From the Klinik für Innere Medizin III, Kardiologie, Angiologie und internistische Intensivmedizin, Universitätsklinikum des Saarlandes, Homburg/Saar, Germany (Y.P.C., S.B., B.C., M.B., B.S.); Institut für Radiologie, Charité-Universitätsmedizin Berlin, Campus Mitte, Humboldt Universität zu Berlin, Germany (D.P., B.K., U.S.); and B. Braun Melsungen AG, Berlin, Germany (J.C., M.-C.B., C.S., M.S.).
Circ Cardiovasc Interv. 2016 Apr;9(4):e003543. doi: 10.1161/CIRCINTERVENTIONS.115.003543.
Limus-eluting stents are dominating coronary interventions, although paclitaxel is the only drug on balloon catheters with proven inhibition of restenosis. Neointimal inhibition by limus-coated balloons has been shown in few animal studies, but data from randomized clinical trials are not available. The aim of the present preclinical studies was to achieve high and persistent sirolimus levels in the vessel wall after administration by a coated balloon.
Different coating formulations and doses were studied in the porcine coronary model to investigate sirolimus tissue levels at different time points as well as efficacy at 1 month using quantitative coronary angiography and histomorphometry. Loss of the selected coating in the valve, guiding catheter, and blood was low (2±14% of dose). Acute drug transfer to the vessel wall was 14.4±4.6% with the crystalline coating, whereas the amorphous coatings were less effective in this respect. Persistence of sirolimus in the vessel wall until 1 month was 40% to 50% of the transferred drug. At 1-month follow-up, a modest but significant reduction of neointimal growth was demonstrated in a dose range from 4 μg/mm(2) to 2×7 μg/mm(2), for example, maximum neointimal thickness of 0.38±0.13 versus 0.65±0.21 mm in the uncoated control group.
Various sirolimus-coated balloons effectively reduce neointimal proliferation in the porcine coronary model but differ considerably in retention time in the vessel wall. It has to be determined if such a formulation with persistent high vessel concentration will result in a relevant clinical effect.
雷帕霉素洗脱支架在冠状动脉介入治疗中占主导地位，尽管紫杉醇是唯一一种在球囊导管上应用的药物，可证实其能抑制再狭窄。已有少数动物研究显示雷帕霉素涂层球囊能抑制新生内膜增生，但尚未有随机临床试验的数据。本临床前研究的目的是在通过涂层球囊给药后使血管壁内获得高且持续的西罗莫司水平。
我们在猪冠状动脉模型中研究了不同的涂层配方和剂量，以在不同时间点检测组织中西罗莫司的浓度，并在 1 个月时通过定量冠状动脉造影和组织形态计量学评估疗效。选择的涂层在瓣膜、引导导管和血液中的损失较低（剂量的 2±14%）。结晶型涂层的急性药物向血管壁转移率为 14.4±4.6%，而无定形涂层在这方面效果较差。直到 1 个月时，药物在血管壁中的持续时间为转移药物的 40%至 50%。在 1 个月的随访中，在 4μg/mm2 至 2×7μg/mm2 的剂量范围内，观察到新生内膜生长有适度但显著的减少，例如，未涂层对照组的最大新生内膜厚度为 0.38±0.13mm，而涂层组为 0.65±0.21mm。
各种西罗莫司涂层球囊能有效减少猪冠状动脉模型中的新生内膜增生，但在血管壁中的保留时间差异很大。需要确定这种具有持续高血管浓度的制剂是否会产生相关的临床效果。
