吲哚布芬与阿司匹林预防冠状动脉旁路移植术后桥血管再狭窄的随机对照试验

A randomized controlled trial of indobufen versus aspirin in the prevention of bridging restenosis after coronary artery bypass grafting

目的对比吲哚布芬与阿司匹林预防非体外循环下冠状动脉旁路移植术后1年桥血管再狭窄的有效性及安全性。方法本研究为前瞻性队列研究,选取2016年12月—2018年12月北京安贞医院收治的152例接受冠状动脉旁路移植术治疗的患者,根据术后抗血小板方案分为吲哚布芬组及阿司匹林组。吲哚布芬组患者术后接受吲哚布芬及氯吡格雷治疗,阿司匹林组患者术后接受阿司匹林及氯吡格雷治疗。收集两组患者的年龄、性别等基本临床资料。术后随访1年,比较两组患者术后1年大隐静脉桥血管及乳内动脉桥血管再狭窄的发生情况、心脏不良事件发生情况及不良反应发生情况;比较两组患者冠状动脉旁路移植术前及术后1年凝血指标纤维蛋白原(FIB)、D-二聚体(D-D)、血清血栓调节蛋白(TM)及凝血酶激活纤溶抑制物(TAFI)水平。结果吲哚布芬组76例,男性57例(75.0%),年龄(60.3±6.6)岁;阿司匹林组76例,男性62例(81.6%),年龄(59.7±7.2)岁,两组基线资料比较差异无统计学意义(P均>0.05)。随访期间失访3例,吲哚布芬组完成随访的有74例,阿司匹林组75例。吲哚布芬组共移植268条桥血管,阿司匹林组共移植272条。术后1年,吲哚布芬组大隐静脉桥血管及乳内动脉桥血管通畅率分别为94.5%(189/200)和97.1%(66/68),阿司匹林组大隐静脉桥血管及乳内动脉桥血管通畅率分别为91.3%(189/207)和96.9%(63/65);两组大隐静脉桥血管及乳内动脉桥血管通畅率相比较差异无统计学意义(χ^(2)=0.282、0.345,P>0.05)。吲哚布芬组和阿司匹林组心脏不良事件总发生率分别为5.4%(4/74)和6.7%(5/75),差异无统计学意义(χ^(2)=0.126,P>0.05)。吲哚布芬组术后1年胃肠道不良反应总发生率为4.1%(3/74),低于阿司匹林组的13.3%(10/75),差异有统计学意义(χ^(2)=4.547,P<0.05)。两组患者FIB、D-D、TM及TAFI水平均低于术前(P<0.05),术前及术后组间比较差异均无统计学意义(P>0.05)。结论吲哚布芬与氯吡格雷联用预防冠状动脉旁路移植术后1年桥血管再狭窄的疗效与阿司匹林与氯吡格雷联用基本相当,且吲哚布芬引起的胃肠道不良反应发生率相对较低,安全性可能更高。

Objective To compare the efficacy and safety between indobufen and aspirin in the prevention of restenosis of bridge vessels at 1 year after off-pump coronary artery bypass grafting.Methods This study was a prospective cohort study.We selected 152 patients who received coronary artery bypass grafting in Beijing Anzhen Hospital from December 2016 to December 2018.Patients were divided into the indobufen group and the aspirin group.Patients in the aspirin group were treated with aspirin and clopidogrel,and patients in the indobufen group were treated with indobufen and clopidogrel.During the 1-year follow-up,the rate of restenosis of saphenous vein bridge and internal mammary artery bridge,the rate of adverse cardiac events and adverse reactions were compared between the two groups.The levels of fibrinogen(FIB),D-dimer(D-D),thrombomodulin(TM)and thrombin-activatable fibrinolysis inhibitor(TAFI)were compared before and after antiplatelet therapy.Results There were 76 cases in the indobufen group,including 57 males(75.0%),aged(60.3±6.6)years.There were 76 cases in the aspirin group,including 62 males(81.6%),aged(59.7±7.2)years.Baseline data were comparable between the two groups(P>0.05).During the follow-up,3 cases were lost to follow up.Follow-up was completed in 74 patients in the indobufen group and 75 in the aspirin group.A total of 268 bridging vessels were grafted in the indobufen group and 272 in the aspirin group.One year after surgery,the patency rates of great saphenous vein bridge and internal mammary artery bridge were 94.5%(189/200)and 97.1%(66/68)in the indobuphen group,and 91.3%(189/207)and 96.9%(63/65)in the aspirin group,respectively.There was no significant difference in patency rate of great saphenous vein bridge and internal mammary artery bridge between the two groups(χ^(2)=0.282,0.345,P>0.05).The total incidence of adverse cardiac events was 5.4%(4/74)in the indobufen group and 6.7%(5/75)in the aspirin group(χ^(2)=0.126,P>0.05).The overall incidence of gastrointestinal adverse reactions was significantly lower in the indobufen group than in the aspirin group(4.1%(3/74)vs.13.3%(10/75),χ^(2)=4.547,P<0.05).The levels of FIB,D-D,TM and TAFI in the two groups were lower than those before surgery(P<0.05),and there was no statistical significance between the two groups at baseline and post-operation(P>0.05).Conclusion The efficacy of indobufen combined with clopidogrel in the prevention of 1-year restenosis after coronary artery bypass graft is similar to that of aspirin combined with clopidogrel,but the incidence of adverse reactions is lower,and the safety is higher in patients treated with indobufen combined with clopidogrel compared to aspirin combined with clopidogrel strategy.