What it is
Bivalirudin is a synthetic peptide of 20 amino acids that blocks thrombin, the enzyme at the centre of blood clotting. The label calls it "a specific and reversible direct thrombin inhibitor" with a molecular weight of 2,180 daltons. Written in one-letter code, the chain reads:
f P R P G G G G N G D F E E I P E E Y L
The lower-case f is D-phenylalanine, the mirror-image form of the amino acid; the other nineteen are ordinary L-amino acids (our transcription of the label's chemical name). Bivalirudin was not found in nature. It was designed at Biogen and first described in 1990 as hirulog-1: an active-site blocking sequence, D-Phe-Pro-Arg-Pro, then a linker of glycines, then a recognition sequence like the end of hirudin, the 65-amino-acid anticoagulant protein of the medicinal leech (Maraganore et al., Biochemistry 1990, PMID 2223763; UniProt P01050). The paper calls the class "bivalent peptide inhibitors of thrombin" — the root of the name.
How it works
Thrombin turns fibrinogen into fibrin, the mesh of a clot, and activates platelets and other clotting factors. The label states that bivalirudin binds both the catalytic site and the anion-binding exosite of thrombin — the business end and a second docking site — on circulating and clot-bound thrombin alike. In the 1990 design paper, the active-site piece alone (D-Phe-Pro-Arg-Pro-Gly) inhibited thrombin weakly (Ki above 2 micromolar) and hirudin's tail peptide alone blocked clotting but not the active site; joined by the glycines, hirulog-1 inhibited thrombin with a Ki of 2.3 nanomolar — the two halves working together.
The block does not last. Thrombin "slowly cleaves the bivalirudin-Arg3-Pro4 bond", restoring its own active site (label). That self-limiting design is why bivalirudin is called reversible, and it sits behind the short half-life below.
How fast it clears
| Kidney function (label) | Half-life |
|---|---|
| Normal | 25 minutes |
| Moderate impairment | 34 minutes |
| Severe impairment | 57 minutes |
| On dialysis | 3.5 hours |
The label adds that clotting times return to baseline about one hour after the infusion stops, that it does not bind plasma proteins other than thrombin, and that about 25% is removed by haemodialysis. Infusion rates are reduced in severe kidney impairment and dialysis, and are set by the hospital team.
What the trials showed
- BAT trials (label section 14): 4,312 people with unstable angina undergoing angioplasty, bivalirudin vs heparin. The trials "did not demonstrate that bivalirudin was statistically superior to heparin" on death, heart attack, abrupt vessel closure or urgent revascularisation — 7.9% vs 9.3% on the composite — and "the occurrence of these events was similar in both treatment groups." Major bleeding occurred in 79 of 2,161 bivalirudin patients (3.7%).
- AT-BAT (label): a single-arm, open-label study of 51 people with heparin-induced thrombocytopenia (HIT) or HIT with thrombosis undergoing PCI; most reached an adequate clotting time and no major bleeding was reported. It had no comparison group.
- HORIZONS-AMI (Stone et al., NEJM 2008, PMID 18499566): 3,602 people having primary PCI for an ST-elevation heart attack, bivalirudin alone vs heparin plus a glycoprotein IIb/IIIa inhibitor. At 30 days: major bleeding 4.9% vs 8.3%, net adverse clinical events 9.2% vs 12.1% — and more acute stent thrombosis in the first 24 hours with bivalirudin, with no significant difference by 30 days.
What the label warns
- Bleeding — the most common adverse reaction; an unexplained fall in blood pressure or haematocrit "should lead to serious consideration of a hemorrhagic event."
- Acute stent thrombosis in STEMI: within 4 hours in 1.2% (36/2,889) of bivalirudin-treated vs 0.2% (6/2,911) of heparin-treated patients, with one death in each group; the label calls for at least 24 hours' monitoring in a facility able to manage ischaemic complications.
- Brachytherapy: thrombus formation, including fatal outcomes, during gamma brachytherapy.
- Antibodies: of 494 people tested in trials, 2 developed antibodies to bivalirudin, neither with an allergic reaction (label section 6.2).
Where it stands
- Approved in the US since 2000-12-15 (Angiomax, NDA 020873); a ready-to-use form, Angiomax RTU, followed in 2019; ten applications in Drugs@FDA, eight of them generics (openFDA, 2026-10-26).
- Label used for this entry: bivalirudin for injection, effective 2025-09-10.
- Research record: PubMed indexes 2,210 records for "bivalirudin", 278 tagged as randomised trials; ClinicalTrials.gov lists 92 studies with it as an intervention (2026-10-26).
Related reading
Another approved peptide used in the cath lab is eptifibatide, a platelet blocker built on a snake-venom design, which acts on platelets rather than thrombin. Why a 20-residue chain counts as a peptide and the 65-residue leech hirudin as a protein is set out in peptide vs protein.