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 DS 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.
Departamento de Enfermedades Cardiovasculares, Pontificia Universidad Católica de Chile, Santiago, Chile. eguarda@med.puc.cl
Eduardo
E
Guarda
Eugenio
E
Marchant
Alejandro
A
Fajuri
Alejandro
A
Martínez
Sergio
S
Morán
Manuel
M
Mendez
Polentzi
P
Uriarte
Edith
E
Valenzuela
Rosa
R
Lazen
D000284:Administration, Oral; D000789:Angina, Unstable / Q000188:drug therapy / Q000628:therapy*; D015906:Angioplasty, Balloon, Coronary; D003131:Combined Modality Therapy; D017023:Coronary Angiography; D003327:Coronary Disease / Q000473:pathology / Q000628:therapy; D023903:Coronary Restenosis / Q000517:prevention & control*; D003331:Coronary Vessels / Q000473:pathology; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D010865:Pilot Projects; D020123:Sirolimus / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D015607:Stents; D017539:Tunica Intima / Q000187:drug effects
D007166:Immunosuppressive Agents; D020123:Sirolimus