血管内超声指导药物洗脱支架置入对合并慢性肾脏病患者长期预后的影响:ULTIMATE CKD亚组分析

Long-term outcomes of intravascular ultrasound-guided drug-eluting stent implantation in patients with chronic kidney disease:ULTIMATE CKD subgroup analysis

目的评估血管内超声(IVUS)指导药物洗脱支架(DES)置入对慢性肾脏病(CKD)患者长期临床结局的影响。方法研究对象来源于ULTIMATE研究,该研究是一项前瞻性、多中心、随机对照研究,从2014年8月到2017年5月在国内8家中心入选1448例置入DES的冠心病患者,按1∶1的比例随机分为两组(接受IVUS或冠状动脉造影指导支架置入)。本研究选取ULTIMATE研究中有基线血肌酐值的患者1443例,分为CKD组和非CKD组。CKD的定义为Cockcroft-Gault(CG)公式得出的估算的肾小球滤过率(eGFR)<60 ml·min^(-1)·1.73 m^(-2)至少3个月。主要终点是术后3年靶血管失败(TVF),包含心原性死亡、靶血管心肌梗死和临床症状驱动的靶血管血运重建。采用Kaplan-Meier法进行生存分析,通过log-rank检验比较各组的终点事件发生情况,并采用Cox风险比例模型计算HR及其95%CI,同时检验交互作用。采用多因素Cox回归分析TVF的独立影响因素。结果本研究共入选1443例置入DES的冠心病患者,其中CKD组349例(24.2%),非CKD组1094例。CKD组中采用IVUS指导支架置入者180例,造影指导支架置入者169例;非CKD组中采用IVUS指导支架置入者543例,造影指导支架置入者551例。3年临床随访率为98.3%(1418/1443)。术后3年时,CKD组的TVF发生率为12.0%(42/349),高于非CKD组的7.4%(81/1094)(P=0.01),其差异主要来源于CKD组更高的心原性死亡率[4.6%(16/349)比1.5%(16/1094),P<0.001]。CKD组中IVUS指导下置入支架者的TVF发生率低于造影指导下置入支架者[8.3%(15/180)比16.0%(27/169),P=0.03]。而非CKD组共81例发生TVF,其中IVUS指导下置入支架者的TVF发生率与造影指导下置入支架者差异无统计学意义[5.9%(32/543)比8.9%(49/551),P=0.06],不存在交互作用(P=0.47)。多因素Cox回归分析结果显示,IVUS指导(HR=0.56,95%CI 0.39~0.81,P=0.002)、CKD(HR=1.83,95%CI 1.17~2.87,P=0.010)和支架长度(每增加10 mm)(HR=1.11,95%CI 1.04~1.19,P=0.002)是置入DES术后3年发生TVF的独立影响因素。结论对于置入DES的冠心病患者,合并CKD者术后3年的TVF发生风险高于非CKD患者;相比于冠状动脉造影,IVUS指导DES置入可以降低CKD患者的TVF风险。

Objective To explore the long-term effect of intravascular ultrasound(IVUS)guidance on patients with chronic kidney disease(CKD)undergoing drug-eluting stent(DES)implantation.Methods Data used in this study derived from ULTIMATE trial,which was a prospective,multicenter,randomized study.From August 2014 to May 2017,1448 patients with coronary heart disease undergoing DES implantation were selected from 8 domestic centers and randomly divided into two groups in the ratio of 1∶1(IVUS or coronary angiography guided stent implantation).A total of 1443 patients with the baseline serum creatine available were enrolled.The patients were divided into CKD group and non CKD group.CKD was defined as the estimated glomerular filtration rate(eGFR)derived from Cockcroft Gault(CG)formula<60 ml·min^(-1)·1.73 m^(-2) for at least 3 months.Primary endpoint of this study was target vessel failure(TVF)at 3 years,including cardiac death,target vessel myocardial infarction,and clinically-driven target vessel revascularization.Kaplan Meier method was used for survival analysis,and log rank test was used to compare the occurrence of end-point events in each group.Cox proportional hazards model was used to calculate HR and 95%CI,and interaction was tested.Multivariate Cox regression was used to analyze the independent influencing factors of TVF.Results A total of 1443 patients with coronary heart disease were enrolled in this study,including 349(24.2%)patients in CKD group and 1094 patients in non CKD group.In CKD group,IVUS was used to guide stent implantation in 180 cases and angiography was used in 169 cases;in non CKD group,IVUS was used to guide stent implantation in 543 cases and angiography was used in 551 cases.Three-year clinical follow-up was available in 1418 patients(98.3%).The incidence of TVF in CKD group was 12.0%(42/349),which was higher than that in non CKD group(7.4%(81/1094)(P=0.01).The difference was mainly due to the higher cardiac mortality in CKD group(4.6%(16/349)vs.1.5%(16/1094),P<0.001).In CKD group,the incidence of TVF in patients who underwent IVUS guided stent implantation was lower than that in angiography guided stent implantation(8.3%(15/180)vs.16.0%(27/169),P=0.03).There was no significant difference in the incidence of TVF between IVUS guided stent implantation and angiography guided stent implantation in non CKD group(5.9%(32/543)vs.8.9%(49/551),P=0.06),and there was no interaction(P=0.47).Multivariate Cox regression analysis showed that IVUS guidance(HR=0.56,95%CI 0.39-0.81,P=0.002),CKD(HR=1.83,95%CI 1.17-2.87,P=0.010)and stent length(every 10 mm increase)(HR=1.11,95%CI 1.04-1.19,P=0.002)were independent risk factors for TVF within 3 years after DES implantation.Conclusions CKD patients undergoing DES implantation are associated with a higher risk of 3-year TVF.More importantly,the risk of TVF could be significantly decreased through IVUS guidance in comparison with angiography guidance in patients with CKD.