Randomized, double-blind, placebo-controlled trial of oral sirolimus for restenosis prevention in patients with in-stent restenosis -: The oral sirolimus to inhibit recurrent in-stent stenosis (OSIRIS) trial
Randomized, double-blind, placebo-controlled trial of oral sirolimus for restenosis prevention in patients with in-stent restenosis -: The oral sirolimus to inhibit recurrent in-stent stenosis (OSIRIS) trial
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DOI：
10.1161/01.cir.0000138935.17503.35
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发表时间：
2004-08-17
期刊：
影响因子：
37.8
通讯作者：
Schömig, A
中科院分区：
文献类型：
--
作者：
Hausleiter, J;Kastrati, A;Schömig, A
背景-尽管介入心脏病学最近取得了进展，包括引入了药物洗脱支架来治疗新的冠状动脉病变，但支架内再狭窄(ISR)的治疗仍然是一个具有挑战性的临床问题。鉴于全身应用西罗莫司预防动物模型新生内膜增生和阻止甚至逆转移植物血管病变进展的有效性，本研究采用双盲、安慰剂对照研究，目的是评价两种不同负荷方案口服西罗莫司10天预防ISR患者复发再狭窄的效果。方法和结果：300名有症状的ISR患者随机分为3组：安慰剂、常规剂量或大剂量西罗莫司。患者在2天前和重复干预的前一天分别接受0、8或24 mg西罗莫司的累积负荷量，随后维持治疗2 mg/d，共7天。血管造影术后6个月的再狭窄是研究的主要终点。再狭窄发生率在安慰剂组为42.2%，常规剂量组为38.6%，大剂量组为22.1%(P=0.005)。同样，安慰剂组、普通剂量组和高剂量组靶血管再血管化的需要分别从25.5%降至24.2%和15.2%(P=0.08)。西罗莫司治疗当天血药浓度与术后晚期管腔丢失显著相关(P
Background-Despite recent advances in interventional cardiology, including the introduction of drug-eluting stents for de novo coronary lesions, the treatment of in-stent restenosis (ISR) remains a challenging clinical issue. Given the efficacy of systemic sirolimus administration to prevent neointimal hyperplasia in animal models and to halt and even reverse the progression of allograft vasculopathy, the aim of the present double-blind, placebo-controlled study was to evaluate the efficacy of a 10-day oral sirolimus treatment with 2 different loading regimens for the prevention of recurrent restenosis in patients with ISR.Methods and Results-Three hundred symptomatic patients with ISR were randomly assigned to 1 of 3 treatment arms: placebo or usual-dose or high-dose sirolimus. Patients received a cumulative loading dose of 0, 8, or 24 mg of sirolimus 2 days before and the day of repeat intervention followed by maintenance therapy of 2 mg/d for 7 days. Angiographic restenosis at 6-month angiography was the primary end point of the study. Restenosis was significantly reduced from 42.2% to 38.6% and to 22.1% in the placebo, usual-dose, and high-dose sirolimus groups, respectively (P=0.005). Similarly, the need for target vessel revascularization was reduced from 25.5% to 24.2% and to 15.2% in the placebo, usual-dose, and high-dose groups, respectively (P=0.08). The sirolimus blood concentration on the day of the procedure correlated significantly with the late lumen loss at follow-up (P