金怡婧,施秋萍,张斌,李锴印,郑博,陈明,王新刚

• 1:北京大学第一医院心血管内科
• 2:北京大学第一医院心血管研究所

摘要(Abstract)：

目的 本临床前研究借助小型猪冠状动脉模型，通过与SeQuent Please药物涂层球囊（SQP）对比，评估新型自动灌注药物涂层球囊（ADCB）的有效性及安全性。方法 共对21头小型猪进行2支冠状动脉的支架置入+药物涂层球囊扩张成形术，每头小型猪置入2枚支架，累计42条冠状动脉完成支架置入，因1例动物术后早期死亡，最终20头小型猪的40条冠状动脉完成术后随访及取样。每头小型猪ADCB和SQP按1﹕1应用，随机分配于靶血管中。术后第14天、第28天及第90天进行随访评估，包括定量冠状动脉造影、组织病理学评估，以及紫杉醇药物球囊残留与组织浓度分析。结果 除1头小型猪因术后1 h内发生支架移位导致死亡，其余20头均完成研究。术后第14天时，ADCB组与SQP组相比，晚期管腔丢失显著减少[（0.00±0.11）mm比（0.15±0.09）mm,P=0.046]，差异有统计学意义；狭窄百分比亦呈现降低趋势[（0.02±5.08）%比（6.54±4.54）%,P=0.051]，但差异无统计学意义。在术后第28天及第90天时，两组血管造影结果比较，差异均无统计学意义（均P>0.05）。组织病理学分析显示，两组新生内膜形成、炎症评分及血管损伤程度相当，差异均无统计学意义（均P>0.05）。尽管早期时间点两组药物残留量（第14天P=0.126；第28天P=0.140）差异均无统计学意义，但ADCB组在第90天时血管壁紫杉醇残留浓度显著更高[（0.03±0.03）μg/g比（0.01±0.01）μg/g,P=0.048]，差异有统计学意义。两组安全性结果相当，均未发生支架内血栓形成或手术并发症。结论 在90 d随访期间，ADCB的有效性及安全性均不劣于SQP。

关键词(KeyWords)： 冠心病;经皮冠状动脉介入治疗;动物模型;药物涂层球囊;自动灌注技术

Abstract:

Keywords:

基金项目(Foundation):

