Meneveau N, Schiele F, Grollier G, Farah B, Lablanche J M, Khalifé K, Machecourt J, Danchin N, Wolf J E, Simpson M, Hak J B, Bassand J P
Hôpital Jean-Minjoz, Besançon, France.
Eur Heart J. 2000 Nov;21(21):1767-75. doi: 10.1053/euhj.1999.2041.
We hypothesized that intramural delivery of nadroparin, a low molecular weight heparin, would prevent in-stent restenosis by inhibiting neointimal hyperplasia in an angioplasty model free of arterial remodelling.
In a prospective randomized multicentre trial, 250 patients submitted to balloon angioplasty followed by stent implantation were randomized into control group (no local drug delivery) or intramural delivery of nadroparin (2 ml of 2500 anti-Xa-units/ml with a microporous catheter). An ancillary intravascular ultrasound substudy was performed to supplement angiographic data with specific measurements of in-stent neointimal hyperplasia. The primary end-point was the late loss in minimal luminal diameter on the 6 month follow-up angiogram. Secondary end-points included feasibility and safety of local nadroparin delivery, and major adverse cardiac events at 8 weeks and 6 months follow-up. Local delivery of nadroparin was successful in 124 patients (99.2% success rate) and was not associated with an increase in stent thrombosis, coronary artery dissection, side branch occlusion, distal embolization or abrupt arterial closure. At angiographic follow-up, the late loss in lumen diameter was 0.84 +/- 0.62 mm in the control group compared to 0.88 +/- 0.63 mm in the nadroparin group (P=0.56). Angiographic restenosis rate (defined as a >50% diameter stenosis) did not differ in the control group (20%) compared to the nadroparin group (24%). The average area of neointimal tissue within the stent was 2.86 +/- 0.64 mm(2) vs 2.90 +/- 0.53 mm(2) (P=0.57), control vs nadroparin groups. There was no difference in major adverse cardiac events at any time (88.8% vs 89.6% event free survival at 6 months, control vs nadroparin).
Intramural delivery of nadroparin with a microporous catheter after stent deployment was feasible and safe but had no effect in reducing restenosis or the occurrence of major adverse clinical events over 6 months.
我们假设，在无动脉重塑的血管成形术模型中，通过抑制新生内膜增生，低分子量肝素那屈肝素的壁内给药可预防支架内再狭窄。
在一项前瞻性随机多中心试验中，250例行球囊血管成形术并随后植入支架的患者被随机分为对照组（未进行局部药物递送）或那屈肝素壁内给药组（使用微孔导管给予2 ml 2500抗Xa单位/毫升的药物）。进行了一项辅助血管内超声子研究，以通过对支架内新生内膜增生的特定测量来补充血管造影数据。主要终点是6个月随访血管造影时最小管腔直径的晚期丢失。次要终点包括那屈肝素局部递送的可行性和安全性，以及8周和6个月随访时的主要不良心脏事件。那屈肝素局部递送在124例患者中成功（成功率99.2%），且与支架血栓形成、冠状动脉夹层、侧支闭塞、远端栓塞或动脉突然闭塞的增加无关。在血管造影随访时，对照组管腔直径的晚期丢失为0.84±0.62 mm，那屈肝素组为0.88±0.63 mm（P = 0.56）。对照组的血管造影再狭窄率（定义为直径狭窄>50%）为20%，那屈肝素组为24%，两组无差异。支架内新生内膜组织的平均面积，对照组为2.86±0.64 mm²，那屈肝素组为2.90±0.53 mm²（P = 0.57）。在任何时间点，主要不良心脏事件均无差异（6个月时无事件生存率，对照组为88.8%，那屈肝素组为89.6%）。
支架置入后使用微孔导管进行那屈肝素壁内给药是可行且安全的，但在6个月内对减少再狭窄或主要不良临床事件的发生没有效果。
