Bivalirudin compared with IIb/IIIa inhibitors in patients with in-stent restenosis undergoing intracoronary brachytherapy

BACKGROUND: Bivalirudin is replacing heparin in percutaneous coronary interventions (PCIs), including vascular brachytherapy (VBT). The aim of the study was to compare bivalirudin with eptifibatide in patients with in-stent restenosis (ISR) undergoing PCI and VBT. METHODS: One hundred forty-four patients treated with bivalirudin as a single antithrombotic agent were compared with 150 patients treated with eptifibatide. Bivalirudin as a bolus of 0.75 mg/kg followed by 1.75 mg/kg/h infusion until the end of the procedure, and eptifibatide as a double bolus of 180 microg/kg followed by 2 microg/kg/min infusion for 18 h after the procedure were used. The main outcome measures were in-hospital events and 30-day clinical outcomes. RESULTS: Baseline clinical characteristics were similar except that patients in the eptifibatide group were younger (P=.02) and had more saphenous vein graft lesions (P<.001). Patients in the bivalirudin group had a higher number of lesions in the right coronary artery (P<.001) and a higher number of vessels treated (P<.001). Postprocedure creatinine phosphokinase (CPK)-MB levels were significantly lower in the bivalirudin group (P<.03). In-hospital events showed significantly less minor bleeding (P=.01) and a trend toward lower major bleeding and major adverse cardiac events (MACE) in the bivalirudin group (P=.06). Thirty-day outcomes showed a significantly lower incidence of non-Q-wave myocardial infarction (MI) in the bivalirudin group (P=.004). CONCLUSION: Bivalirudin, as a single antithrombotic agent during PCI and VBT, is associated with significantly lower postprocedural CPK-MB elevation, minor bleeding complications, 30-day non-Q-wave MI rates, and a trend toward lower major bleeding and in-hospital MACE when compared with eptifibatide.     

比伐芦定在高出血风险患者介入治疗中抗凝疗效和安全性评价

目的：评价比伐芦定在高出血风险急性冠脉综合征（ACS）患者介入治疗中抗凝疗效和安全性。 方法：随机将入选的ACS患者分为比伐芦定组（104例）和肝素组（102例）,PCI术中分别采用比伐芦定和普通肝素进行抗凝治疗,并根据术中冠脉病变情况决定是否联用血小板糖蛋白IIb/IIIa拮抗剂(glycoprotein IIb/IIIa inhibitor, GPI)。比较两组间一般情况及PCI相关资料,并对两组30天内的出血、支架血栓事件及主要不良心血管事件（MACE）进行统计分析。 结果：两组间支架血栓事件及MACE发生率无显著性差异（P>0,05）, 比伐芦定组出血发生率显著降低（P<0.05）,其中以轻度出血发生率减少更为显著,严重出血方面两组间无统计学性差异（1.9% vs2.9%,P>0.05）,但比伐芦定组有较低的严重出血风险趋势。 结论：比伐芦定在高出血风险的ACS患者的PCI治疗中抗凝治疗是安全有效的,并降低出血风险。     

Bivalirudin Inhibits Periprocedural Platelet Function and Tissue Factor Expression of Human Smooth Muscle Cells

Aim: A major concern of stent implantation after percutaneous coronary intervention (PCI) is acute stent thrombosis. Effective inhibition of periprocedural platelet function in patients with coronary artery disease (CAD) leads to an improved outcome. In this study, we examined the periprocedural platelet reactivity after administrating bivalirudin during PCI compared to unfractionated heparin (UFH) administration. Further, the effect of bivalirudin on induced tissue factor (TF) expression in smooth muscle cells (SMC) was determined. Methods: Patients with CAD (n = 58) and double antithrombotic medication were treated intraprocedural with UFH (n = 30) or bivalirudin (n = 28). Platelet activation markers were flow cytometrically measured before and after stenting. The expression of TF in SMC was determined by real‐time PCR and Western blotting. The thrombogenicity of platelet‐derived microparticles and SMC was assessed via a TF activity assay. Results: Bivalirudin significantly diminished the agonist‐induced platelet reactivity post‐PCI. Compared to UFH treatment, the adenosine diphosphate (ADP) and thrombin receptor‐activating peptide (TRAP)‐induced thrombospondin expression post‐PCI was reduced when bivalirudin was administrated during intervention. In contrast to UFH, bivalirudin reduced the P‐selectin expression of unstimulated and ADP‐induced platelets post‐PCI. Moreover, bivalirudin inhibited the thrombin‐, but not FVIIa‐ or FVIIa/FX‐induced TF expression and pro‐coagulant TF activity of SMC. Moreover, bivalirudin reduced the TF activity of platelet‐derived microparticles postinduction with TRAP or ADP. Conclusions: Bivalirudin is better than UFH in reducing periprocedural platelet activation. Moreover, thrombin‐induced TF expression is inhibited by bivalirudin. Thus, bivalirudin seems to be a better anticoagulant during PCI than UFH.     

