rebecca Torguson, BS*,
Ellen Pinnow, MS*,
Daniel Canos, MPH*,
Lowell F. Satler, MD*,
Kenneth M. Kent, MD, PhD*,
Pramod Kuchulakanti, MD*,
Chrysoula Pappas, MD*,
Louise Gambone, RN*,
Neil Weissman, MD*,
Maureen C. Abbott, MS* and
Joseph Lindsay, MD*
*Cardiovascular Research Institute, Washington Hospital Center, Washington, DC
Royal Melbourne Hospital and NHMRC Centre of Clinical Research Excellence in Therapeutics, Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia
Manuscript received April 6, 2004;
revised manuscript received May 25, 2004,
accepted June 22, 2004.
* Reprint requests and correspondence: Dr. Ron Waksman, 110 Irving Street, NW, Suite 4B-1, Washington, DC 20010 (Email: ron.waksman{at}medstar.net).
OBJECTIVES: The aim of this study was to establish safety and feasibility of oral Rapamycin at two doses—2 mg and 5 mg—in achieving low rates of repeat target lesion revascularization (TLR) in de novo native coronary artery lesions.
BACKGROUND: Drug-eluting stents have shown the ability to limit restenosis. Oral Rapamycin is an alternative strategy that can target multiple coronary lesions suitable for treatment with any approved metal stent and at potentially lower cost.
METHODS: The Oral Rapamune to Inhibit Restenosis (ORBIT) study is an open-label study of 60 patients with de novo lesions treated with bare metal stents in up to two vessels. After a loading dose of 5 mg, patients received a daily dose of 2 mg (n = 30) and 5 mg (n = 30) for 30 days. Six-month angiographic, intravascular ultrasound (IVUS), and clinical follow-up were conducted.
RESULTS: Baseline clinical and procedural characteristics were similar: 10% of patients in the 2-mg group and 30% in the 5-mg group did not complete the course; 43% in the 2-mg group and 66% in the 5-mg group had side effects. At six-month follow-up, late loss (0.6 ± 0.5 mm vs. 0.7 ± 0.5 mm; p = NS), in-stent binary restenosis (7.1% vs. 6.9%; p = NS), in-stent percent volume obstruction by IVUS (29% vs. 24%; p = NS), and clinically driven TLR (14.3% vs. 6.9%; p = NS) were similar in 2-mg and 5-mg groups.
CONCLUSIONS: Oral Rapamycin for the prevention of restenosis is safe, feasible, and associated with low rates of repeat revascularization. Although associated with certain side effects, it may be considered for patients undergoing multivessel stents if proven in larger randomized studies.
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Abbreviations and Acronyms
| | CABG = coronary artery bypass graft surgery | | IVUS = intravascular ultrasound | | MI = myocardial infarction | | MLD = minimal luminal diameter | | ORAR = Oral Rapamycin to Prevent Restenosis in Patients Undergoing Coronary Stent Therapy trial | | ORBIT = Oral Rapamune to Inhibit Restenosis study | | OSIRIS = Oral Sirolimus to Inhibit Recurrent In-stent Stenosis trial | | PCI = percutaneous coronary intervention | | QCA = quantitative coronary angiography | | SMC = smooth muscle cell | | TLR = target lesion revascularization | | TVR = target vessel revascularization |
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