Oral rapamycin to prevent human coronary stent restenosis:: A pilot study

Background Recent human trials with rapamycin-eluting stents have shown very low restenosis rates. However, the high costs of these devices preclude their use in routine angioplasty, especially when considering multiple stenting. We evaluated whether orally administered rapamycin inhibits in-stent neointimal growth in patients with unstable angina. Methods We enrolled 15 patients successfully treated with the implantation of a single stent in a single de novo lesion in native coronary arteries. Correct stent expansion and apposition were corroborated with intravascular ultrasound scanning in all patients. Patients received aspirin, clopidogrel, and atorvastatin for 6 months. Rapamycin was administered in a loading dose of 5 mg, followed by 2 mg/day for 4 weeks. Results The reference diameter was 3.4 +/- 0.4 mm, lesion length was 11.2 +/- 2 mm, lesion type B1 was 36%, and lesion type B2 was 64%. After the procedure, in-stent minimal lumen diameter and diameter stenosis (DS) were 3.3 +/- 0.4 mm and 0.3% +/- 7.5%, respectively. At 10 days, plasma levels of rapamycin were 7.95 +/- 2.6 ng/mL. At 6 months, angiographic determinations demonstrated an in-stent minimal lumen diameter of 2 +/- 1 mm, an in-stent IDS of 41.3% 28.0%, and an in-stent late loss of 1.4 +/- 1.1 mm. Binary restenosis (>50% DS) was present in 6 of 15 patients (40%). Target lesion revascularization (coronary artery bypass grafting) was performed in 2 of 15 patients (13.3%). There were no serious adverse events during the 6-month period of follow-up, but 1 patient had severe heartburn caused by esophagitis, and another patient had herpes zoster at the end of the protocol. Conclusions Oral rapamycin was well tolerated, but did not suppress in-stent neointimal growth in this small group of patients.