Bivalirudin in PCI: an overview of the REPLACE-2 trial

The Randomized Evaluation in PCI Linking Angiomax to Reduced Clinical Events (REPLACE)-2 trial is one of the largest acute randomized controlled trials evaluating the efficacy of two anticoagulant strategies during contemporary urgent or elective percutaneous coronary intervention (PCI). The direct thrombin inhibitor, bivalirudin, with provisional use of glycoprotein IIb/IIIa (GP IIb/IIIa) inhibitor was compared to low-dose unfractionated heparin (UFH) plus planned GP IIb/IIIa inhibitor. At 30-day follow-up, the primary quadruple composite endpoint (death, myocardial infarction (MI), urgent repeat revascularization, or in-hospital major bleeding) occurred in 9.2% of patients in the bivalirudin group versus 10.0% of patients in the UFH plus GP IIb/IIIa inhibitor group. The secondary triple composite endpoint (death, MI, urgent repeat revascularization) occurred in 7.6% of patients in the bivalirudin group compared with 7.1% of patients in the UFH plus GP IIb/IIIa inhibitor group. Both endpoints met formal statistical criteria for noninferiority to UFH plus GP IIb/IIIa inhibitor. By imputed comparison from historic GP IIb/IIIa trials between bivalirudin versus UFH alone, REPLACE-2 demonstrated that bivalirudin was superior to UFH alone with respect to the quadruple and triple composite endpoints. Furthermore, bivalirudin plus provisional GP IIb/IIIa blockade was associated with a significant reduction in in-hospital bleeding (2.4% vs. 4.1%; p < 0.001). At 6 months' follow-up, there was no significant difference in rates of death, MI, or revascularization between the two groups. Furthermore, there was no evidence that the early, nonsignificant 0.5% excess non-Q-wave MI in the bivalirudin group translated into later mortality. There was a trend toward decreased mortality at 6 months in the bivalirudin arm (0.95% vs. 1.35%; p = 0.148). The relative efficacy of bivalirudin versus UFH plus GP IIb/IIIa inhibitor was similar in several high-risk subgroups, including patients with diabetes mellitus or prior MI, women, the elderly (age > 65 years), and patients undergoing PCI of bypass grafts. Bivalirudin represents an exciting alternative to UFH plus GP IIb/IIIa inhibitor in patients undergoing urgent and elective PCI with similar suppression of ischemic events, fewer bleeding complications, and the potential for greater cost savings and ease of administration.     

比伐芦定在急性冠脉综合征患者PCI围术期的有效性及安全性

目的 探索比伐芦定在急性冠脉综合征（ACS）患者接受经皮冠状动脉介入（PCI）治疗围术期应用的有效性及安全性。方法 收集2018年1月～2020年6月收治的接受PCI治疗且术前应用阿司匹林与替格瑞洛作为双联抗血小板治疗的ACS患者309例,根据围术期应用的抗凝方案分为比伐芦定组和肝素联用血小板糖蛋白Ⅱb/Ⅲa受体抑制剂（GPI）组（肝素GPI组）,分别收集到58例和251例。进行1:1比例的倾向性评分匹配（两组均n=50）,通过门诊及电话随访统计终点事件发生情况。主要终点为术后30 d净不良临床事件（NACE）发生率,定义为包括符合美国出血学术研究联合会出血标准（BARC）的全部出血和主要不良心脑血管事件（MACCE）,即包括各种原因引起死亡、紧急的靶罪犯血管需行再次血运重建（uTVR）、心肌梗死、卒中的复合终点。次要终点为术后30 d和6月内的MACCE事件及全部出血,以及术后6月内的NACE。结果 两组术后30 d的NACE事件、MACCE事件、全部出血事件以及术后6月发生的NACE事件、MACCE事件及全部出血的发生率差异均无统计学意义。两组术后30 d发生符合BARC(3～5)...     

