Bivalirudin
Also known as: Angiomax, Angiox, Hirulog, bivalirudin sodium, direct thrombin inhibitor (DTI), 20-amino-acid hirudin analogue
Direct thrombin inhibitor (DTI) — synthetic bivalent 20-amino-acid peptide; parenteral anticoagulant
What it is
Bivalirudin (Angiomax/Angiox) is an FDA-approved injectable blood-thinner used during heart procedures and in patients who cannot safely receive heparin. It works by directly blocking thrombin — the key enzyme that causes clotting — providing fast, predictable, and short-lived anticoagulation with a lower risk of serious bleeding than some older alternatives.
The scientific side
bivalirudin is a synthetic 20-amino-acid peptide direct thrombin inhibitor (DTI) that achieves anticoagulation through bivalent, reversible, and direct binding to thrombin without requiring cofactors such as antithrombin. Unlike unfractionated heparin (UFH), which acts indirectly by potentiating antithrombin, bivalirudin binds simultaneously to two distinct sites on the thrombin molecule: the catalytic active site (where the cleavage of fibrinogen occurs) and the anion-binding exosite I (the fibrinogen recognition domain). This dual-site engagement results in potent thrombin inhibition in a concentration-dependent manner. Critically, bivalirudin inhibits both free (circulating) thrombin and clot-bound thrombin — the latter being inaccessible to heparin/antithrombin complexes, representing a mechanistic advantage at the site of active thrombosis. A third element of its pharmacology involves attenuation of collagen-induced platelet activation, giving bivalirudin a triple mechanism: inhibition of plasma thrombin, clot-bound thrombin, and platelet activation at the site of vascular injury. The drug has a short plasma half-life of approximately 25 minutes, making it rapidly titratable and reversible. Its elimination is predominantly proteolytic (non-organ-based cleavage by thrombin itself and other serine proteases), with a secondary renal component (approximately 20% excreted renally), which is pharmacologically important: unlike argatroban (hepatic clearance) or lepirudin (renal clearance), bivalirudin offers a predictable, mixed-clearance profile that confers relative advantage in patients with single-organ impairment. From a pharmacodynamic standpoint, bivalirudin exerts class-specific effects on thrombin generation distinct from UFH: as a selective direct inhibitor, it suppresses thrombin generation less broadly than heparin, which exerts multiple upstream and downstream effects on the coagulation cascade. Bivalirudin prolongs activated partial thromboplastin time (aPTT), activated clotting time (ACT), thrombin time (TT), and prothrombin time (PT/INR), with ACT used as the standard procedural monitoring parameter during PCI. Because its mechanism is independent of antithrombin and plasma protein binding, bivalirudin produces more predictable dose-response kinetics than UFH, particularly in patients with antithrombin deficiency or heparin resistance. (PMIDs: 18449412, 16614733, 31521492, 42102583, 32491755)
Class: Direct thrombin inhibitor (DTI) — synthetic bivalent 20-amino-acid peptide; parenteral anticoagulant
Administration & storage
- Administration
- Intravenous bolus injection followed by continuous IV infusion — the standard procedural anticoagulation routeContinuous IV infusion without a bolus — used in ECMO and CPB settings at lower initiation doses with titration to aPTT or ACT targetAdministration via a dedicated IV line or central venous access is preferred in ICU settings (ECMO/CPB); peripheral IV access is used during PCI procedures
- Storage
- Unreconstituted lyophilized vials: store at 20–25°C (68–77°F); excursions permitted to 15–30°C. Do not freeze. Reconstituted concentrate: store at 2–8°C (refrigerator) for up to 24 hours. Diluted infusion solution: stable for up to 24 hours at room temperature. Do not use if particulate matter is visible or if discolouration is present.
- Cautions
- No reversal agent: unlike heparin (reversed by protamine), there is no specific antidote for bivalirudin. Anticoagulant effect dissipates naturally within ~25–60 minutes after cessation given its short half-life and predominantly proteolytic clearance. Haemostatic support (fresh frozen plasma, platelets) may be required for severe haemorrhage.,Renal dose adjustment required: bivalirudin clearance is partly renal (approximately 20% eliminated unchanged by glomerular filtration). In patients with moderate renal impairment (GFR 30–59 mL/min), the infusion rate should be reduced to 1.0 mg/kg/h. In patients with severe renal impairment (GFR <30 mL/min) or on dialysis, the infusion rate should be reduced to 0.25 mg/kg/h; the bolus dose remains unchanged.,Stent thrombosis risk when infusion is stopped immediately post-PCI: multiple RCTs found increased acute and subacute stent thrombosis with bivalirudin compared to heparin+GPI when the infusion was stopped at the end of the procedure. Post-procedural infusion at full PCI dose reduces this risk substantially.,Coagulation assay interference: bivalirudin prolongs aPTT, ACT, TT, and PT/INR. ACT is used to monitor anticoagulation adequacy during PCI (target 300–350 s). aPTT is used for monitoring in non-PCI settings (ECMO, CPB). Dose-response is more predictable than UFH due to minimal plasma protein binding.
