冠心病合并肾功能不全患者两种支架植入的远期预后比较--I-LOVE-IT 2亚组研究

Long-term prognosis of patients with coronary heart disease and mild to moderate renal dysfunction after implantation of biodegradable polymer or durable polymer-coated drug-eluting stents——insight from the I-LOVE-IT 2 trial

目的比较冠心病合并不同程度肾功能不全患者植入新型生物可降解聚合物涂层西罗莫司洗脱支架(BP-SES)或永久涂层西罗莫司洗脱支架(DP-SES)后12个月的预后情况。方法选取I-LOVE-IT2研究中2603例植入支架患者,其中1744患者植入BP-SES,859例患者植入DP-SES,再按估算的肾小球滤过率(eGFR)不同分为不同的亚组,其中,BP-SES组分为肾功能正常组[eGFR≥90ml/(min.1.73m2),n=1136]、轻度肾功能不全组[90ml/(min.1.73m2)>eGFR≥60ml/(min.1.73m2),n=513]、中度肾功能不全组[60ml/(min.1.73m2)>eGFR≥30ml/(min.1.73m2),n=95],DPSES组分为肾功能正常组[eGFR≥90ml/(min.1.73m2),n=570]、轻度肾功能不全组[90ml/(min.1.73m2)>eGFR≥60ml/(min.1.73m2),n=254]、中度肾功能不全组[60ml/(min.1.73m2)>eGFR≥30ml/(min.1.73m2),n=35]。观察的主要研究终点为12个月靶病变失败率(TLF),包括心源性死亡、靶血管心肌梗死(TVMI)、临床驱动的靶病变血运重建(CI-TLR);次要终点为12个月净不良临床事件(NACCE),包括全因死亡、全部心肌梗死、缺血性卒中以及严重出血(BARC 3-5型)。结果 12个月临床随访结果显示,在植入BP-SES的患者中,3个亚组间主要终点指标TLF差异无统计学意义(6.2%vs.5.5%vs.8.5%,P=0.53),但中度肾功能不全组心源性死亡发生率明显高于其他两组(0.4%vs.0.2%vs.4.3%,P<0.01),各亚组间的CI-TLR(3.6%vs. 2.6%vs. 2.1%,P=0.46)及TVMI(3.3%vs. 3.9%vs. 5.4%,P=0.45)差异无统计学意义;而各亚组间的次要终点NACCE发生情况(6.4%vs. 6.2%vs. 13.7%,P=0.02)、BP-SES组不同肾功能不全患者的全因死亡(0.7%vs.0.9%vs.6.3%,P<0.01)、全部心肌梗死(1.1%vs.2.6%vs.4.4%,P=0.01)发生率差异均有统计学意义。在植入DP-SES的患者中,3个亚组间TLF(5.1%vs. 7.5%vs. 14.3%,P=0.05)、NACCE(6.8%vs. 6.3%vs. 17.1%,P=0.05)和TVMI(4.0%vs. 3.9%vs.14.3%,P=0.01)差异均有统计学意义,且中度肾功能不全患者事件发生率均最高。森林图显示植入BP-SES和DP-SES的不同程度肾功能不全患者,在各个观察终点上差异均无统计学意义。结论冠心病合并中度肾功能不全患者植入药物洗脱支架1年的死亡及心梗再发风险明显高于肾功能正常和轻度肾功能不全的患者,且冠心病合并不同程度肾功能不全患者中无论植入BP-SES还是DP-SES远期预后均无差异。

Objective To compare the prognosis of patients with coronary heart disease and different degrees of renal dysfunction after implantation of biodegradable polymer-coated sirolimus-eluting stents（BP-SES） or durable polymer-coated sirolimus-eluting stents（DP-SES）. Methods From the I-LOVE-IT2 study, 2603 patients [1744 were implanted with BP-SES and 859 with DP-SES] were divided into different subgroups according to the estimated glomerular filtration rate（eGFR）： in BPSES group, normal renal function subgroup（eGFR90 ml/（min.1.73 m^2）, n=1136）, mild renal insufficiency subgroup（90 ml/（min.1.73 m^2）eGFR60 ml/（min.1.73 m^2）, n=513）, and moderate renal insufficiency subgroup（60 ml/（min.1.73 m^2）eGFR30 ml/（min.1.73 m^2）, n=95）; in DP-SES group, normal renal function subgroup（eGFR90 ml/（min.1.73 m^2）, n=570）, mild renal insufficiency subgroup（90 ml/（min.1.73 m^2）eGFR60 ml/（min.1.73 m^2）, n=254）, and moderate renal insufficiency subgroup（60 ml/（min.1.73 m^2）eGFR30 ml/（min.1.73 m^2）, n=35）. The primary endpoint of the study was 12-month target lesion failure（TLF）, including cardiac death, target vascular myocardial infarction（TVMI）, and clinically indicated target lesion revascularization（CI-TLR）; the secondary endpoint was 12-months net adverse clinical and cerebral events（NACCE）, including all-causes of death, all myocardial infarction, stroke, and severe hemorrhage [bleeding academic research consortium（BARC 3-5）]. Results In BPSES group, clinical follow-up in 12 months indicated no significant difference in TLF among the three subgroups（6.2% vs. 5.5% vs. 8.5%, P=0.53）, but the incidence of cardiac death was higher in moderate renal insufficiency subgroup than in the other two subgroups（0.4% vs. 0.2% vs. 4.3%, P〈0.01）. No significant difference existed in the incidence of 12-month CI-TLR（3.6% vs. 2.6% vs. 2.1%, P=0.46） and TVMI（3.3% vs. 3.9% vs. 5.4%, P=0.45） among the 3 subgroups. The incidence of NACCE in the secondary endpoint was higher in moderate renal insufficiency subgroup（13.7%, P=0.02） than in normal renal function subgroup and mild renal insufficiency subgroup（6.2% vs. 6.4%, P=0.88）. Moreover, marked differences existed on all-cause mortality（0.7 % vs. 0.9% vs. 6.3%, P〈0.01） and all myocardial infarction（1.1% vs. 2.6% vs. 4.4%, P=0.01） among the 3 subgroups with BP-SES. In DP-SES group, significant difference existed on TLF（5.1% vs. 7.5% vs. 14.3%, P=0.05）, NACCE（6.8% vs. 6.3% vs. 17.1%, P=0.05） and TVMI（4.0% vs. 3.9% vs. 14.3%, P=0.01） among the 3 subgroups. Moreover, the incidence was highest in the moderate renal insufficiency subgroup. Forest plot indicated no difference existed between BP-SES and DP-SES group in different degrees renal dysfunction patients. Conclusions The risk of death and myocardial infarction significantly increased in patients with coronary heart disease and moderate renal insufficiency after implantation of drug-eluting stents than in those with normal renal function or mild renal insufficiency. No significant difference exists in the long-term prognosis of patients with different degrees of renal insufficiency after implantation of BP-SES or DP-SES.