Effects of bivalirudin on acute myocardial infarction in patients undergoing emergency percutaneous coronary intervention

Background It.s an effective treatment to implement percutaneous coronary intervention in acute myocardial infarction patients,which rapidly achieve coronary reperfusion. However,many patients with no-reflow,leading to cardiovascular events,even sudden death. Bivalirudin has been used in anticoagulant therapy in PCI,which was characterized by rapid onset,strong anticoagulant effect and good safety. The HORIZONS-AMI study showed that bivalirudin reduced the risk of bleeding and death after PCI compared with heparin and glycoprotein IIb/IIIa antagonists. However,bivalirudin increased the risk of acute stent rethrombosis compared to unfractionated heparin and glycoprotein Ⅱb/Ⅲa antagonists. Therefore,the use of bivalirudin in emergency PCI was worth exploring. EUROMAX trial prompted that the patients who underwent emergency PCI and received intravenous use of bivalirudin during transit,might reduce the risk of bleeding. But there were few studies about bivalirudin on the effects of coronary reperfusion. This study was designed to investigate the effects of bivalirudin on coronary blood flow in patients with AMI and the safety of the drug. Methods All 120 AMI patients were divided into treatment group(n=60)and control group(n=60)according to random number method 1:1. In the treatment group,after coronary angiography and before PCI,the intravenous injection of bivalirudin(0.75mg/kg)was proportional,and then the intravenous maintenance was continued(1.75 mg·kg-1·h-1)for 5 h. In the control group,after coronary angiography and before PCI,intravenous injection of tirofiban(10 μg/kg)and unfractionated heparin(100 U/kg),followed by continuous intravenous injection of tirofiban(0.75 μg·kg-1·min-1)for 24 h. The TIMI blood flow classification,corrected TIMI frame number,TIMI myocardial perfusion grade(TMPG),Cardiac ultrasound parameters,serum NT-ProBNP and hs-CRP were recorded in the two groups before and after PCI. Major cardiovascular events(MACE),bleeding event,etc. were recorded. Results The ratio of coronary blood flow TIMI3 and TMPG3 after coronary intervention were significantly higher in treatment group than in control group(P0.05);TIMI frame number showed that the coronary blood flow of treatment group was significantly faster than the control group(P0.05). The LVEF value of the treatment group was higher than the control group after 30 d(P0.05). Postoperative serum NT-ProBNP and hs-CRP in the treatment group were significantly lower than those in the control group(P0.05). Conclusion Compared to tirofiban with heparin,using bivalirudin during acute PCI in AMI patients significantly improved coronary blood flow,reduced inflammatory response,reduced the incidence of MACE and bleeding,and improved the short-term prognosis.     

A randomized trial of deferred stenting versus immediate stenting to prevent no-or slow reflow in acute ST-elevation myocardial infarction(DEFER-STEMI)

Objectives To assess whether deferred stenting might reduce no-reflow and salvage myocardium in primary percutaneous coronary intervention(PCI) for ST-elevation myocardial infarction(STEMI). Background Noreflow is associated with adverse outcomes in STEMI. Methods A prospective single center randomized controlled proof-of-concept trial in reperfused STEMI patients with ≥ 1 risk factors for no-reflow. Randomization was to deferred stenting with an intention-to-stent 4-16 hours later or conventional treatment with immediate stenting. The primary outcome was the incidence of no / slow-reflow(TIMI ≤ 2). Cardiac magnetic resonance imaging(MRI) was performed 2 days and 6 months post-MI. Myocardial salvage was the final infarct size indexed to the initial area-at-risk. Results Of 411 STEMI patients(11 March 2012-21 November 2012), 101patients(mean age 60 years, 69% male) were randomized(n = 52 deferred group, n = 49 immediate stenting). The median(IQR) time to the second procedure in the deferred group was 9(6, 12) hours. Fewer patients in the deferred stenting group had no / slow-reflow [14(29%) vs. 3(6%); P = 0.006], no-reflow[7(14%) vs. 1(2%); P = 0.052] and intra-procedural thrombotic events [16(33%) vs. 5(10%); P =0.010]. TIMI coronary flow grades at the end of PCI were higher in the deferred stenting group(P = 0.018).Recurrent STEMI occurred in 2 patients in the deferred group before the second procedure. Myocardial salvage index at 6 months was greater in the deferred group [68(54, 82%) vs. 56(31, 72%); P = 0.031].Conclusion In high risk STEMI patients, deferred stenting in primary PCI reduced no-reflow and increased myocardial salvage.     