Legal & regulatory status
FDA-approved (NDA 020873 / Angiomax). Approved June 2000 for anticoagulation in patients undergoing percutaneous transluminal coronary angioplasty (PTCA)/PCI. Supplemental approvals: use in patients with, or at risk of,…
Bivalirudin is not included on the current WADA Prohibited List as of 2024–2025. It is a prescription anticoagulant with no known performance-enhancing effect in sport and is not classified under any WADA category…
Approved in Canada as Angiox for anticoagulation in patients undergoing PCI, including those with acute coronary syndromes and patients with HIT or HITTS. Listed as a Schedule F prescription drug administered…
What it's studied for
- Anticoagulation during percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) — NSTEMI and STEMI Phase III RCT (multiple) + meta-analysis
- Anticoagulation in patients with heparin-induced thrombocytopenia (HIT) or HIT with thrombosis syndrome (HITTS) undergoing PCI or cardiac surgery FDA-approved indication + case series / observational
- Anticoagulation during extracorporeal membrane oxygenation (ECMO) as alternative to unfractionated heparin Meta-analysis of observational studies + pilot RCT
- Anticoagulation during cardiopulmonary bypass (CPB) in cardiac surgery — particularly in heparin-resistant or HIT patients Small RCTs + scoping review + case series
- Prevention of stent thrombosis after primary PCI — post-procedural bivalirudin infusion strategy Meta-analysis of RCTs
- Anticoagulation in acute ST-elevation myocardial infarction (STEMI) undergoing primary PCI — HORIZONS-AMI and EUROMAX trial indications Phase III RCT
- Investigational: antiviral and anti-inflammatory activity in respiratory syncytial virus (RSV) infection — preclinical only Preclinical (animal model)
Safety signals
- Major bleeding — reduced versus heparin+GPI but context-dependent versus heparin monotherapy
- Acute and subacute stent thrombosis — increased risk when infusion stopped immediately post-PCI without a prolonged infusion
- No reversal agent — reliance on short half-life for anticoagulation offset
- Renal impairment requiring dose reduction — risk of over-anticoagulation in unrecognized or worsening renal failure
- Coagulation assay interference — prolongs aPTT, ACT, TT, and PT/INR, complicating monitoring
- Hypersensitivity and infusion-related reactions — including reports of anaphylaxis
- Thrombocytopenia and haematological adverse events — distinct from HIT but reported post-marketing
Contraindications
About these dose ranges
Dose ranges below reflect commonly reported community protocols. Where published research cites a specific dose, the PMID is linked. Doses without citations are not clinical recommendations — they reflect what practitioners and researchers commonly report using.
Community-reported dosing
| Route | Dose | Frequency / Duration | Population / context | Source tier |
|---|---|---|---|---|
| Unspecified | IV bolus: 0.75 mg/kg; IV infusion: 1.75 mg/kg/h during procedure | — | Adults undergoing PCI (elective or ACS) — standard procedural dose | Research |
| Unspecified | IV bolus: 0.75 mg/kg; IV infusion: 1.75 mg/kg/h | — | Adults undergoing PCI with HIT or HITTS | Research |
| Unspecified | Variable; typically initiated at 0.03–0.1 mg/kg/h, titrated to aPTT target | — | Adults on ECMO | Research |
| Unspecified | ~2 mg/kg/h IV infusion (with or without bolus); ACT target >400 s or 2.5× baseline | — | Adults undergoing cardiopulmonary bypass for cardiac surgery | Research |
| intravenous | 0.75 mg/kg IV bolus, then 1.75 mg/kg/h IV infusion during procedure; post-procedure full-dose infusion (1.75 mg/kg/h for up to 4 h) to reduce stent thrombosis risk | single procedure; infusion continued during and optionally post-PCI | adults undergoing percutaneous coronary intervention (PCI) for ACS or elective indications, including those with HIT |
No peer-reviewed studies indexed for this peptide yet.