高剂量替罗非班在急性ST段抬高型心肌梗死患者直接经皮冠状动脉介入术中的安全性及有效性评价

摘要

目的：探讨高剂量替罗非班在急性 ST 段抬高型心肌梗死（ STEMI ）患者直接经皮冠状动脉介入（ PPCI）术中的安全性及有效性。方法连续收集2010年1月—2011年2月因急性STEMI于首都医科大学附属北京天坛医院行PPCI术的患者134例为研究对象。按照随机数字表法将患者平均分为标准剂量组（在3 min内静脉注射替罗非班弹丸10μg/kg，随后以0.150μg·kg-1·min-1持续静脉泵入）和高剂量组（静脉注射替罗非班弹丸20μg/kg，随后以0.225μg·kg-1·min-1持续静脉泵入），各67例。记录心肌梗死溶栓试验（ TIMI）血流分级、超声心动图检查结果及术后90 min ST段抬高回落百分比（ STR）；记录住院期间和出院90 d内安全性终点（包括大出血、出血性卒中、血小板减少）和有效性终点即主要不良心脏事件（ MACE）（包括死亡、再梗死、急性靶血管再次血运重建）。结果两组患者一般资料比较，差异均无统计学意义（P>0.05）。两组患者冠状动脉病变支数、梗死相关血管（IRA）、支架直径、支架长度、支架数量、未成功的PPCI术、术前TIMI血流分级、普通肝素、低分子肝素、血管紧张素转换酶抑制剂（ACEI）/血管紧张素受体阻断剂（ARB）、β受体阻滞剂、他汀类药物比较，差异均无统计学意义（P>0.05）；高剂量组术后TIMI血流分级3级发生率高于标准剂量组（χ2=7.309，P=0.007）。术后90 d两组患者舒张末期室间隔厚度（IVST）、舒张末期左心室后壁厚度（ LVPWT）、左心室舒张末期内径（ LVEDD）、左心室收缩末期内径（LVESD）比较，差异无统计学意义（P>0.05）；高剂量组术后90 d左心室射血分数（LVEF）高于标准剂量组（P<0.05）。术后90 d标准剂量组、高剂量组LVPWT、LVEDD、LVESD、LVEF与入院当日比较，差异均有统计学意义（ P<0.05）。高剂量组术后90 min STR高于标准剂量组（t=-3.678，P<0.05）。高剂量组完全回落率高于标准剂量组，部分回落率低于标准剂量组（χ2=9.046、6.351，P=0.003、0.012）；两组未回落率比较，差异无统计学意义（χ2=1.729，P=0.189）。住院期间及出院90 d内两组患者总出血事件、大出血、出血性卒中、血小板减少发生率比较，差异均无统计学意义（P>0.05）。两组累积总出血事件发生率比较，差异无统计学意义（χ2=0.899，P=0.344）。两组患者住院期间MACE、死亡、再梗死、急性靶血管再次血运重建发生率比较，差异无统计学意义（ P>0.05）；高剂量组出院90 d内MACE、死亡发生率低于标准剂量组（ P<0.05）；高剂量组出院90 d内再梗死、急性靶血管再次血运重建发生率比较，差异无统计学意义（ P >0.05）。高剂量组累积 MACE 发生率低于标准剂量组（χ2=4.808，P=0.028）。Cox比例风险回归分析结果显示，高剂量替罗非班、肌酸激酶（ CK）是发生 MACE 的影响因素（ P <0.05）。结论在急性STEMI患者PPCI术中应用高剂量替罗非班较标准剂量替罗非班术后90 d内MACE发生率低，且并未增加出血风险。%Objective To investigate the efficacy and safety of high - dose tirofiban in primary percutaneous coronary intervention(PPCI)on patients with acute ST-elevation myocardial infarction(STEMI). Methods 134 acute STEMI patients who underwent PPCI in Beijing Tiantan Hospital from January 2010 to February 2011 were enrolled in the study. Using random number table method,subjects were divided into standard -dosage group( intravenous injection of 10μg/kg tirofiban within 3 mins followed by continuous intravenous infusion of 0. 150 μg·kg-1 ·min-1 ,SD group)and HD group( intravenous injection of 20μg/kg tirofiban followed by continuous intravenous infusion of 0. 225 μg · kg-1 · min-1 , HD group ), with 67 subjects in each group. The evaluation indicators included thrombolysis in myocardial infarction( TIMI)grade,echocardiography result,and ST-segment recovery rate( STR)at 90 minutes after operation. Safety endpoints during hospitalization and within 90 days after discharge included massive haemorrhage, hemorrhagic stroke and thrombocytopenia;effective endpoints, namely major adverse cardiac events(MACE),included death,re-infarction and acute target lesion revascularization. Results The two groups were not significantly different in basic data(P>0. 05). The two groups were not significantly different in the number of lesion coronary artery, IRA, stent diameter, stent length, the number of stent, unsuccessful PPCI, preoperative TIMI bleeding grading,unfractionated heparin(UFH),low molecular heparin,ACEI/ARB,β receptor inhibitor and statins(P>0. 05);HD group was higher than SD group in the rate of TIMI grade 3(χ2 =7. 309,P=0. 007). The two groups were not significantly different in IVST,LVPWT,LVEDD and LVESD on 90 days after operation(P>0. 05),and HD group was higher than SD group in LVEF on 90 days after operation(P<0. 05). The LVPWT,LVEDD,LVESD and LVEF of Stand-dose group and HD group on 90 days after operation were higher(P<0. 05)than those on the day of admission. HD group was higher than SD group in STR at 90 minutes after operation(t= -3. 678,P<0. 05). HD group was higher than SD group in ST-segment complete recovery rateand was lower than SD groupin ST - segment partial recovery rate(χ2 =9. 046,6. 351;P =0. 003, 0. 012);the two groups were not significantly different in the rate of noST - segment recovery(χ2 =1. 729,P =0. 189). During hospital stay and within 90 days after discharge,the two groups were not significantly different in the total number of bleeding events and the incidence rates of massive hemorrhea,hemorrhagic stroke and thrombocytopenia(P>0. 05). The two groups were not significantly different in the incidence rate of total bleeding events(χ2 =0. 899,P=0. 344). The two groups were not significantly different in the incidence rates of MACE,death,re-infarction and acute target lesion revascularization (P>0. 05);HD group was lower(P<0. 05)than SD group in the incidence rates of MACE and death within 90 days after discharge;HD group was not significantly different in the incidence rates of re - infarction and acute target lesion revascularization within 90 days after discharge( P >0. 05 ) . HD group was lower than SD group in the incidence rate of accumulated MACE(χ2 =4. 808,P=0. 028). The Cox multivariate regression analysis showed that HD tirofiban and CK are influencing factors for MACE(P<0. 05). Conclusion The application of HD tirofiban in PPCI on acute STEMI patients causes lower MACE incidence within 90 days after operation than SD tirofiban,and it causes no increase in the risk of bleeding events.