Bivalirudin Research & Studies

Extracorporeal membrane oxygenation (ECMO) is a mechanical support treatment modality used in patients with refractory cardiac and/or pulmonary failure. Bleeding and thrombotic complications associated with ECMO are inherent concerns that require careful management. Anticoagulation optimization may help mitigate these risks by providing more adequate therapeutic anticoagulation and lessen the bleed risk. Heparin, the most used anticoagulant, carries concerns for heparin-induced thrombocytopenia and possible resistance given its dependence on cofactors and circulating proteins to exert its pharmacologic effect. In contrast, bivalirudin, a direct thrombin inhibitor, exerts its effect independent of cofactors or plasma proteins, and possesses thrombin-binding and metabolism features that may confer advantages in ECMO management. This review of the evidence for bivalirudin utilization in ECMO suggests favorable outcomes in circuit-related thrombosis, bleeding, and dosing reliability. In addition, blood product utilization, circuit interventions, and success in ECMO decannulation and survival were positive findings associated with bivalirudin that merit consideration. Common questions and concerns relative to bivalirudin utilization, including laboratory monitoring, utilization in low-flow states, dosing considerations in renal replacement therapy, reversibility, and cost are also discussed in this review. Moreover, this review suggests that bivalirudin utilization presents the opportunity for ECMO management simplification.

Bivalirudin, a bivalent direct thrombin inhibitor, has been developed to reduce bleeding without any trade-off in thrombotic events in acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI).

Bivalirudin (Angiomax, Angiox) is a parenteral direct thrombin inhibitor (DTI) that is used for patients with heparin-induced thrombocytopenia (HIT), where heparin cannot be used due to the risk of thrombosis. Bivalirudin is also licensed for use in cardiology procedures (e.g., percutaneous transluminal coronary angioplasty; PTCA). Bivalirudin is a synthetic analogue of hirudin found in the saliva of the medicinal leech and has a relatively short half-life of ~25 min. Several assays can be used to monitor bivalirudin; these include the activated partial thromboplastin time (APTT), activated clotting time (ACT), ecarin clotting time (ECT), an ecarin-based chromogenic assay, thrombin time (TT), the dilute TT, and the prothrombinase-induced clotting time (PiCT). Drug concentrations can also be measured using liquid chromatography tandem mass spectrometry (LC/MS) and clotting or chromogenic-based assays with specific drug calibrators and controls.

This review summarizes the current literature surrounding the use of bivalirudin as an alternative anticoagulant for pediatric extracorporeal membrane oxygenation (ECMO) patients.

Use of optical coherence tomography (OCT) adds an assessment of thrombus burden remaining on stents after PCI for acute coronary syndromes. Potential variations in stent-related thrombus burden can be documented by OCT as a function of peri-procedural pharmacology supporting the use of OCT in future hypothesis testing. Bivalirudin remains a reliable and expensive alternative to heparin in cases of HIT or patients at high bleeding risk during transfemoral PCI.

Whether heparin, bivalirudin, or bivalirudin delivered on the background of prior heparin therapy, during primary PCI therapy is associated with a better outcome is difficult to ascertain from any one study. Meta-analysis of available trials suggests that the use of bivalirudin on top of prior heparin therapy may be associated with the lowest all-cause mortality and major adverse cardiovascular events while preserving much of the access site bleeding reduction of bivalirudin alone. There may be a role for initial therapy of STEMI with a broad-spectrum anticoagulant such as heparin that is then focused to a more specific direct-thrombin inhibitor (bivalirudin) in primary PCI.

Bivalirudin (Angiomax) is a thrombin-inhibiting oligopeptide that was developed via rational drug design as a hirudin analogue ('hirulog'). Similar to hirudin, it is a bivalent thrombin inhibitor, as its 20-amino acid structure combines a carboxy-terminal region that recognises thrombin's fibrin(ogen)-binding site, and an amino-terminal tetrapeptide that inhibits the active site of thrombin, connected by a tetraglycine spacer. It has certain pharmacological advantages over hirudin, including enzymic metabolism (less dependence on renal clearance) and low immunogenicity (reduced potential for anaphylaxis). Bivalirudin is approved for use in percutaneous transluminal coronary angioplasty (PTCA), and is undergoing active investigation for anticoagulation during cardiac surgery, both 'off-pump' and with cardiopulmonary bypass ('on-pump'). Anecdotal 'off-label' experience for the treatment of heparin-induced thrombocytopenia shows promise.