Bottom line
Bivalirudin is a synthetic 20-amino-acid bivalent direct thrombin inhibitor that binds reversibly to both the active site and exosite 1 of thrombin. FDA-approved for PCI with provisional use of GPI and for patients with heparin-induced thrombocytopenia (HIT/HITTS) undergoing PCI. In the EU, the Angiox marketing authorization was withdrawn in 2018 at the MAH's request. Compared with heparin+GPI in the REPLACE-2 trial, bivalirudin+GPI-provisional showed similar ischemic outcomes with less major bleeding.
Identity and composition
| Field | Verified information |
|---|---|
| Preferred name | Bivalirudin |
| Key aliases | Angiomax, Angiox, bivalirudin trifluoroacetate |
| Molecular/sequence identity | 20-amino-acid synthetic linear peptide; sequence: D-Phe-Pro-Arg-Pro-Gly-Gly-Gly-Gly-Asn-Gly-Asp-Phe-Glu-Glu-Ile-Pro-Glu-Glu-Tyr-Leu (amino to carboxy). Approximates the N-terminal fragment of hirudin. |
| Modifications/form | D-Phe at N-terminus; trifluoroacetate salt; lyophilized powder for IV administration after reconstitution |
| Stable identifiers | PubChem CID: 16129704 (bivalirudin); DrugBank: DB00006; ChEBI: CHEBI:59156; CAS: 128270-60-0 |
| Identity caveats | A synthetic analogue of the hirudin C-terminal and N-terminal domains; not identical to natural hirudin |
Development and approval status
| Jurisdiction | Status and indication | Product/source | As of |
|---|---|---|---|
| USA (FDA) | Approved — anticoagulant in PCI (with provisional GPI), including HIT/HITTS patients | Angiomax (The Medicines Company) | 2000 |
| EU (EMA) | Approved 2004; marketing authorization withdrawn 2018 | Angiox (Nycomed/Medicines Company) | 2004–2018 |
| UK (MHRA) | Approved historically; marketing authorization withdrawn 2018 | Angiox | 2004–2018 |
Mechanism and pharmacology
Bivalirudin directly and reversibly inhibits thrombin by binding to both the catalytic (active) site and the fibrinogen-binding exosite (anion-binding exosite 1) on circulating and clot-bound thrombin. Unlike heparin, bivalirudin does not require antithrombin III as a cofactor and is not neutralized by platelet factor 4 (no HIT risk).
Pharmacokinetics: IV bolus onset immediate; half-life ~25 min; primarily proteolytic cleavage (not renal for clearance of activity, though renal excretion of intact peptide occurs); 20-25% unchanged in urine. Dose adjustment for severe renal impairment on contemporary labels.
Evidence by claim
| Claim/indication | Stage | Grade | Best human evidence | Main result | Important limitations |
|---|---|---|---|---|---|
| PCI (with provisional GPI) | Approved | A | REPLACE-2 (N=6,002; DB, RCT) | Composite death/MI/urgent revascularization at 30 d: 7.6% (bivalirudin+provisional GPI) vs 7.1% (heparin+GPI); major bleeding: 2.4% vs 4.1% (p less than 0.001) | Non-inferiority design; 7.2% of bivalirudin arm received GPI provisionally |
| Unstable angina/PTCA | Approved (original) | A | BAT (2 identical trials; N=4,312; DB, RCT) | Procedural failure: 7.9% (bivalirudin) vs 9.3% (heparin); major hemorrhage: 3.5% vs 9.3% | Did not demonstrate statistical superiority for ischemic endpoints; bleeding benefit was significant |
| HIT/HITTS undergoing PCI | Approved | B | AT-BAT (N=51; single-arm, open-label) | Adequate ACT achieved; no major bleeding; 2/51 developed thrombocytopenia | Small, uncontrolled; no active comparator |
Key studies
| Study | Design/population | Exposure studied | Endpoints and result | Limitations |
|---|---|---|---|---|
| REPLACE-2 | DB, RCT; N=6,002; PCI patients | Bivalirudin 0.75 mg/kg bolus + 1.75 mg/kg/h infusion vs heparin 65 IU/kg + planned GPI | 30-d death/MI/urgent revascularization: 7.6% vs 7.1% (non-inferior); major bleeding: 2.4% vs 4.1% (p less than 0.001) | Provisional GPI rate higher than some subsequent practice |
| BAT (combined) | DB, RCT; N=4,312; unstable angina/PTCA | Bivalirudin 1 mg/kg bolus + 2.5 mg/kg/h × 4 h + 0.2 mg/kg/h × 14-20 h vs heparin | 7-d composite: similar between groups; major hemorrhage: 3.5% vs 9.3% (p less than 0.001) | Dosing differs from current PCI regimen |
| AT-BAT | Single-arm, open-label; N=51; HIT/HITTS patients | Bivalirudin 1 mg/kg + 2.5 mg/kg/h or 0.75 mg/kg + 1.75 mg/kg/h | No major bleeding; adequate anticoagulation | Uncontrolled; small sample |
Dose and administration evidence
Approved labeled regimen
The label summary below is product-, indication-, and jurisdiction-specific; consult the full current label and a licensed clinician/pharmacist.