Prevention of No-flow With Distal Protection Device in Patients Underwent Percutaneous Coronary Intervention

Objectives To evaluate the feasibility and safety of distal protection device (PercuSurge) during percutaneous coronary intervention (PCI) in patients with acute coronary syndrome. Methods From October 2004 to August 2007, 40 patients with high risk acute coronary syndrome who received primary coronary intervention were included in this study. Patients were divided into two groups according to whether PercuSurge was attempted during PCI. The basic clinical characteristics, angiographic results, and follow-up data before discharge were compared. Coronary arteries blood flow thrombolysis in myocardial infarction (TIMI) grade, TIMI myocardial perfusion (TMP) grade and the rate of no-reflow were performed in all cases after PCI. Results There was no significant difference between the two groups in basic clinical characteristics and angiography before PCI (P>0.05). All patients underwent PCI successfully in both groups. In the PercuSurge group, PCI with PercuSurge guardwire protection was performed successfully in 18 patients. There was significant difference between the two groups in TIMI 3 flows gained in target vessels after PCI. Better percentage of TMP grade 3 of target vessels was achieved in PercuSurge group. Less no-reflow were found in PercuSurge group. There were lower peak troponin I and serum MB isoenzyme of creatine kinase levels, higher left ventricular ejection fraction and smaller left ventricular end-diastolic dimension in the PercuSurge group after PCI at the date before discharge (P<0.05). There was no major adverse cardiac events in PercuSurge group, only one patient died in the control group. Conclusions This study demonstrates that using the PercuSurge Guardwire system during PCI in high risk acute coronary syndrome patients to prevent no-reflow is feasibility and safety.     

急性ST段抬高心肌梗死急诊介入治疗后心肌再灌注不良对近、远期预后的影响

Objective To explore the prognostic impact of post primary percutaneous coronary intervention (PCI) reperfusion status on outcome in patients with acute ST-elevation myocardial infarction (STEMI). Methods A retrospective analysis was performed in 964 patients undergoing primary PCI for STEMI. Electrocardiogram and TIMI myocardial perfusion grade (TMPG) were analyzed by reader blinded to the clinical course. Patients were divided to four groups according to ST segment resolution (STR) and TMPG: group A were patients with good STR and TMPG(425/964), group B were patients with poor STR and good TMPG (239/964), group C were patients with good STR and poor TMPG (113/964) and group D were patients with poor STR and TMPG (113/964). Results Although TIMI grade Ⅲ flow was achieved after mechanical reperfusion, abnormal reperfusion was still present in about 1/3 patients as shown by poor STR or TMPG. Older age, cardiac dysfunction and diabetes, prolonged time of pain to balloon/emergency room are independent risk factors for abnormal reperfusion post PCI. Major aclverse cardiac events events in hospital ( RR = 64. 63, P < 0. 01 ) and during follow up( RR = 11.69, P < 0. 01 ) were significantly higher in group D than in group A. Conclusion Poor post PCI reperfusion status is associated with higher in hospital and during follow up major aclverse cardiac events event in STEMI patients.     

