Pilot study with an intensified oral sirolimus regimen for the prevention of in-stent restenosis in de novo lesions

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

patients. The reference diameter was 3.04 6 0.38 mm, and the lesion length was

14 6 2 mm. Angiographic and volumetric intravascular ultrasound (IVUS) analyses were

performed in all patients at 6.0 6 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 6

0.31 mm and 0.67 6 0.45 mm, respectively, and the percent neointimal volume was

infarctions, or target lesion revascularizations were detected. Mean sirolimus

blood level was 13 6 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

encourage further trials evaluating the current protocol for the prevention of in-stent

for de novo lesions. Mean patient age was 59 6 9; 73% were male, and 13% were diabetic

parameters of restenosis after stent implantation in de novo lesions when compared

with historic controls. Considering the efficacy/safety balance, our results do not

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.

Estudo piloto com administração de altas doses de sirolimus via oral pra prevenção de reestenose intra-stent em lesões de novo: avaliação seriada por meio do ultra-som intracoronário / Pilot study with high doses of oral sirolimus for preventing in-stent restenosis in de novo lesions: serial evaluation through intravascular ultrasound

Este estuo piloto avaliou a segurança e a eficácia do tratamento com altas doses de sirolimus por via oral (dose de 15mg, 24 horas antes da intervenção coronária percutânea, seguido por dose diária de 5 mg, durante quatro semanas) , em 15 pacientes submetidos a implante eletivo de stents metálicos convencionais em lesões de novo. A média de idade dos pacientes de estudo era de +- 59 anos, sendo 73% do sexo masculino e 13% diabéticos. O diâmetro de referência foi 3,04+- 0,38mm e a extensão da lesão 14+-2mm. A análise angiográfica e volumétrica por meio do ultra-som intravascular foi obtida em todos os pacientes aos 6,0+-0,2 meses. Dois (13%) pacientes apresentaram reestenose binária, com perda tardia intra-stent e intra-segmento de 0,61+-0,31mm e 0,67 +- 0,45mm, o volume da obstrução de neoíntima foi de 28,5+-15,8%.