What is Bivalirudin (Angiomax)?

From the Guidelines

Bivalirudin is a direct thrombin inhibitor medication primarily used as an anticoagulant during procedures like percutaneous coronary intervention (PCI) and in patients with heparin-induced thrombocytopenia, with a recommended dose of 0.75 mg/kg intravenous bolus followed by a 1.75 mg/kg/hour infusion during the procedure, as supported by the 2020 ESC guidelines 1. The medication works by binding directly to thrombin, preventing the conversion of fibrinogen to fibrin and thus inhibiting blood clot formation.

• The typical dose for PCI is a 0.75 mg/kg intravenous bolus followed by a 1.75 mg/kg/hour infusion during the procedure.
• Bivalirudin has a short half-life of about 25 minutes, allowing for quick offset of action when the infusion is stopped.
• This medication requires dose adjustment in patients with renal impairment since it's primarily eliminated by the kidneys.
• Compared to heparin, bivalirudin may offer advantages including more predictable anticoagulation, less binding to plasma proteins, and potentially lower bleeding risk in certain patient populations, as seen in the REPLACE 2 trial 1.
• Common side effects include bleeding, back pain, nausea, headache, and hypotension.
• Regular monitoring of activated clotting time (ACT) is recommended during treatment to ensure appropriate anticoagulation levels. The use of bivalirudin has been evaluated in several studies, including the ACUITY trial, which showed that bivalirudin alone compared with heparin plus GP IIb/IIIa inhibitors resulted in noninferior rates of composite ischemia and significantly reduced major bleeding 1.
• The ACUITY trial used a 2x2 factorial design to compare a heparin with or without upstream GP IIb/IIIa inhibition versus bivalirudin with or without upstream GP IIb/IIIa inhibition.
• The study was randomized but open-label, and the main comparisons were of heparin with GP IIb/IIIa inhibition versus bivalirudin with GP IIb/IIIa inhibition versus bivalirudin with provisional GP IIb/IIIa inhibition. However, the Writing Committee notes that the use of bivalirudin alone may introduce a note of caution, especially when there is a delay to angiography or if early ischemic discomfort occurs after the initial antithrombotic strategy has been implemented 1.
• The 2020 ESC guidelines recommend bivalirudin as an alternative to UFH plus GP IIb/IIIa inhibitors during PCI, with a dose of 0.75 mg/kg i.v. bolus, followed by 1.75 mg/kg/h for up to 4 h after the procedure 1.

From the FDA Drug Label

Bivalirudin Injection contains bivalirudin trifluoroacetate, which is a specific and reversible direct thrombin inhibitor Bivalirudin trifluoroacetate is a synthetic, 20 amino acid peptide salt, with the chemical name of D-phenylalanyl-L-prolyl-L-arginyl-L-prolylglycylglycylglycylglycyl-L-asparagylglycyl-L-α-aspartyl-L-phenylalanyl-L-α-glutamyl-L-α-glutamyl-L-isoleucyl-L-prolyl-L-α-glutamyl-L-α-glutamyl-L-tyrosyl-L-leucine trifluoroacetate. Bivalirudin is a direct thrombin inhibitor and an anticoagulant used in patients undergoing percutaneous coronary intervention (PCI) 2, 2.

• It works by inhibiting thrombin, a key enzyme in the coagulation process.
• The drug is administered intravenously and is available in a ready-to-use solution 2.

From the Research

Definition and Mechanism of Bivalirudin

• Bivalirudin is a direct thrombin inhibitor (DTI) used for anticoagulation in invasive cardiology, particularly percutaneous coronary intervention (PCI) 3, 4, 5.
• It is a 20 amino acid polypeptide hirudin analog that displays bivalent and reversible binding to the thrombin molecule, inhibiting its action 4, 5.
• Bivalirudin has a unique pharmacologic profile, undergoing predominant non-organ elimination (proteolysis) and having a short half-life of approximately 25 minutes 3.

Clinical Uses of Bivalirudin

• Bivalirudin is primarily used for anticoagulation during percutaneous transluminal coronary angioplasty (PTCA) and PCI, with or without glycoprotein IIb/IIIa antagonist therapy 3, 5, 6.
• It is also indicated for patients with or at risk of heparin-induced thrombocytopenia (HIT) or HIT with thrombosis syndrome (HITTS) undergoing PCI 3.
• Bivalirudin has been shown to be effective in reducing bleeding complications compared to heparin plus glycoprotein IIb/IIIa inhibitors in patients undergoing PCI 5, 7.

Efficacy and Safety of Bivalirudin

• Clinical trials have demonstrated that bivalirudin is a viable alternative to heparin combined with a glycoprotein IIb/IIIa inhibitor in patients undergoing PCI 4, 5, 7.
• Bivalirudin has been shown to reduce the risk of major bleeding complications compared to heparin plus glycoprotein IIb/IIIa inhibitors, while maintaining similar efficacy in preventing ischemic events 5, 7.
• The ACUITY trial demonstrated that bivalirudin alone or with glycoprotein IIb/IIIa inhibitors is effective in patients with acute coronary syndromes undergoing PCI, with a reduced risk of major bleeding complications 7.