急性ST段抬高心肌梗死急诊介入治疗后心肌再灌注不良对近、远期预后的影响

Objective To explore the prognostic impact of post primary percutaneous coronary intervention (PCI) reperfusion status on outcome in patients with acute ST-elevation myocardial infarction (STEMI). Methods A retrospective analysis was performed in 964 patients undergoing primary PCI for STEMI. Electrocardiogram and TIMI myocardial perfusion grade (TMPG) were analyzed by reader blinded to the clinical course. Patients were divided to four groups according to ST segment resolution (STR) and TMPG: group A were patients with good STR and TMPG(425/964), group B were patients with poor STR and good TMPG (239/964), group C were patients with good STR and poor TMPG (113/964) and group D were patients with poor STR and TMPG (113/964). Results Although TIMI grade Ⅲ flow was achieved after mechanical reperfusion, abnormal reperfusion was still present in about 1/3 patients as shown by poor STR or TMPG. Older age, cardiac dysfunction and diabetes, prolonged time of pain to balloon/emergency room are independent risk factors for abnormal reperfusion post PCI. Major aclverse cardiac events events in hospital ( RR = 64. 63, P < 0. 01 ) and during follow up( RR = 11.69, P < 0. 01 ) were significantly higher in group D than in group A. Conclusion Poor post PCI reperfusion status is associated with higher in hospital and during follow up major aclverse cardiac events event in STEMI patients.     

A Comparative Study on Post-intervention Use of Tirofiban or Enoxaparin in Patients With Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention

Objectives To evaluate the efficacy and safety of post procedure use of platelet glycoprotein Ⅱb/Ⅲ a receptor in- hibitor （PGI） or low molecular weight heparin （LMWH） in patients with acute coronary syndrome （ACS） undergoing dual anti-platelet loading therapy and percutaneous coronary intervention （PCI）. Methods This was a prospective randomized grouping controlled study in 174 patients with ACS received aspirin 300 mg plus clopidogrel 600mg loading before PCI. After procedure, patients were randomized to intravenous tirofiban for 12 -24 hours （tirofiban group） or subcutaneous enoxaparin for 5 days （enoxaparin group）. Cardiac ischemic events, major bleeding complications, minor bleeding complications, thrombocytopenia, and vascular access complications in both groups were investigated. Results Cardiac ischemic events, major bleeding complications, minor bleeding complications, thrombocytopenia, and vascular access complications in tirofiban group were 8.0% , 3.4% , 6.8% , 3.4% , and 3.4% , respectively. In enoxaparin group, aforementioned event rates were 7%, 2. 3%, 6. 0%, 2. 3%, and 5.8%, respectively. No statistical significance was found between two groups. Conclusions In the setting of dual anti-platelet medication loading and PCI for the treatment of ACS, it is effective to use tirofiban or enoxaparin for aggressive post procedure antithrombotic therapy. It comes with a very low major bleeding complication rate. Use of GPI for 12 to 24 hours was comparable to use of LMWH for 5 days in efficacy and safety.     

老年急性冠状动脉综合征患者替罗非班冠状动脉和静脉用药的疗效比较

目的 分析老年急性冠状动脉(冠脉)综合征(ACS)患者替罗非班不同负荷和不同用药途径对心肌灌注和30 d主要不良心血管事件(MACE)的影响,探讨替罗非班的负荷用药最佳途径.方法 2009年7月至2010年7月,连续入选120例老年ACS患者,均行经皮冠状动脉介入术(PCI),术前开始用替罗非班.根据负荷给药途径不同分为两组:冠脉内用药组和静脉用药组,各60例.观察两组患者PCI后冠脉血流、心肌灌注及PCI术后30 d的MACE.结果 冠脉内用药组病变冠脉的急性心肌梗死溶栓试验(TIMI)血流分级3级、TIMI心肌灌注分级(TMPG)3级率明显高于静脉用药组[分别为53例(88.3%)、38例(63.3%)和40例(66.7%)],两两比较,均P＜0.05,但两组患者院内和PCI后30 d的MACE[分别为1(1.7%)和0,3(5.0%)和5(8.3%)]及不同程度出血和血小板减少症发生率比较差异均无统计学意义.结论 老年ACS患者PCI前冠脉内使用负荷剂量替罗非班与静脉内用药途径比较,能更有效地增加冠状动脉血流及心肌水平的灌注.