PCI: 0.75 mg/kg IV bolus, immediately followed by 1.75 mg/kg/h IV infusion for the procedure duration and up to 4 h post-procedure. Continue at 0.2 mg/kg/h for up to 20 h if needed. Reduce infusion to 1.0 mg/kg/h in severe renal impairment (CrCl less than 30 mL/min). Use with aspirin 300-325 mg daily.
Studied regimens (not recommendations)
BAT regimen (1 mg/kg bolus + 2.5/0.2 mg/kg/h infusion) is not the current PCI-recommended dose.
What is not established
ACS patients not undergoing PCI (limitation of use per label).
Coronary artery bypass grafting (studied but not labeled; associated with higher rates of bypass-graft occlusion in some studies).
Pediatric use: not established.
Safety
Established label risks
Bleeding (most common adverse event). Major bleeding 4.0% (Angiomax vs heparin+GPIIb/IIIa) in REPLACE-2; similar to comparator. Intracranial, retroperitoneal, hemoglobin drop >3 g/dL, or transfusion ≥2 units.
Hemorrhage risk increased with concurrent antiplatelet agents, other anticoagulants, thrombolytics.
Allergic reactions: rare; anaphylaxis and hypersensitivity have been reported including urticaria, hypotension, dyspnea.
Thrombocytopenia: reported but incidence similar to comparator. No direct HIT risk (does not interact with platelet factor 4).
Thrombosis (catheter-associated, coronary).
Coronary artery dissection, vessel perforation, pseudoaneurysm.
No boxed warning for neuraxial hematoma — bivalirudin's short half-life and mechanism do not carry the same neuraxial anesthesia warning as LMWH/factor Xa inhibitors.
Human-study signals
Increased ischemic events (death, MI) in patients with STEMI undergoing primary PCI treated with bivalirudin vs heparin in contemporary trials (HEAT-PPCI, MATRIX) — attributable to trial design differences (operator blinding, concurrent antiplatelet use) rather than the drug itself.
Unknowns and product-quality risks
One-hour stability after reconstitution for the lyophilized product; ready-to-use (RTU) solution also available.
Must not be mixed with other drugs in the IV line.
Interactions and special populations
Increased bleeding with anticoagulants (heparin, warfarin, GPIs), antiplatelet agents. No CYP metabolism. Renal clearance: reduce dose when CrCl <30 mL/min. Elderly: increased bleeding risk due to age-related renal decline. Geriatric and renally impaired patients should be monitored closely.
Regulatory, compounding, and sport notes
WADA status: not prohibited. No US federal CSA scheduling was identified as of 2026-08-06; state law and other jurisdictions were not assessed. Generic and ready-to-use product availability is product- and jurisdiction-specific.
Evidence gaps
Comparative effectiveness vs unfractionated heparin alone (without GPI) in contemporary PCI practice with potent P2Y12 inhibitors.
Optimal use in ACS patients not undergoing PCI (labeled limitation).
Long-term safety beyond procedural use.
Search notes
Databases and registries: FDA label (accessdata.fda.gov), DailyMed, ClinicalTrials.gov, PubMed
Search terms: bivalirudin, Angiomax, Angiox, REPLACE-2, BAT, PCI, HIT
Last searched: 2026-08-06
Inclusion emphasis: FDA/EMA labels, phase 3 RCTs
Sources
FDA prescribing information: ANGIOMAX (bivalirudin) for injection. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/020873s036lbl.pdf (accessed 2026-08-06).
Lincoff AM, et al. Bivalirudin and provisional glycoprotein IIb/IIIa blockade compared with heparin and planned glycoprotein IIb/IIIa blockade during percutaneous coronary intervention: REPLACE-2 randomized trial. JAMA. 2003;289(7):853-63. DOI: 10.1001/jama.289.7.853.
Bittl JA, et al. Bivalirudin versus heparin during coronary angioplasty for unstable or post-infarction angina: final report reanalysis of the Bivalirudin Angioplasty Study. Am Heart J. 2001;142(6):952-8. DOI: 10.1067/mhj.2001.119378.
DailyMed: Bivalirudin injection. Available at: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c20969cb-72d4-469b-9bd8-332250d896c3 (accessed 2026-08-06).