Evolving role of bivalirudin in percutaneous coronary interventions; impact of the REPLACE-2 study

Percutaneous coronary interventions are being used with increasing frequency nowadays for the treatment of patients with coronary heart disease. Acute thrombotic complications remain one of the major limitations of these procedures for which unfractionated heparin has been the standard foundation anticoagulant. It has, however, many limitations and disadvantages that necessitated research and development of alternative anticoagulant therapies. The direct thrombin inhibitor bivalirudin has been approved as a substitute for heparin in patients undergoing angioplasty for unstable angina based on data in higher-risk patients where bivalirudin resulted in lower rates of ischaemic and bleeding complications compared to heparin. This evidence was collected prior to the widespread use of platelet glycoprotein (GP) IIb/IIIa receptor blockers, thienopyridines and intracoronary stents, considered standard practice for such patients today. The REPLACE-2 study was carried out to establish whether, in the current era, bivalirudin used with provisional GP IIb/IIIa blockade if necessary during the procedure could provide equivalent protection from ischaemic events compared with the gold standard of heparin plus routine GP IIb/IIIa blockade. With advantages with regards to bleeding, ease of use and reduced cost, bivalirudin use with provisional GP IIb/IIIa inhibitors in low-to-moderate risk percutaneous coronary interventions allows GP IIb/IIIa receptor antagonists to be used in a selective fashion, rather than in all patients. In this article, background rationale for bivalirudin use in this setting is reviewed as well as past research in this area. Additionally, the implications of the REPLACE-2 study in establishing where bivalirudin fits into our current interventional cardiology practice and future directions are presented.     

比较国产比伐卢定与肝素对大鼠颈总动脉血栓模型凝血系统的影响

目的比较国产比伐卢定（bivalirudin,B）与肝素（heparin,H）对大鼠颈总动脉血栓模型凝血系统的影响。方法以50％FeCl3诱导大鼠左颈总动脉血栓形成建立模型。42只SD大鼠分为假手术组（S组,n=6）、血栓模型组（M组,n=12）、国产比伐卢定联合尿激酶（urokinase,UK）组（B＆UK组,n=12）、肝素联合UK组（H＆UK组,n=12）,观察4组给药前与用药后2h活化部分凝血活酶时间（activated partial thromboplastin time,APTT）、凝血酶原时间（prothrombin time,PT）及血栓质量的变化。结果与S组比较,M组、B＆UK组及H＆UK组给药前APTT、PT均缩短,但后3组间比较差异无统计学意义（P〉0．05）;与S组比较,给药后M组APTT、PT明显缩短：与S组及M组比较,给药后B＆UK组及H＆UK组APTT、PT均明显延长（P〈0．01）,而H＆UK组APTT比B＆UK组显著延长,相反,B＆UK组盯比H＆UK组显著延长。S组血管内无血栓形成．B＆UK组及H＆UK组血栓质量均显著低于M组[（2．14±0．40）mg比（3．28±0．58）mg,（2．41±0．58）mg比（3．28±0．58）mg,P均〈0．01]。结论国产比伐卢定与肝素均能在大鼠UK溶栓过程中发挥抗凝及抑制血栓形成作用,且国产比伐卢定比肝素抑制外源性凝血系统的作用更明显,能更有效减少出血风险。     

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.     

Bivalirudin in patients undergoing percutaneous coronary intervention and independent predictors of postoperative adverse events in these patients: A real world retrospective study

The efficacy and safety of bivalirudin in percutaneous coronary intervention (PCI) has always been a hot topic in perioperative antithrombotic therapy, but there are still some controversies. So studies are needed to provide more evidence, especially the real world study which includes patients excluded from previous RCT studys. Our study aimed to investigate these information and analyze the independent predictors of postoperative adverse events.A retrospective study enrolled 1416 patients underwent PCI in Tianjin Chest Hospital from May 2016 to October 2017. The incidence of stent-thrombosis and net clinical adverse events, including all-cause death, myocardial infarction, stroke, urgent target-vessel revascularization and bleeding, were followed up for 30 days and 1 year. Logistic regression and COX regression were respectively used to analyze independent predictors of bleeding events within 30-days, and independent predictors of Major adverse cardiovascular and cerebrovascular events (MACCE) in patients with stent implantation within 1-year.Seven hundred six patients were treated with bivalirudin while 710 with unfractionated heparin (UFH). The proportions of diabetes, hypertension, anemia, myocardial-infarction history, PCI history, moderate-to-severe renal-impairment, gastrointestinal-bleeding history in the bivalirudin group were significantly higher (P < .05). Women, anemia were independent risk factors for bleeding within 30-days (P < .05). Among 682 patients with stent implantation in bivalirudin group, anemia, Body Mass Index (BMI) >25 kg/m², KILLIP ≥2, ejection fraction (EF) <45%, eGFR <60 ml/minutes were independent risk factors for MACCE, while Statins, proton pump inhibitor (PPI) were independent protective factors for MACCE with-in 1-year (P < .05).Bivalirudin have good anticoagulant effect and lower bleeding risk during PCI, especially in patients with higher bleeding risk. In patients treated with bivalirudin, female, anemia were independent predictors of bleeding within 30-days, BMI >25 kg/m², anemia, KILLIP ≥2, EF <45%, eGFR <60 ml/minutes were independent risk factors and Statins, PPI were independent protective factors of MACCE within 1-year.     

Antithrombotic therapy following transcatheter aortic valve implantation: what challenge do we face?

The issue of stroke and bleeding events following transcatheter aortic valve implantation (TAVI) and its relation with antithrombotic regimens before, during and after the procedure is increasingly recognized as an important issue. While dedicated trials are ongoing, there is no clear evidence at present on the best antithrombotic regimen in the context of TAVI. In this article, we will go through the mechanisms involved in embolic and bleeding complications of TAVI, and we will discuss the key aspects of antithrombotic treatment in patients undergoing TAVI.