Bleeding risk and outcomes of Bivalirudin versus Glycoprotein IIb/IIIa inhibitors with targeted low-dose unfractionated Heparin in patients having percutaneous coronary intervention for either stable or unstable angina pectoris

For patients undergoing elective percutaneous coronary intervention (PCI), procedural anticoagulation with bivalirudin was previously shown to significantly reduce bleeding complications at the cost of a modest increase in ischemic events compared with unfractionated heparin (UFH) and glycoprotein IIb/IIIa inhibitors (GPIs). However, the excess bleeding in patients treated with UFH and GPIs may have been caused by excessively high UFH doses and increased activated clotting times. This study sought to determine the bleeding risk of targeted low-dose UFH with GPIs compared with bivalirudin in patients undergoing elective PCI. Of 1,205 patients undergoing elective PCI, 602 underwent PCI with adjunctive UFH and GPIs with the UFH dose targeted to an activated clotting time of approximately 250 seconds, and 603 patients matched for baseline characteristics underwent PCI with bivalirudin. Outcomes were analyzed for major bleeding (hematocrit decrease >15%, gastrointestinal bleed, or major hematoma) and 6-month major adverse cardiac events (death, myocardial infarction, and target-lesion revascularization). The maximum activated clotting time achieved was 261.7 +/- 61.6 seconds in the UFH/GPI group and 355.4 +/- 66.6 in the bivalirudin group (p <0.001). In-hospital major bleeding rates were similar between groups (1.8% UFH/GPI vs 1.7% bivalirudin; p = 0.83), as were transfusion requirements (1.2% UFH/GPI vs 0.5% bivalirudin; p = 0.61). The 6-month major adverse cardiac event rate was also similar between groups (9.5% UFH/GPI vs 9.0% bivalirudin; p = 0.81). In conclusion, there were no significant differences in major bleeding and 6-month major adverse cardiac events for patients undergoing elective PCI treated with targeted low-dose UFH and GPIs compared with those treated with bivalirudin.     

Meta-analysis comparing bivalirudin versus heparin monotherapy on ischemic and bleeding outcomes after percutaneous coronary intervention

With femoral access, bivalirudin decreases risks of major bleeding after percutaneous coronary intervention (PCI) and provides better net clinical benefit compared to unfractionated heparin (UFH) plus planned glycoprotein IIb/IIIa inhibitors. Whether this benefit exists compared to UFH monotherapy is less clear. We performed a systematic review and meta-analysis to compare outcomes in patients undergoing transfemoral PCI with UFH or bivalirudin. Randomized trials (n = 3) and observational studies (n = 13) comparing bivalirudin to UFH monotherapy were reviewed. Primary outcomes were 30-day rates of major adverse cardiovascular events (MACEs) including death, myocardial infarction (MI), urgent revascularization, as well as all-cause mortality, MI, major bleeding, and blood transfusion. We collected data from 16 studies involving 32,492 patients undergoing PCI. Most observational studies were performed in the United States, whereas all randomized trials were done in Europe. Compared to UFH monotherapy, bivalirudin was associated with similar risk of MACEs (odds ratios [OR] 0.92, 95% confidence interval [CI] 0.75 to 1.12), a substantial 45% relative decrease in major bleeding (OR 0.55, 95% CI 0.43 to 0.72), and a trend in the decrease of transfusion (OR 0.87, 95% CI 0.70 to 1.08). A decrease in mortality was seen in observational studies (OR 0.62, 95% CI 0.45 to 0.85) but remained inconclusive in randomized trials (OR 0.63, 95% CI 0.20 to 2.01). MI rate was similar with the 2 anticoagulants. In conclusion, in patients undergoing transfemoral PCI, the benefit of bivalirudin over UFH monotherapy is driven by a significant decrease in major bleeding with similar rates of MACE. As PCI practice moves toward other bleeding-avoidance strategies such as the radial approach, future studies should focus on the interaction between anticoagulant strategy and access-site choice.     