Abstract：

Objective To analyze the therapeutic effect of intracoronary versus intravenous bolus tirofiban on myocardial perfusion and major cardiovascular events (MACE) in elderly patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS) and explore the optimal route of tirofiban application. Methods From July 2009 to July 2010, 120 NSTE-ACS patients undergoing percutaneous coronary intervention (PCI ) were consecutively enrolled in this study. They were randomly divided into two groups: intracoronary (60 cases) versus intravenous (60 cases) bolus tirofiban. Thrombolysis in myocardial infarction (TIMI) flow, TIMI myocardial perfusion grade (TMPG) and MACE 30 days after PCI were observed. Results The incidence of TIMI flow and TMPG 3 grade in intracoronary group were higher than in intravenous group [53(88.3%) vs. 38(63.3%); 53(88.3%) vs. 40(66.7%), respectively, both P＜0.05]. However, MACE incidence and bleeding complications during hospital 30 days after PCI had no significant difference between the two groups [1 (1.7%) vs. 0; 3(5.0%) vs. 5(8.3%)], which were not statistically significant (P＞0.05). Conclusions Intracoronary bolus tirofiban before PCI more effectively increases coronary blood flow and myocardium blush than intravenous route in elderly NSTE-ACS patients.     

Comparison Between Upstream Tirofiban and Downstream Tirofiban in Patients With Non-ST-segment Elevation Acute Coronary Syndromes at High-risk Undergoing Percutaneous Coronary Interventions： Efficacy and Safety

Objectives To compare the efficacy and safety of upstream tirofiban with downstream tirofiban in patients with non- ST-segment elevation acute coronary syndromes （NSTE-ACS） at high-risk undergoing percutaneous coronary intervention （PCI）. Methods Two hundred and four patients with NSTE-ACS at high-risk undergoing PCI were randomized to upstream （4 -6 hours before coronary angiography） tirofiban or downstream （with the guidewire crossing the lesion） tirofiban. We evaluated myocardial damage after PCI by qualitatively analyzing cardiac troponin I （cTnI） and MB isoenzyme of creatine kinase （CK-MB）. Platelet aggregation inhibition and thrombolysis in myocardial infarction （TIMI） flow grade were assessed. The incidences of major adverse cardiac events （MACE） at 24-hour, 90-day and 180-day after PCI were followed up. The incidences of bleeding complications and thrombocytopenia during tirofiban administration were recorded. Results There were 102 patients with NSTE-ACS randomly assigned to upstream group and downstream group respectively. The peak serum levels of cTnI within 48 hours after PCI were significantly lower with upstream tirofiban than downstream tirofiban （0.34 vs 0. 61 ; P 〈 0.05 ）. Post-procedural cTnI elevation within 48 hours was significantly less frequent among patients who received upstream tirofiban than downstream tirofiban （63 % vs 82%, P 〈 0. 05 ）. The peak serum levels of CK-MB as well as post-procedural CK-MB elevation within 48 hours after PCI were not significantly different between the two groups （ 15 vs 18 and 38% vs 43% ; respectively; P 〉 0. 05 ）. ECG changes and the inhibition of platelet aggregation between two groups were similar （ P 〉 0.05 ）. Although the inci- dences of MACE at 90-day and 180-day after PCI were not statistically different, they were consistently lower with upstream tirofiban （3 % vs 6% and 6% vs 16% ; P 〉 0.05 ）. The incidences of bleeding complications and thrombocyto- penia were similar in the two groups （ 11% vs 9% ; P 〉 0.05 ）. Conclusions Among patients with NSTE-ACS at high-risk undergoing PCI, upstream tirofiban is associated with attenuated myocardial damage without increasing complications. （ S Chin J Cardiol 2009; 10（4） ： 179 -185）     

Nursing observation of transradial coronary intervention combined with tirofiban hydrochloride for acute coronary syndrome in elderly patients

Background As the most effective approach in treatment of revascularization in coronary perfusion for acute coronary syndromes(ACSs), percutaneous coronary intervention(PCI) can also increase the risk of detachment of thrombus and embolism of distal microcirculation. Tirofiban hydrochloride is a reversible antagonist of platelet glycoprotein Ⅱb / Ⅲa receptor, which can inhibit platelet aggregation quickly. However,it may also increase the risk of bleeding when in combination with other anti-thrombus drugs. It is important in medication observation for charge nurse when using Ⅱ b / Ⅲ a receptor inhibitor. Methods For 116 elderly patients with ACS who had transradial coronary interventional therapy combined with tirofiban hydrochloride,we conducted medication care, nursing observation of hemorrhage, nursing of puncture of upper limb,postoperative adverse cardiovascular events, observation of myocardial perfusion, blood flow and health education. Results A total of 10 patients had mild bleeding, no serious bleeding, and 2 with major adverse cardiac event(MACE). Conclusions Tirofiban hydrochloride after PCI can significantly reduce cardiovascular events in acute coronary syndromes, but there is an increased risk of bleeding. It showed that strengthen inspection, closely observe condition and detecting bleeding in time after PCI can significantly reduce postoperative complications for charge nurses.     

