Bivalirudin: Overview, Pharmacology and Clinical Applications

General Description

Bivalirudin, a direct thrombin inhibitor with unique pharmacological properties, is widely used in invasive cardiology for its efficacy in preventing blood clot formation during procedures. Derived from hirudin, it binds transiently to thrombin, offering control over anticoagulation therapy duration. Its reversible binding mechanism and rapid clearance reduce bleeding risks. Clinically, bivalirudin is crucial in percutaneous coronary interventions, especially for patients with or at risk of heparin-induced thrombocytopenia. It also shows promise in acute coronary syndrome and myocardial infarction management, cardiac surgery, and treating acute HIT. Overall, bivalirudin presents a valuable alternative to heparin in various cardiovascular settings.

Figure 1. Bivalirudin

Overview

Bivalirudin is a direct thrombin inhibitor that is commonly employed as an anticoagulant in invasive cardiology procedures. Unlike other available direct thrombin inhibitors like lepirudin, argatroban, and desirudin, which have specific uses such as treating heparin-induced thrombocytopenia or post-orthopedic surgery thromboprophylaxis, bivalirudin has found widespread use in mainstream invasive cardiology. As a direct thrombin inhibitor, bivalirudin directly inhibits the activity of thrombin, an enzyme crucial for blood clot formation. By blocking thrombin, bivalirudin helps prevent the formation of harmful blood clots during invasive cardiology procedures, reducing the risk of complications such as myocardial infarction or stroke. Bivalirudin's popularity in invasive cardiology stems from its favorable pharmacologica profile and clinical efficacy. It has a relatively short half-life, allowing for rapid clearance from the body, which provides clinicians with greater control over the duration of anticoagulation therapy. Additionally, bivalirudin has a reversible binding mechanism with thrombin, making it easier to manage potential bleeding complications compared to other anticoagulants. ¹

Pharmacology

Bivalirudin is a pharmacological agent commonly known as Angiomax, used for its anticoagulant properties. It is an oligopeptide analogue of hirudin, a naturally occurring peptide found in leech saliva. Bivalirudin is smaller in size compared to hirudin, consisting of a 12-amino acid segment derived from hirudin and a tetrapeptide sequence at its amino-terminus, connected by four glycine residues. One of the key features of bivalirudin is its ability to specifically bind to thrombin at two sites without the need for a cofactor. While hirudin's binding to thrombin is irreversible, bivalirudin's binding is transient. It has an intermediate affinity for thrombin, with a Ki value of 2 nM for human thrombin. This makes it more potent than argatroban but less potent than hirudin. Unlike heparin, bivalirudin inhibits thrombin regardless of whether it is free or bound to fibrin. Additionally, bivalirudin has a low immunogenic potential compared to heparin, which is a significant drawback of heparin therapy. The drug is predominantly eliminated through proteolysis rather than organ mechanisms, with only a minor portion undergoing renal clearance. When administered intravenously, bivalirudin produces a rapid anticoagulant effect. Its clearance rate exceeds the glomerular filtration rate, indicating dual clearance through proteolysis and kidneys. The half-life of bivalirudin is approximately 25 minutes, shorter than other marketed direct thrombin inhibitors like argatroban and lepirudin. Monitoring of bivalirudin's anticoagulant effects can be done through various clotting assays such as prothrombin time (PT)/international normalized ratio (INR), activated clotting time (ACT), and activated partial thromboplastin time (APTT). The drug's effects reverse rapidly upon discontinuation, with coagulation times returning to baseline within 1 to 2 hours. It is important to adjust the dosing and monitoring of bivalirudin in patients with renal insufficiency, as the drug's half-life is prolonged in severe renal dysfunction. Patients undergoing dialysis require lower initial doses and more frequent monitoring. Overall, bivalirudin's pharmacological profile makes it a valuable anticoagulant option, particularly in situations where heparin therapy is contraindicated or associated with a higher risk of immune-mediated complications. ²

Clinical applications

Bivalirudin, an anticoagulant, has various clinical applications. Its primary use is for anticoagulation during percutaneous transluminal coronary angioplasty (PTCA), a common procedure in percutaneous coronary intervention (PCI). It is also indicated for PCI with provisional use of glycoprotein (GP) IIb/IIIa antagonist therapy and for patients with or at risk of heparin-induced thrombocytopenia (HIT) undergoing PCI. In Canada, it is also approved for HIT patients undergoing cardiac surgery. Bivalirudin has been evaluated for non-interventional treatment of acute coronary syndrome (ACS) and myocardial infarction (MI), as well as for anticoagulation during cardiac surgery when heparin is contraindicated. It can be used for both routine and off-pump cardiac surgery. Additionally, bivalirudin is effective in treating acute HIT, including specialized situations such as cardiac surgery and PCI. It's important to note that this discussion focuses on the efficacy of bivalirudin in PTCA and other PCI procedures, along with off-label uses in ACS/MI and cardiac surgery. Other clinical situations, such as non-interventional treatment of ACS/MI, peripheral percutaneous interventions (PPI), and prevention/treatment of venous thromboembolism, will not be covered in this section. ²

Reference

1. Ryerson LM, McMichael ABV. Bivalirudin in pediatric extracorporeal membrane oxygenation. Curr Opin Pediatr. 2022;34(3):255-260.

2. Warkentin TE, Greinacher A, Koster A. Bivalirudin. Thromb Haemost. 2008;99(5):830-839.

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