国产比伐卢定用于冠状动脉介入治疗术中抗凝的疗效和安全性评价

目的:评估国产比伐卢定应用于择期冠状动脉介入治疗术(PCI)中抗凝治疗的疗效及安全性.方法:采用随机、单盲、多中心临床试验设计,随机将接受择期PCI的患者分为比伐卢定组和肝素组,在PCI术中分别采用比伐卢定或普通肝素抗凝治疗,主要疗效评价指标为术中测定激活的全血凝固时间(ACT)、手术成功率(靶病变术后狭窄程度小于20%并24 h内无冠状动脉事件发生)及30天无心血管事件生存率,主要安全性评价指标为轻度及重度出血.结果:共有218例患者入选,实际入组完成试验207例,比伐卢定组(n=105)和肝素组(n=102).用药后5 min除肝素组2例需要追加剂量外,其余两组患者PCI术中均能维持ACT>225 s,两组差异无统计学意义(P>0.05);比伐卢定组和肝素组PCI手术成功率和30天无心脏事件生存率均分别为100%和98.04%(P>0.05),差异无统计学意义.比伐卢定组和肝素组24 h内轻度出血的发生率分别为0.95%和6.86%(P<0.05)、30天内轻度出血发生率分别为1.9%和8.8%(P<0.05),肝素组有1例发生严重消化道出血.结论:国产比伐卢定能安全有效地应用于择期PCI术中抗凝治疗,疗效不劣于肝素且出血副作用低于肝素.     

The impact of unfractionated heparin or bivalirudin on patients with stable coronary artery disease undergoing percutaneous coronary intervention

Objectives

To compare bleeding and clinical events of patients with stable angina or silent ischemia undergoing percutaneous coronary intervention (PCI) treated with unfractionated heparin (UFH) or bivalirudin.

Background

Few direct comparisons between UFH monotherapy versus bivalirudin exist for patients with stable ischemic heart disease undergoing PCI.

Methods

A prospective, investigator‐initiated, single‐center, single‐blinded, randomized trial of UFH versus bivalirudin was conducted. The primary endpoint was all bleeding (major and minor) from index‐hospitalization to 30 days post discharge. Secondary endpoints included major adverse cerebral and cardiovascular events (MACCE) and net adverse clinical events (NACE).

Results

Two‐hundred‐sixty patients were randomized for treatment with either UFH (n = 123) (47%) or bivalirudin (n = 137) (53%) There were no significant differences in baseline clinical and angiographic characteristics between the two groups. Primary endpoint was similar in both groups (10.9% with bivalirudin vs 7.3% with UFH [P = 0.31]). Major bleeding rates were 5.8% and 2.4%, respectively (P = 0.17). There was a higher MACCE (3.5% vs 0%, P = 0.03) and NACE (8.8% vs 2.4%, P = 0.03) rate with bivalirudin compared to UFH, respectively. Bivalirudin had increased odds of NACE (OR = 3.65, 95% CI: 1.00‐13.3.6). Death and stent thrombosis rates were low and similar in both groups. Radial access was associated with fewer bleeding events compared to femoral access but not statistically significant (P = 0.29).

Conclusions

Among patients with stable angina or silent ischemia, there was no difference between UFH and bivalirudin in bleeding rates up to 30‐days post‐PCI. MACCE and NACE were higher among the bivalirudin group. Radial access was associated with a numerically lower rate of bleeding compared with femoral access.     

Antithrombotic efficacy of bivalirudin compared to unfractionated heparin during percutaneous coronary intervention for acute coronary syndrome

Bivalirudin is associated with an increased risk of acute stent thrombosis (AST) compared to unfractionated heparin (UFH) in acute coronary syndrome patients (ACS) during short-duration percutaneous coronary intervention (PCI). The mechanisms involved are unknown. We aimed to investigate the antithrombotic efficacy of bivalirudin compared to UFH during PCI. In a monocenter study, we prospectively enrolled 30 patients undergoing PCI for a non–ST elevation ACS. They were randomly assigned to a single intravenous (IV) bolus of UFH (70 IU/kg) or an IV bolus of bivalirudin 0.75 mg/kg followed by a 1.75 mg/kg/h infusion during PCI. All patients received a loading dose (LD) of 180 mg of ticagrelor at the time of PCI. The VASP index and activated partial thromboplastin time (aPTT) were used to assess the course of platelet reactivity (PR) and antithrombotic activity. The two groups were similar regarding baseline, angiographic, and interventional characteristics. There was no difference between the two groups in the course of PR following ticagrelor LD. An optimal PR inhibition was obtained 4 h after the LD of ticagrelor. The level of antithrombotic activity was significantly lower in the bivalirudin group compared to the UFH group (p < 0.001) during PCI but similar at 2 and 4 h post-PCI. We observed that, in ACS undergoing PCI, the antithrombotic efficacy of an IV bolus of bivalirudin is significantly lower than that of a 70-IU/kg UFH bolus. This could contribute to the excess in thrombotic acute events observed during short-duration PCI.     