作者(Author): 金怡婧,施秋萍,张斌,李锴印,郑博,陈明,王新刚

参考文献(References)：

• [1]Gruntzig A. Transluminal dilatation of coronary-artery stenosis[J]. Lancet, 1978, 1(8058):263. DOI:10.1016/s0140-6736(78)90500-7.
• [2]Byrne RA,Stone GW,Ormiston J,et al. Coronary balloon angioplasty, stents, and scaffolds[J]. Lancet,2017,390(10096):781-792. DOI:10.1016/S0140-6736(17)31927-X.
• [3]郝伟，赵晨，胡思宁，等.冠状动脉药物洗脱支架内再狭窄的最新研究进展[J].中国介入心脏病学杂志，2023,31(1):63-68. DOI:10.3969/j.issn.1004-8812.2023.01.010.
• [4]Neumann FJ, Sousa-Uva M, Ahlsson A, et al. 2018 ESC/EACTS Guidelines on myocardial revascularization[J]. Eur Heart J, 2019, 40(2):87-165. DOI:10.1093/eurheartj/ehy394.
• [5]Jinnouchi H, Torii S, Sakamoto A, et al. Fully bioresorbable vascular scaffolds:lessons learned and future directions[J].Nat Rev Cardiol, 2019, 16(5):286-304. DOI:10.1038/s41569-018-0124-7.
• [6]《药物涂层球囊临床应用中国专家共识（第二版）》专家组.药物涂层球囊临床应用中国专家共识（第二版）[J].中国介入心脏病学杂志，2023,31(6):413-426. DOI:10.3969/j.issn.1004-8812.2023.06.003.
• [7]Scheller B, Hehrlein C, Bocksch W, et al. Treatment of coronary in-stent restenosis with a paclitaxel-coated balloon catheter[J]. N Engl J Med, 2006, 355(20):2113-2124.DOI:10.1056/NEJMoa061254.
• [8]Jeger RV, Farah A, Ohlow MA, et al. Drug-coated balloons for small coronary artery disease(BASKET-SMALL 2):an openlabel randomised non-inferiority trial[J]. Lancet, 2018, 392(10150):849-856. DOI:10.1016/S0140-6736(18)31719-7.
• [9]Tang Y, Qiao S, Su X, et al. Drug-coated balloon versus drug-eluting stent for small-vessel disease:the RESTORE SVD China randomized trial[J]. JACC Cardiovasc Interv, 2018,11(23):2381-2392. DOI:10.1016/j.jcin.2018.09.009.
• [10]Kleber FX, Rittger H, Ludwig J, et al. Drug eluting balloons as stand alone procedure for coronary bifurcational lesions:results of the randomized multicenter PEPCAD-BIF trial[J].Clin Res Cardiol, 2016, 105(7):613-621. DOI:10.1007/s00392-015-0957-6.
• [11]Shin ES, Ann SH, Balbir Singh G, et al. Fractional flow reserve-guided paclitaxel-coated balloon treatment for de novo coronary lesions[J]. Catheter Cardiovasc Interv, 2016, 88(2):193-200. DOI:10.1002/ccd.26257.
• [12]Rissanen TT, Uskela S, Er??nen J, et al. Drug-coated balloon for treatment of de-novo coronary artery lesions in patients with high bleeding risk(DEBUT):a single-blind, randomised,non-inferiority trial[J]. Lancet, 2019, 394(10194):230-239. DOI:10.1016/S0140-6736(19)31126-2.
• [13]Camaj A, Leone PP, Colombo A, et al. Drug-coated balloons for the treatment of coronary artery disease:a review[J]. JAMA Cardiol, 2025, 10(2):189-198. DOI:10.1001/jamacardio.2024.4244.
• [14]Merinopoulos I,Gunawardena T,Corballis N,et al. Paclitaxel drug-coated balloon-only angioplasty for de novo coronary artery disease in elective clinical practice[J]. Clin Res Cardiol, 2023,112(9):1186-1193. DOI:10.1007/s00392-022-02106-y.
• [15]Merinopoulos I, Gunawardena T, Corballis N, et a l. Assessment of paclitaxel drug-coated balloon only angioplasty in STEMI[J]. JACC Cardiovasc Interv, 2023, 16(7):771-779. DOI:10.1016/j.jcin.2023.01.380.
• [16]Kleber FX, Rittger H, Bonaventura K, et al. Drug-coated balloons for treatment of coronary artery disease:updated recommendations from a consensus group[J]. Clin Res Cardiol,2013, 102(11):785-797. DOI:10.1007/s00392-013-0609-7.
• [17]Rhee TM, Lee JM, Shin E-S, et al. Impact of optimized procedure-related factors in drug-eluting balloon angioplasty for treatment of in-stent restenosis[J]. JACC Cardiovasc Interv,2018, 11(10):969-978. DOI:10.1016/j.jcin.2018.02.002.
• [18]Turi ZG, Campbell CA, Gottimukkala MV, et al. Preservation of distal coronary perfusion during prolonged balloon inflation with an autoperfusion angioplasty catheter[J]. Circulation, 1987,75(6):1273-1280. DOI:10.1161/01.cir.75.6.1273.
• [19]Dorros G,Cowley MJ,Simpson J,et al. Percutaneous transluminal coronary angioplasty:report of complications from the national heart,lung,and blood institute PTCA registry[J]. Circulation,1983,67(4):723-730. DOI:10.1161/01.cir.67.4.723.
• [20]Cai X, Zhou S, Cai X, et al. Comparing the efficacy and safety of two different drug-coated balloons in in-stent restenosis:two-year clinical outcomes of the RESTORE ISR China randomized trial[J]. J Cardiol, 2023, 81(1):76-82. DOI:10.1016/j.jjcc.2022.08.014.
• [21]Schwartz RS, Huber KC, Murphy JG, et al. Restenosis and the proportional neointimal response to coronary artery injury:results in a porcine model[J]. J Am Coll Cardiol, 1992, 19(2):267-274. DOI:10.1016/0735-1097(92)90476-4.
• [22]Kornowski R, Hong MK, Tio FO, et al. In-stent restenosis:contributions of inflammatory responses and arterial injury to neointimal hyperplasia[J]. J Am Coll Cardiol, 1998, 31(1):224-230. DOI:10.1016/s0735-1097(97)00450-6.
• [23]Katsanos K, Spiliopoulos S, Kitrou P, et al. Risk of death following application of paclitaxel-coated balloons and stents in the femoropopliteal artery of the leg:a systematic review and metaanalysis of randomized controlled trials[J]. J Am Heart Assoc,2018, 7(24):e011245. DOI:10.1161/JAHA.118.011245.
• [24]Dan K, Shlofmitz E, Khalid N, et al. Paclitaxel-related balloons and stents for the treatment of peripheral artery disease:insights from the food and drug administration 2019 circulatory system devices panel meeting on late mortality[J]. Am Heart J, 2020, 222:112-120. DOI:10.1016/j.ahj.2019.12.012.
• [25]Cremers B, Speck U, Kaufels N, et al. Drug-eluting balloon:very short-term exposure and overlapping[J]. Thromb Haemost,2009, 101(1):201-206. DOI:10.1160/TH08-06-0387.
• [26]Tzafriri AR, Garcia-Polite F, Zani B, et al. Calcified plaque modification alters local drug delivery in the treatment of peripheral atherosclerosis[J]. J Control Release, 2017,264:203-210. DOI:10.1016/j.jconrel.2017.08.037.