Bivalirudin

Angiomax, Angiox (EU brand), Hirulog-8, BG8967

Cardiovascular & circulation

Awaiting medical reviewEN ES DE FR PT ZH+ Follow for updates

Note on this profile. Bivalirudin is an approved hospital-only anticoagulant given intravenously during heart procedures. It is not a research-only compound and has no self-directed or community use. This page explains the published science so it can be read alongside other peptides on the site.

1What it is

Bivalirudin is a short, fully synthetic peptide built in the early 1990s to copy the two parts of hirudin that matter: a short segment that plugs thrombin's active site, joined by a flexible glycine linker to a 12-amino-acid tail that binds thrombin's "exosite 1", the docking point for fibrinogen. Hirudin itself (and its recombinant versions, lepirudin and desirudin) binds thrombin almost irreversibly; bivalirudin was designed so that thrombin can cut the peptide after binding, restoring its own activity within minutes. That gives a predictable, short anticoagulant effect that suits the cath lab.

It was developed by Biogen, then The Medicines Company, and approved by the FDA in December 2000 for use during coronary angioplasty. Generic versions have been available since 2015. It is a hospital drug: there is no community or self-directed use, and none would make sense given its and route.

2How it's thought to work

Thrombin is the final enzyme in the clotting cascade; it converts fibrinogen to fibrin and activates platelets. Bivalirudin binds the thrombin catalytic site (via its N-terminal D-Phe-Pro-Arg-Pro segment) and exosite 1 at the same time, inhibiting both free and clot-bound thrombin — unlike heparin, which needs antithrombin and cannot reach thrombin inside a clot.

Thrombin slowly cleaves the Arg3–Pro4 bond of the bound peptide, which releases the active site. This is why the effect wears off within about an hour of stopping the infusion.

It does not bind platelet factor 4 or plasma proteins, so it does not cause heparin-induced thrombocytopenia (HIT) and its dose–response is more predictable than heparin's.

Clearance is about 80% by proteolysis and 20% by the kidneys, so doses are adjusted for kidney function.

A twenty-amino-acid peptide that occupies both the active site and the substrate groove of thrombin, so fibrinogen is never cut and the clot is not built. Thrombin slowly cleaves it free, which makes the effect short and self-limiting.Schematic — not to scale

3What the research shows

Anticoagulation during PCI vs heparin (± GP IIb/IIIa inhibitor)

REPLACE-2 (n≈6,010) found bivalirudin with provisional glycoprotein IIb/IIIa inhibitor non-inferior to heparin plus planned GP IIb/IIIa inhibitor for ischaemic events, with less major bleeding (2.4% vs 4.1%) (Lincoff 2003, JAMA). ACUITY (n≈13,819, acute coronary syndromes) reported similar ischaemic outcomes and less bleeding with bivalirudin alone (Stone 2006, NEJM). [2][3]

Graded A (mixed)

Heart attack (STEMI) undergoing primary PCI

HORIZONS-AMI (n≈3,602) reported lower 30-day major bleeding and lower cardiac mortality with bivalirudin than heparin plus GP IIb/IIIa inhibitor, but a higher rate of acute stent thrombosis in the first 24 h (Stone 2008, NEJM). HEAT-PPCI (n≈1,829, single centre, UK) then found heparin alone produced fewer ischaemic events than bivalirudin with no bleeding advantage (Shahzad 2014, Lancet). MATRIX (n≈7,213) and VALIDATE-SWEDEHEART (n≈6,006) found no clear difference in death, MI or major bleeding between the two in the era of radial access and potent oral antiplatelets (Valgimigli 2015, NEJM; Erlinge 2017, NEJM). The most recent large trial, BRIGHT-4 (n=6,016, China, mostly radial access), used a prolonged full-dose infusion after PCI and reported fewer deaths or major bleeds at 30 days (3.1% vs 4.4%) and less stent thrombosis (0.4% vs 1.1%) than heparin alone (Li 2022, Lancet; confirmed via ACC trial summary). The weight of evidence is that bivalirudin reduces bleeding; whether it changes death or MI depends on how it is given and what it is compared with. [4][5][6][7][8]

Heparin-induced thrombocytopenia (HIT) in PCI

Small open-label studies and registries support its use when heparin cannot be given; the US label includes PCI in patients with HIT (Mahaffey 2003, J Invasive Cardiol).

Cardiac surgery and ECMO

Uncontrolled and small randomised studies (e.g. CHOOSE-ON, EVOLUTION) support use as a heparin alternative in cardiopulmonary bypass and extracorporeal support; growing observational use in paediatric ECMO. Off-label.

Community / self-directed use

None documented; not meaningful for an IV-only anticoagulant.