Comparison of safety and efficacy of bivalirudin versus unfractionated heparin in high-risk patients undergoing percutaneous coronary intervention (from the Anti-Thrombotic Strategy for Reduction of Myocardial Damage During Angioplasty-Bivalirudin vs Heparin study)

Bivalirudin, a direct thrombin inhibitor, is as effective as unfractionated heparin (UFH), with decreased bleeding in patients with acute coronary syndromes who undergo percutaneous coronary intervention (PCI). The aim of this study was to evaluate the effectiveness of bivalirudin versus UFH in selected PCI patients at high bleeding risk. Four hundred one consecutive patients who underwent PCI fulfilling ≥ 1 enrollment criterion (age >75 years, chronic renal failure, and diabetes mellitus) were randomized to bivalirudin (bolus 0.75 mg/kg followed by infusion during the procedure; n = 198) or UFH (75 IU/kg; n = 203). In the overall population, 39% were aged >75 years, 22% had renal failure, 63% had diabetes, and 29% had acute coronary syndromes. The primary efficacy end point was the 30-day incidence of major adverse cardiac events (cardiac death, myocardial infarction, stent thrombosis, or target vessel revascularization). The primary safety end point was the occurrence of any bleeding or entry-site complications after PCI. All patients were preloaded with clopidogrel 600 mg. Glycoprotein IIb/IIIa inhibitors were used at the operators' discretion. Thirty-day major adverse cardiac event rates were 11.1% in the bivalirudin group and 8.9% in the UFH group (p = 0.56); the primary efficacy end point was reached mainly because of periprocedural myocardial infarction; 1 patient in the bivalirudin group had stent thrombosis. Occurrence of the primary safety end point was 1.5% in the bivalirudin group and 9.9% in the UFH group (p = 0.0001); this benefit was essentially driven by the prevention of entry-site hematomas >10 cm (0.5% vs 6.9%, p = 0.002). In conclusion, Anti-Thrombotic Strategy for Reduction of Myocardial Damage During Angioplasty-Bivalirudin vs Heparin (ARMYDA-7 BIVALVE) indicates that bivalirudin, compared with UFH, causes significantly lower bleeding and has a similar incidence of major adverse cardiac events in patients with older age, diabetes mellitus, or chronic renal failure who undergo PCI.     

Novel Approaches for Preventing or Limiting Events (Naples) III Trial: Randomized Comparison of Bivalirudin Versus Unfractionated Heparin in Patients at Increased Risk of Bleeding Undergoing Transfemoral Elective Coronary Stenting

ObjectivesThis study sought to assess the safety and the efficacy of bivalirudin compared with unfractionated heparin (UFH) alone in the subset of patients at increased risk of bleeding undergoing transfemoral elective percutaneous coronary intervention (PCI).BackgroundBivalirudin, a synthetic direct thrombin inhibitor, determines a significant decrease of in-hospital bleeding following PCI.MethodsThis is a single-center, investigator-initiated, randomized, double-blind, controlled trial. Consecutive biomarker-negative patients at increased bleeding risk undergoing PCI through the femoral approach were randomized to UFH (UFH group; n = 419) or bivalirudin (bivalirudin group; n = 418). The primary endpoint was the rate of in-hospital major bleeding.ResultsThe primary endpoint occurred in 11 patients (2.6%) in the UFH group versus 14 patients (3.3%) in the bivalirudin group (odds ratio: 0.78; 95% confidence interval: 0.35 to 1.72; p = 0.54). Distribution of access-site and non–access-site bleeding was 18% and 82% in the UFH group versus 50% and 50% in the bivalirudin group (p = 0.10).ConclusionsThe results of this randomized study, carried out at a single institution, suggest that there is no difference in major bleeding rate between bivalirudin and UFH in increased-risk patients undergoing transfemoral PCI. (Novel Approaches in Preventing and Limiting Events III Trial: Bivalirudin in High-Risk Bleeding Patients [NAPLES III]; NCT01465503)     

