Pilot study with an intensified oral sirolimus regimen for the prevention of in-stent restenosis in de novo lesions: a serial intravascular ultrasound study

This pilot study evaluated the safety and efficacy of an intensified oral sirolimus regimen (15-mg loading dose 24 hr before PCI, followed by a daily dose of 5 mg for 4 weeks) in 15 patients subjected to elective bare metal coronary stent implantation for de novo lesions. Mean patient age was 59 ± 9; 73% were male, and 13% were diabetic patients. The reference diameter was 3.04 ± 0.38 mm, and the lesion length was 14 ± 2 mm. Angiographic and volumetric intravascular ultrasound (IVUS) analyses were performed in all patients at 6.0 ± 0.2 months. Two patients (13%) met the definition of in-segment binary restenosis; in-stent and in-segment angiographic late loss was 0.61 ± 0.31 mm and 0.67 ± 0.45 mm, respectively, and the percent neointimal volume was 28.5 ± 15.8%. At adjacent reference segments, there was neither significant plaque increase nor constrictive vascular remodeling. At 24-month follow-up no deaths, myocardial infarctions, or target lesion revascularizations were detected. Mean sirolimus blood level was 13 ± 7 ng/ml. No correlations were found between drug levels and late loss (r = 0.15, P = 0.59) or IVUS percent neointimal volume (r = 0.23, P = 0.47). Side effects were frequent (80%), leading to dose reductions in four and drug discontinuation in one patient. The results of this pilot study suggest that an intensified 5-mg oral sirolimus regimen resulted in no relevant improvements in the angiographic and IVUS parameters of restenosis after stent implantation in de novo lesions when compared with historic controls. Considering the efficacy/safety balance, our results do not encourage further trials evaluating the current protocol for the prevention of in-stent restenosis. © 2005 Wiley-Liss, Inc.