title: Efficacy and safety of oral sirolimus to inhibit in-stent intimal hyperplasia.
abstract: Sirolimus systemic administration has shown marked inhibition of neointimal hyperplasia (NIH) after balloon angioplasty in porcine models. In this pilot study, we tested the hypothesis that oral sirolimus is safe and effective to inhibit in-stent NIH and therefore to prevent and treat in-stent restenosis (ISR). Twelve patients (18 lesions) with high risk for ISR, including 8 ISR lesions, were admitted. One day before the procedure, patients were given a 15 mg loading dose of oral sirolimus, followed by 5 mg daily for 28 days, with weekly whole blood level measurements. The daily dose was adjusted to keep the concentration at 10-15 ng/ml. Sirolimus was well tolerated by all patients but one, who died at the end of the third week of treatment. The 4- and 8-month follow-up revealed an angiographic late loss of 0.40 +/- 0.24 and 0.67 +/- 0.45 mm (P < 0.01), respectively. At the same time points, the intravascular ultrasound in in-stent relative volumetric obstruction was 14.4% +/- 9.1% and 23.2% +/- 10.1% (P < 0.01), respectively. At 24-month clinical follow-up, adverse events were one (8.3%) death, two (11.1%) target lesion, and four (22.2%) target vessel revascularizations. In conclusion, in this small group of high-risk ISR patients, oral sirolimus inhibited NIH and therefore may be an effective strategy for the prevention and treatment of ISR.
authors.affiliation: Hospital São Paulo and Hospital do Rim e Hipertensão, Federal University of São Paulo, Brazil.
authors.forename: Fábio S
authors.initials: FS
authors.lastname: Brito
authors.forename: Werther C M
authors.initials: WC
authors.lastname: Rosa
authors.forename: J Airton
authors.initials: JA
authors.lastname: Arruda
authors.forename: Hélio
authors.initials: H
authors.lastname: Tedesco
authors.forename: Jose O M
authors.initials: JO
authors.lastname: Pestana
authors.forename: Valter C
authors.initials: VC
authors.lastname: Lima
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D015906:Angioplasty, Balloon, Coronary / Q000009:adverse effects* / Q000379:methods; D017023:Coronary Angiography / Q000379:methods; D023903:Coronary Restenosis / Q000175:diagnosis / Q000188:drug therapy* / Q000517:prevention & control*; D023921:Coronary Stenosis / Q000175:diagnosis / Q000628:therapy*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011336:Probability; D018570:Risk Assessment; D012720:Severity of Illness Index; D020123:Sirolimus / Q000627:therapeutic use*; D018709:Statistics, Nonparametric; D015607:Stents / Q000009:adverse effects*; D016896:Treatment Outcome; D018084:Ultrasonography, Interventional; D014654:Vascular Patency / Q000187:drug effects
chemical_list: D020123:Sirolimus