比伐芦定在尿激酶溶栓治疗后冠状动脉介入过程中应用的安全性

目的:初步评价ST段抬高型急性心肌梗死（STEMI）尿激酶溶栓治疗后急诊经皮冠状动脉介入治疗（PCI）过程中应用比伐芦定的安全性。方法: 回顾分析2012年10月~2013年8月于尿激酶溶栓后3~24 h内行急诊PCI治疗过程中应用了比伐芦定16例患者的资料（比伐芦定组）,按1∶2匹配选取既往急诊PCI治疗过程中常规应用普通肝素的此类患者资料,按性别、年龄、病变血管相匹配纳入32例患者作为对照组（普通肝素组）,分析术后30 d内的主要终点事件（包括全因死亡、再发心肌梗死）以及严重出血性并发症的发生情况。结果: 两组基线资料对比,差异无显著意义。30 d内普通肝素组1例发生主要终点事件及1例严重出血并发症,两组间主要终点事件和严重出血并发症发生率差异无统计学意义。结论: STEMI尿激酶溶栓治疗后行急诊PCI过程中应用比伐芦定相对安全。     

Efficiency and safety of bivalirudin in patients undergoing emergency percutaneous coronary intervention via radial access: A subgroup analysis from the bivalirudin in acute myocardial infarction versus heparin and GPI plus heparin trial

Objectives: To explore the efficiency and safety of bivalirudin in patients undergoing emergency percutaneous coronary intervention via radial access. Background: Bivalirudin reduces bleeding risks over heparin in patients undergoing PCI. However, bleeding advantages of bivalirudin in patients undergoing transradial intervention is uncertain. Methods: In the BRIGHT trial, 1,723 patients underwent emergency PCI via radial access, with 576 patients in the bivalirudin arm, 576 in the heparin arm and 571 in the heparin plus tirofiban arm. The primary outcome was 30‐day net adverse clinical event (NACE), defined as a composite of major cardiac and cerebral events or any bleeding. Results: 30‐day NACE occurred in 5.7% with bivalirudin, 7.8% with heparin alone (vs. bivalirudin, P = 0.159), and 10.3% with heparin plus tifofiban (vs. bivalirudin, P = 0.004). The 30‐day bleeding rate was 0.9% for bivalirudin, 2.3% for heparin (vs. bivalirudin, P = 0.057), and 5.8% for heparin plus tirofiban (vs. bivalirudin, P < 0.001). Major cardiac and cerebral events (4.9 vs. 5.7 vs. 4.6%, P = 0.899), stent thrombosis (0.5 vs. 0.5 vs. 0.7%, P = 0.899) and acquired thrombocytopenia (0.2 vs. 0.5 vs. 0.9%, P = 0.257) at 30 days were similar among three arms. The interaction test for PCI access and randomized treatment showed no significance on all bleeding (P > 0.05). Conclusions: The bleeding benefit of bivalirudin was independent of artery access. Bivalirudin lead to statistical reduction on bleeding risks in comparison to heparin plus tirofiban, and only small numerical difference in comparison to heparin, with comparable risks of ischemic events and stent thrombosis in patients with acute myocardial infarction (AMI) undergoing emergency transradial PCI. © 2016 Wiley Periodicals, Inc.     

Angiographic and clinical outcomes of bivalirudin versus heparin in patients with acute coronary syndrome undergoing percutaneous coronary intervention

BACKGROUND: Heparin with adjunctive glycoprotein IIb/IIIa platelet receptor (GP IIb/IIIa) inhibitors has demonstrated its effectiveness in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). Bivalirudin, a direct thrombin inhibitor, has recently been shown to be an effective alternative for patients undergoing elective PCI. OBJECTIVES: To assess the angiographic and clinical outcomes of adjunctive pharmacological strategies in a high-risk population presenting with ACS. METHODS: Of 891 consecutive PCI patients with ACS, 304 received bivalirudin (60.5% male, 68+/-11 years) and were compared with 283 who received heparin (58.7% male, 66+/-12 years). A 30-day major adverse cardiac event was defined as the occurrence of cardiac death, nonfatal myocardial infarction, urgent revascularization or major hemorrhage. RESULTS: Adjunctive GP IIb/IIIa inhibitors were used in 14.1% of the bivalirudin group and in 72.4% of the heparin group (P<0.010). The occurrence of Thrombolysis In Myocardial Infarction (TIMI) flow less than grade 3 was lower and the achievement of angiographic success was higher in the bivalirudin group than in the heparin group (5.2% versus 8.2%, 94.7% versus 89.7%, P=0.039 and P<0.010, respectively). There was no difference between groups in the incidence of bleeding events (bivalirudin 2.0% versus heparin 3.5%, P not significant) and in 30-day major adverse cardiac events (bivalirudin 8.3% versus heparin 5.7%, P=0.223). CONCLUSIONS: In the high-risk cohort undergoing PCI, bivalirudin with provisional GP IIb/IIIa inhibitors achieved better angiographic results. Although not powered to show a difference, and while acknowledging that a selection bias could have affected the data, the present study showed that bivalirudin may be as clinically effective and safe as heparin with adjunctive GP IIb/IIIa inhibitors.     

