Pilot trial of oral rapamycin for recalcitrant restenosis
Pilot trial of oral rapamycin for recalcitrant restenosis
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DOI：
10.1161/01.cir.0000066282.05411.17
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发表时间：
2003-04-08
期刊：
影响因子：
37.8
通讯作者：
Teirstein, PS
中科院分区：
文献类型：
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作者：
Brara, PS;Moussavian, M;Teirstein, PS
西罗莫司涂层支架是治疗再狭窄的一种有前景的新疗法。我们治疗了一组选择的患者在特别高的风险再狭窄与oral sirolimus.Methods和Results-Patients治疗与口服西罗莫司负荷剂量为6毫克冠状动脉成形术后，其次是2毫克/天4周。在开始给药后1、3和5周测量血清电解质、血脂、肾脏功能和全血细胞计数。口服西罗莫司处方给22例患者，他们总共有28处病变，并且有再狭窄的高风险。在22例研究患者中，11例（50%）因副作用或实验室异常而提前停用口服西罗莫司。高胆红素血症和白细胞减少症是最常见的不良事件，各有3例患者发生。停药后所有药物不良反应均可逆。100%的患者获得了平均9.9+/-1.8个月的随访，范围为6.5 - 11.8个月。靶病变血运重建（TLR）发生在15/28处病变（53.6%）和13/22例患者（59.1%）中。与提前终止治疗的患者（n=5; 45.5%; P=NS）相比，接受完整疗程西罗莫司的患者（n=8; 72.7%）的TLR无差异。15例（68.2%）患者接受了临床驱动的重复心导管检查; 13例（86.7%）患者出现了再狭窄（随访时直径狭窄>50%）。药物不良反应是常见的，强调了局部给药的重要性，以达到高组织浓度，而没有全身性的药物不良反应。
Background-Sirolimus-coated stents are a promising new therapy for restenosis. We treated a select group of patients at especially high risk for restenosis with oral sirolimus.Methods and Results-Patients were treated with an oral sirolimus-loading dose of 6 mg after coronary angioplasty, followed by 2 mg/d for 4 weeks. Serum electrolytes, lipid profile, renal panel, and complete blood cell count were measured at 1, 3, and 5 weeks after drug initiation. Oral sirolimus was prescribed to 22 patients who had a total of 28 lesions and were at high risk for restenosis. Of the 22 study patients, 11 (50%) discontinued oral sirolimus early because of side effects or laboratory abnormalities. Hypertriglyceridemia and leukopenia were the most frequent adverse events, occurring in 3 patients each. All adverse drug effects were reversible after discontinuation. Follow-up was obtained in 100% of patients at a mean of 9.9+/-1.8 months, ranging from 6.5 to 11.8 months. Target lesion revascularization (TLR) occurred in 15 of 28 lesions (53.6%) and 13 of 22 patients (59.1%). There was no difference in TLR for patients receiving a complete course of sirolimus (n=8; 72.7%) compared with patients who terminated treatment prematurely (n=5; 45.5%; P=NS). Clinically driven repeat cardiac catheterization was obtained in 15 (68.2%) patients; restenosis (>50% diameter stenosis at follow-up) was present in 13 (86.7%).Conclusion-Oral sirolimus does not appear to provide benefit to patients with recalcitrant restenosis. Adverse drug effects are frequent, underscoring the importance of local drug delivery to achieve high tissue concentrations without systemic adverse drug effects.