4Reported side effects and interactions

Literature-reported

Bleeding is the principal risk, as with any anticoagulant, though consistently lower than heparin plus GP IIb/IIIa inhibitor in trials. Other reported events: back pain, hypotension, nausea, headache, injection-site pain. Acute stent thrombosis in the first hours after primary PCI was seen in HORIZONS-AMI and EUROMAX and is the reason for prolonged post-procedure infusion in later trials. Rare: antibody formation (low titre, no clinical consequence found), hypersensitivity.

Community-reported

none; no community use.

Theoretical. no antidote exists; management of over-anticoagulation is to stop the infusion (effect wanes in ~1 h) and, in extremis, haemodialysis or haemofiltration removes it.

Interactions. additive bleeding risk with other anticoagulants, antiplatelets and thrombolytics (pharmacodynamic, not metabolic). No cytochrome P450 involvement.

Markers researchers commonly monitor

These follow the label and cath-lab practice:

Marker	Why it's watched
Activated clotting time (ACT)	the point-of-care measure used during PCI; bivalirudin raises ACT predictably within 5 minutes of the bolus.
aPTT	used in cardiac surgery and ECMO protocols where ACT is less reliable; target ranges are institutional.
Haemoglobin / haematocrit	bleeding is the key adverse event; checked after the procedure.
Platelet count	to distinguish bivalirudin use from HIT; bivalirudin itself does not lower platelets.
Creatinine / eGFR	the infusion rate is reduced in renal impairment because ~20% of clearance is renal.
Signs of stent thrombosis (ECG, chest pain) in the first 24 h	the specific risk window identified in STEMI trials.

Free for everyone. Safety information is never behind a paywall.

5Reconstitution and handling

Hospital pharmacy or cath-lab preparation only: a 250 mg vial is with 5 mL sterile water (50 mg/mL) and diluted in 50 mL of 5% dextrose or 0.9% saline to 5 mg/mL for bolus and infusion. Do not mix in the same line with several listed drugs (e.g. alteplase, amiodarone, diazepam, prochlorperazine). Not supplied for or appropriate to home use; the calculator is not applicable.

6Commonly studied alongside

Aspirin and P2Y12 inhibitors (clopidogrel, ticagrelor, prasugrel) as background therapy; glycoprotein IIb/IIIa inhibitors such as eptifibatide (profile 132), abciximab and tirofiban, used either alongside or as the comparator arm; unfractionated heparin as the standard comparator; cangrelor in recent regimens.

Informational cross-links. Not stack recommendations.

7Regulatory status by region

Region	Status (checked —)
United States	FDA-approved (Angiomax, December 2000) for PCI including patients with HIT/HITTS; multiple generics since 2015
European Union	EMA-authorised (Angiox, 2004) for PCI and for adults with acute coronary syndromes planned for urgent/early intervention; generics authorised
United Kingdom	MHRA-licensed (Angiox and generics); hospital only
Australia	TGA-registered (Angiomax and generics) †
South Africa	Registered with SAHPRA †
Sport	Not prohibited by WADA

8Open questions

Does a prolonged full-dose infusion after PCI (the BRIGHT-4 approach) reproduce its benefit outside China and with routine ticagrelor/prasugrel?
Optimal dosing and monitoring in cardiopulmonary bypass and ECMO, where use is off-label and growing.
Whether reduced bleeding translates to better survival in contemporary radial-access practice.

9References

1Maraganore JM et al. (1990). Design and characterization of hirulogs: a novel class of bivalent peptide inhibitors of thrombin. Biochemistry. PubMed · DOI
2Lincoff AM et al. (2003). 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. PubMed · DOI
3Stone GW et al. (2006). Bivalirudin for patients with acute coronary syndromes (ACUITY). NEJM. PubMed · DOI
4Stone GW et al. (2008). Bivalirudin during primary PCI in acute myocardial infarction (HORIZONS-AMI). NEJM. PubMed
5Shahzad A et al. (2014). Unfractionated heparin versus bivalirudin in primary percutaneous coronary intervention (HEAT-PPCI). Lancet. PubMed
6Valgimigli M et al. (2015). Bivalirudin or unfractionated heparin in acute coronary syndromes (MATRIX). NEJM. PubMed · DOI
7Erlinge D et al. (2017). Bivalirudin versus heparin monotherapy in myocardial infarction (VALIDATE-SWEDEHEART). NEJM. PubMed · DOI
8Li Y et al. (2022). Bivalirudin plus a high-dose infusion versus heparin monotherapy in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention (BRIGHT-4). Lancet. DOI
9FDA. Angiomax (bivalirudin) prescribing information (current label). PubMed

References are being resolved to PubMed/DOI identifiers; links search PubMed for the citation until then.

† Being confirmed by our reviewers against current sources.

10Community

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Self-reported side effects Phase 2

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11Page history

30 Oct 2026Profile published — awaiting medical review

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