Bivalirudin: The relevance in today's interventional practice

Jacc-cardiovascular Interventions, 2011

Objectives The aim of this study was to evaluate the relative frequency of access and nonaccess site bleeding, the association of these events with 1-year mortality, and the impact of randomized antithrombotic therapy.

Journal of the American College of Cardiology, 2012

The purpose of this study was to examine temporal trends in post-percutaneous coronary intervention (PCI) bleeding among patients with elective PCI, unstable angina (UA)/non-ST-segment elevation myocardial infarction (NSTEMI), and ST-segment elevation myocardial infarction (STEMI).

Vascular Health and Risk Management, 2011

The advent of potent antiplatelet and antithrombotic agents over the past decade has resulted in significant improvement in reducing ischemic events in acute coronary syndrome (ACS). However, the use of antiplatelet and antithrombotic combination therapy, often in the settings of percutaneous coronary intervention (PCI), has led to an increase in the risk of bleeding. In patients with non-ST elevation myocardial infarction treated with antithrombotic agents, bleeding has been reported to occur in 0.4%-10% of patients, whereas in patients undergoing PCI, periprocedural bleeding occurs in 2.2%-14% of cases. Until recently, bleeding was considered an intrinsic risk of antithrombotic therapy, and efforts to reduce bleeding have received little attention. There have been increasing data demonstrating that bleeding is associated with adverse outcomes, including myocardial infarction, stroke, and death. Therefore, it is imperative to optimize patient outcomes by adopting pharmacological and nonpharmacological strategies to minimize bleeding while maximizing treatment efficacy. In this paper, we present a review of the bleeding classifications used in large-scale clinical trials in patients with ACS and those undergoing PCI treated with antiplatelets and antithrombotic agents, adverse outcomes, particularly mortality associated with bleeding complications, and suggested predictive risk factors. Potential mechanisms of the association between bleeding and mortality and strategies to reduce bleeding complications are also discussed.

2009

The American Journal of Cardiology, 2008

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.

Canadian Journal of Cardiology, 2009

Therapeutic advances in cardiovascular disease, 2011

J Am Coll Cardiology, 2018

BACKGROUND Contrasting evidence exists on the comparative efficacy and safety of bivalirudin and unfractionated heparin (UFH) in relation to the planned use of glycoprotein IIb/IIIa inhibitors (GPIs). OBJECTIVES This study assessed the efficacy and safety of bivalirudin compared with UFH with or without GPIs in patients with acute coronary syndrome (ACS) who underwent invasive management. METHODS In the MATRIX (Minimizing Adverse Haemorrhagic Events by Transradial Access Site and Systemic Implementation of AngioX) program, 7,213 patients were randomly assigned to receive either bivalirudin or UFH with or without GPIs at discretion of the operator. The 30-day coprimary outcomes were major adverse cardiovascular events (MACEs) (a composite of death, myocardial infarction, or stroke), and net adverse clinical events (NACEs) (a composite of MACEs or major bleeding). RESULTS Among 3,603 patients assigned to receive UFH, 781 (21.7%) underwent planned treatment with GPI before coronary intervention. Bailout use of GPIs was similar between the bivalirudin and UFH groups (4.5% and 5.4%) (p ¼ 0.11). At 30 days, the 2 coprimary endpoints of MACEs and NACEs, as well as individual endpoints of mortality, myocardial infarction, stent thrombosis or stroke did not differ among the 3 groups after adjustment. Compared with the UFH and UFHþGPI groups, bivalirudin reduced bleeding, mainly the most severe bleeds, including fatal and nonaccess siteÀrelated events, as well as transfusion rates and the need for surgical access site repair. These findings were not influenced by the administered intraprocedural dose of UFH and were confirmed at multiple sensitivity analyses, including the randomly allocated access site. CONCLUSIONS In patients with ACS, the rates of MACEs and NACEs were not significantly lower with bivalirudin than with UFH, irrespective of planned GPI use. However, bivalirudin significantly reduced bleeding complications, mainly those not related to access site, irrespective of planned use of GPIs. (Minimizing Adverse Haemorrhagic Events by Transradial Access Site and Systemic Implementation of AngioX [MATRIX]; NCT01433627)

Journal of Thrombosis and Thrombolysis, 2004

Background: Pharmacoinvasive therapy for the treatment of ST elevation myocardial infarction (STEMI) is a strategy that combines early restoration of coronary flow via pharmacologically induced thrombolysis with subsequent, prompt percutaneous coronary intervention (PCI). Prior studies suggesting a heightened bleeding risk of PCI performed early after fibrinolysis predated contemporary pharmacoinvasive practice including use of femoral closure devices (CD), fibrin specific thrombolytics, lower doses of heparin and stents. Methods: Consecutive patients were included in this retrospective registry study if they underwent emergent PCI for ST elevation myocardial infarction (STEMI) followed by immediate use of a groin closure device. Between Oct 1, 2002 and Jan 1, 2003, 27 patients were treated with immediate use of CD after post-thrombolytic PCI, performed within 12 hours of thrombolysis (pharmacoinvasive group). 58 patients were treated with immediate use of CD after primary PCI for STEMI. The two groups were compared with respect to the incidence of successful groin closure, bleeding complications, and clinical outcomes. Bleeding events were categorized according to the TIMI criteria. All baseline clinical and treatment variables were compared between the two groups to determine and the association of these variables (including use of thromblytic therapy) with TIMI major and TIMI minor bleeding was determined. Results: Pharmacoinvasive recanalization with PCI occurred 348 ± 183 minutes after initiation of fibrinolytic therapy. Glycoprotein IIb/IIIa inhibitors were used less frequently in the patients treated with a thrombolytic agent (59% vs. 90%, p p = 0.89). No patient required vascular surgical intervention. TIMI major bleeding and transfusion requirements were less than 5% in both groups. Antecedent thrombolytic therapy was not a predictor of bleeding complications after PCI. Conclusions: Use of CD as part of a contemporary pharmacoinvasive strategy is associated with a low rate of major bleeding complications.

2010

In patients undergoing percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS), both periprocedural acute myocardial infarction and bleeding complications have been shown to be associated with early and late mortality. Current standard antithrombotic therapy after coronary stent implantation consists of lifelong aspirin and clopidogrel for a variable period depending in part on the stent type. Despite its well-established efficacy in reducing cardiac-related death, myocardial infarction, and stroke, dual antiplatelet therapy with aspirin and clopidogrel is not without shortcomings. While clopidogrel may be of little beneficial effect if administered immediately prior to PCI and may even increase major bleeding risk if coronary artery bypass grafting is anticipated, early discontinuation of the drug may result in insufficient antiplatelet coverage with thrombotic complications. Optimal and rapid inhibition of platelet activity to suppress ischemic and thrombotic events while minimizing bleeding complications is an important therapeutic goal in the management of patients undergoing percutaneous coronary intervention. In this article we present an overview of the literature on clinical trials evaluating the different aspects of antithrombotic therapy in patients undergoing PCI and discuss the emerging role of these agents in the contemporary era of early invasive coronary intervention. Clinical trial acronyms and their full names are provided in Table 1.