Effect of bivalirudin on coagulation function and prognosis in patients with coronary artery disease and renal insufficiency undergoing PCI

Background Renal insufficiency is associated with an excess risk of vascular complications and bleeding events in patients who undergo PCI. Heparin is still used commonly for PCI, but the bleeding complications is high. However, Bivalirudin is similar to heparin in ischemic complications and superior to the bleeding complications. Methods A total of 181 patients with coronary artery disease and renal insufficiency were randomly assigned two treatment groups: Bivalirudin(n = 90), unfractionated heparin(n = 91). Activated clotting time(ACT)was determined in patients at 5 min after undergoing PCI at the end of operation immediately(stopping drug immediately), and 30 min,1 h, 2 h after stopping drug. Activated partial thromboplastin time(APTT), thrombin time(TT), proth rombin time(PT), fibrinogen(FIB) index were measured before treatment, 6 h, 24 h and 72 h after the treatment through an automated coagulation analyzer. Platelet count was monitored before treatment and24 h after treatment. The end points were the proportion of net adverse clinical events(NACE)and stent thrombosis at 30 days. Results The use of bivalirudin was associated with a statistically significant higher at 5 min after treatment, end of operation immediately(P 0.05),with statistically significant lower at 1h after stopping drug, 2h after stopping drug(P 0.05). There were no differences between patients at blood coagulation and platelet after operation(P 0.05), no differences in the 30-day rates of stent thrombosis(0% vs. 0%, P = 1). Eleven patients(12.22%) treated with bivalirudin vs. 24(26.38%) treated with heparin experienced an adverse clinical events at 30 days(relative risk[RR], 0.46; 95%CI, 0.36-0.56; P 0.025). There were no differences in the major adverse cardiac or cerebral event at the 30-day end point(1.11% vs. 2.20%, P 0.05). The bleeding at 30 days was abated by using bivalirudin compared with unfractionated heparin(11.11% vs. 24.18%, P 0.05). Conclusions Compared with the unfractionated heparin, bivalirudin is more quickly in taking effect and recovering and more efficient for PCI in patients with coronary artery disease and renal insufficiency.     

Bivalirudin: Pharmacology and Clinical Applications

Bivalirudin (Hirulog®, Angiomax®) is a specific, reversible and direct thrombin inhibitor with a predictable anticoagulant effect. It is cleared by both proteolytic cleavage and renal mechanisms, predominantly glomerular filtration. Bivalirudin inhibits both circulating thrombin and fibrin bound thrombin directly by binding to thrombin catalytic site and anion‐binding exosite I in a concentration‐dependent manner. Bivalirudin prolongs activated partial thromboplastin time, prothrombin time, thrombin time and activated clotting time (ACT). ACT levels with bivalirudin do not correlate with its clinical efficacy. Bivalirudin with a provisional GpIIb/IIIa inhibitor is indicated in elective contemporary percutaneous coronary intervention (PCI). In respect to combined ischemic and hemor‐rhagic endpoints of death, myocardial infarction, unplanned urgent revascularization and major bleeding during PCI (including subgroups of patients with renal impairment and diabetes) bivalirudin is not inferior to unfractioned heparin and planned GpIIb/IIIa inhibitors. In addition, bivalirudin has been consistently shown to have significantly less in‐hospital major bleeding than heparin alone or heparin in combination with‐a GpIIb/IIIa inhibitor. Bivalirudin appears to be also safe and effective during PCI in patients with heparin‐induced thrombocytopenia. Finally, data from PCI studies support the safety and efficacy of bivalirudin, although its direct randomized comparison with unfractionated heparin is lacking.     