冠状动脉介入术联合冠状动脉腔内注入替罗非班治疗急性ST段抬高性心肌梗死的临床观察

目的 探讨冠状动脉介入术联合冠状动脉腔内注入替罗非班治疗ST段抬高性急性心肌梗死(STEAMI)的有效性与安全性及对冠状动脉内血栓的影响.方法 2007年2月至2010年8月诊断明确并经冠状动脉造影证实梗死相关血管(IRA)为急性闭塞病变,且成功进行急诊冠状动脉介入治疗术(PCI)的128例STEAMI患者,随机分为试验组和对照组.试验组于冠状动脉造影后立即通过造影导管于IRA按10 μg/kg替罗非班在5 min内完成腔内注入,对照组于冠状动脉造影后立即通过造影导管于注入等容积量生理盐水.观察两组患者IRA注入替罗非班或生理盐水10 min后的冠状动脉内血栓及血管再通状况,术后院内出血并发症情况,随访两组患者术后1个月内心脏不良事件及心功能.结果 试验组IRA注入替罗非班10 min后33例血栓负荷减低,其中26例心肌梗死试验性溶栓治疗(TIMI)血流分级≥1级,对照组6例血栓负荷减低,3例TIMI≥1级,两组比较差异有统计学意义(P＜0.01).两组患者术后1个月内心脏不良事件(分别为2例和3例)比较,差异无统计学意义(P＞0.05).试验组术后1个月时的美国纽约心脏病学会(NYHA)心功能分级及左心室射血分数均优于对照组(P＜0.05).结论 冠状动脉腔内注入替罗非班联合冠状动脉介入术有助于ST段抬高性急性心肌梗死IRA的血栓消退及血管再通,有效且安全.

Abstract：

Objective To assess the clinical efficacy and safety of the combination of intracoronary tirofiban infusion(ICTI) plus percutaneous coronary intervention(PCI) in patients with acute ST-elevation myocardial infarction (STEAMI). Methods The 128 cases with STEAMI were enrolled in this study. They were randomly divided into trial group and control group. The 10 μg/kg tirofiban were infused into the infarct related artery (IRA) within 5 minutes through the cather after coronary angiography in trial group (n=64). Normal saline in matched dose was infused into IRA after coronary angiography in control group (n=64). The coronary thrombosis and revascularization status were assessed within 10 minutes after injection. Postoperative bleeding complications were observed in all cases. Adverse cardiovascular events and cardiac function were followed up within 1 month in all cases. Results There were 33 cases whose thrombus burden was reduced within 10 minutes after the infusion of tirofiban in trial group, including 26 cases of thrombolysis in myocardial infarction (TIMI) ≥1. There were 6 cases whose thrombus burden was reduced within 10 minutes after the infusion of normal saline in control group, including 3 cases TIMI ≥ 1. The coronary thrombosis and revascularization status were better in trial group rather than in control group (P＜0.01). Adverse cardiovascular events occurred in 5 cases within 1 month, including 2 cases in trial group and 3 cases in control group (P＞0.05). New York heart association functional class and ejection fraction values were better in trial group rather than in control group within 1 month (P＜0.05). Postoperative bleeding complications occurred in 14 cases by TIMI criteria , including severe and mild bleeding in 2 cases in trial group and 1 cases in control group (P＞0.05), but no significant bleeding occurred in 8 cases in trial group and in 3 cases in control group (P＜0.01). Conclusions The combination of intracoronary infusion of tirofiban plus PCI is effective and safe for thrombolysis and revascularization in IRA in patients with STEAMI.