Évaluations clinique et économique de la bivalirudine au cours des procédures d’angioplasties coronaires

Bivalirudin, with provisional GP IIb/IIIa inhibitor use allows the same protection against ischemic complications while reducing the hemorrhagic complications compared with the systematic association of a GP IIb/IIIa inhibitor plus heparin (The Randomized Evaluation in PCI Linking Angiomax to Reduced Clinical Events-2 [Replace-2]). In clinical practice, the use of heparin is not systematically associated with a GP IIb/IIIa inhibitor. That's why we studied the clinical and economic interest of bivalirudin only versus heparin (UFH) only. Opened pragmatic monocentric study carried out in 2007. We made a chronological matching: for each patient treated with bivalirudin, we included the next patient with the same clinical presentation treated with unfractionated heparin. Ninety-two patients were included (46 in each group). The need for a GP IIb/IIIa inhibitor during the PCI was not significantly different between the two groups (p = 0.11). No major hemorrhagic complications were observed in the two groups. Prevalence of ecchymosis was not significantly different: 22 % in the UFH group versus 13 % in the bivalirudin group (p = 0.27). The average troponin level the next day was significantly higher in the bivalirudin group (p = 0,049), although the change in troponin levels before and after the procedure was similar in the two groups. The average cost by patient of anticoagulation by bivalirudin and HNF is very different, respectively 473 ± 150 and 51 ± 146 € (p = 0.0001). Bivalirudin can be an interesting alternative for patients with a high risk of having complications. But considering its cost this therapy must be used only for selected patients.     

国产注射用比伐卢定和肝素在冠状动脉介入治疗术中对血小板功能的影响

目的:探讨国产注射用比伐卢定和肝素在经皮冠状动脉介入治疗(PCI)术中对血小板功能的影响. 方法:选择36例择期行PCI的患者,术中用肝素(肝索组,n=18)或国产注射用比伐卢定(比伐卢定组,n=18)抗凝.分别在用药前、用药后10 min、用药结束、用药结束后30 min、用药结束后2 h静脉采血,检测二磷酸腺苷诱导的血小板最大聚集率和血浆P选择素水平. 结果:肝素组患者用药后血小板最大聚集率及血浆P选择索水平升高,用药后10 min与用药前比较,差异均有统计学意义(P均<0.05),其余各时间点与用药前比较,差异均无统计学意义(P均>0.05).比伐卢定组患者血小板最大聚集率及血浆P选择素水平,用药后10 min及用药结束与用药前比较均降低(P均<0.05),差异均有统计学意义;用药结束后30 min与用药前比较,差异无统计学意义(P>0.05). 结论:与常规肝素抗凝相比,国产注射用比伐卢定作为抗凝剂应用于PCI术中可以短时间内降低血小板活性、抑制血小板聚集,具有暂时性抗血小板的功能.     

Comparison of platelet function and morphology in patients undergoing percutaneous coronary intervention receiving bivalirudin versus unfractionated heparin versus clopidogrel pretreatment and bivalirudin

We hypothesized that direct thrombin inhibition could attenuate platelet activation and release of soluble CD40 ligand (sCD40L), a marker of inflammation, during percutaneous coronary intervention (PCI). To assess platelet function under flow conditions with bivalirudin versus unfractionated heparin (UFH), we employed the cone and plate(let) analyzer (CPA) assay in drug-spiked blood samples from volunteers (n = 3) in vitro, and then in PCI patients who received bivalirudin alone (n = 20), UFH alone (n = 15), and clopidogrel pretreatment plus bivalirudin (n = 15). Scanning electron microscopy was employed to image bivalirudin or UFH-treated platelets to determine whether platelet function observations had a morphologic explanation. Enzyme immunoassay was used to measure sCD40L levels in PCI patients. In vitro, bivalirudin decreased platelet surface coverage; UFH increased platelet surface coverage. In PCI patients, bivalirudin alone decreased platelet surface coverage, UFH alone increased platelet surface coverage, and clopidogrel pretreatment plus bivalirudin additively reduced platelet surface coverage. Unlike UFH, bivalirudin did not activate platelets in SEM studies. Bivalirudin alone or coupled with clopidogrel significantly reduced plasma sCD40L in PCI patients. In conclusion, our findings suggest that under flow conditions, bivalirudin alone or coupled with clopidogrel may have an antiplatelet effect versus UFH alone during PCI. These data suggest that bivalirudin and UFH may confer an anti-inflammatory effect by reducing sCD40L during PCI.