Peptide education
Bivalirudin
Angiomax · Angiomax RTU
Bivalirudin is an intravenous anticoagulant used during a coronary procedure called percutaneous coronary intervention, or PCI. It blocks thrombin, an enzyme that helps blood clot. The US Angiomax RTU label includes patients who have heparin-induced thrombocytopenia, a serious reaction to heparin.
In HORIZONS-AMI, major bleeding unrelated to coronary bypass surgery within 30 days occurred in 4.9% of patients assigned to bivalirudin with provisional glycoprotein IIb/IIIa inhibitor use and 8.3% assigned to heparin with planned use of that type of platelet inhibitor. Both groups also received oral antiplatelet treatment. Acute stent thrombosis within 24 hours was more frequent in the bivalirudin group.
Overview
Quick answer
Bivalirudin is given by intravenous bolus and infusion during PCI. Kidney function affects its clearance, and trial results depend on the other drugs given and how long the infusion continues.
What is bivalirudin used for?
The US label describes anticoagulation during PCI, including for patients with heparin-induced thrombocytopenia or heparin-induced thrombocytopenia with thrombosis. PCI uses a catheter to treat a coronary artery and may include a stent.
How is it given?
Angiomax RTU is given intravenously as a weight-based bolus followed by an infusion for the procedure. Clinicians check activated clotting time and adjust the infusion for specified levels of kidney impairment.
Is it always safer than heparin?
That depends on the comparison. HORIZONS-AMI compared provisional versus planned use of glycoprotein IIb/IIIa inhibitors alongside different anticoagulants. BRIGHT-4 reserved those inhibitors for complications in both groups. Both trials also used oral antiplatelet medicines. Neither proves every bivalirudin strategy is safer than every heparin strategy.
Does its effect disappear in 25 minutes?
No. The label reports a 25-minute half-life in PCI patients with normal kidney function, while clotting times return to baseline at approximately one hour after the infusion stops. Reduced kidney function can prolong exposure.
What is the main risk?
Bleeding can be serious. The label also identifies active major bleeding and hypersensitivity as contraindications and warns of thrombosis associated with coronary gamma brachytherapy.
Evidence
Evidence snapshot
Angiomax RTU is labeled as an anticoagulant for people undergoing PCI, including those with heparin-induced thrombocytopenia or its associated thrombosis syndrome.
Of 3,602 patients assigned to a primary PCI strategy, 3,345 underwent primary PCI. The bivalirudin strategy had less major bleeding unrelated to bypass surgery at 30 days, but more acute stent thrombosis within 24 hours.
Among 6,016 randomized patients, the 30-day composite of death or major bleeding defined as BARC type 3 to 5 was 3.06% with bivalirudin plus a post-PCI infusion and 4.39% with heparin as the anticoagulant. Both groups also received oral antiplatelet therapy. Radial artery access was used in most procedures.
The Angiomax RTU label lowers the infusion rate when creatinine clearance is below 30 mL/min and provides a separate rate for patients receiving hemodialysis.
Claims
Common claims vs evidence
| Claim | Human evidence | Mechanistic evidence | Verdict |
|---|---|---|---|
| Bivalirudin can be used during PCI in patients with heparin-induced thrombocytopenia. | The cited US label expressly includes PCI patients with heparin-induced thrombocytopenia and those with the related thrombosis syndrome. | Bivalirudin directly inhibits thrombin rather than acting through heparin. | The US label includes patients with heparin-induced thrombocytopenia undergoing PCI. |
| Bivalirudin has been shown to reduce bleeding in every PCI comparison. | HORIZONS-AMI compared provisional with planned glycoprotein IIb/IIIa inhibition alongside different anticoagulants. BRIGHT-4 tested a post-PCI bivalirudin infusion against heparin, reserving those inhibitors for complications. Both trials also used oral antiplatelet medicines. | The specific combination and duration of medicines are part of the comparison. | Too broad. Each result belongs to the tested treatment strategy and population. |
| Short action means bleeding or clotting risks are negligible. | The label warns of bleeding and describes slower drug clearance with kidney impairment. HORIZONS-AMI reported more acute stent thrombosis in its bivalirudin arm. | Bivalirudin inhibits thrombin reversibly, but the drug's half-life is not the same measurement as the time until coagulation tests return to baseline. | Not supported. A short half-life does not remove the need for monitoring or resolve the separate risk of a clot forming around a stent. |
Bottom line
Main takeaway
Bivalirudin is a prescription blood thinner given by a medical team during a coronary procedure. It can cause serious bleeding.
Read the comparator, other medicines, kidney function, procedure, and infusion duration before applying a trial's bleeding or clotting result to another setting.
HORIZONS-AMI used planned glycoprotein IIb/IIIa inhibition in the heparin group. BRIGHT-4 compared heparin with a bivalirudin infusion continued after PCI. Both trials also used oral antiplatelet medicines.
Identity
What it is
Bivalirudin is a synthetic 20-amino-acid peptide that directly and reversibly inhibits thrombin. Angiomax RTU is a ready-to-use intravenous product.
In PCI, the medical team uses a catheter to treat a narrowed coronary artery. Anticoagulation is part of the procedure, and the label includes people with heparin-induced thrombocytopenia.
Use context
Routes, doses, and cycle patterns
The Angiomax RTU label describes intravenous dosing during PCI, with infusion adjustments for severe kidney impairment and hemodialysis. HORIZONS-AMI generally stopped treatment after angiography or PCI, while BRIGHT-4 continued the infusion for 2 to 4 hours after PCI.
Human studies and product labels
Angiomax RTU label, PCI
- Purpose
- Anticoagulation during PCI
- Context
- US prescribing information
- Route
- Intravenous
- Amount
- 0.75 mg/kg bolus followed immediately by 1.75 mg/kg/hour infusion
- Frequency
- Continuous infusion during the procedure
- Duration
- Procedure duration; see label for possible extension after STEMI PCI
The label calls for activated clotting time assessment five minutes after the bolus to determine whether an additional 0.3 mg/kg bolus is needed. It says to consider continuing 1.75 mg/kg/hour for up to four hours after PCI for STEMI.
Angiomax RTU label, kidney impairment
- Purpose
- Infusion adjustment during PCI
- Context
- US prescribing information
- Route
- Intravenous
- Amount
- 1 mg/kg/hour if creatinine clearance is below 30 mL/min; 0.25 mg/kg/hour on hemodialysis
- Frequency
- Continuous infusion
- Duration
- As directed in the full product label
The label does not reduce the initial bolus for kidney impairment. These rates refer to the maintenance infusion and require clinical monitoring.
HORIZONS-AMI
- Purpose
- Primary PCI strategy for ST-elevation myocardial infarction
- Context
- Open-label randomized trial
- Route
- Intravenous
- Amount
- 0.75 mg/kg bolus followed by 1.75 mg/kg/hour infusion
- Frequency
- Infusion during angiography or PCI
- Duration
- Protocol stopped treatment after angiography or PCI, with low-dose continuation allowed when clinically indicated
The bivalirudin group had provisional glycoprotein IIb/IIIa inhibitor use. The comparator received heparin with planned glycoprotein IIb/IIIa inhibition.
BRIGHT-4
- Purpose
- Primary PCI for ST-elevation myocardial infarction
- Context
- Open-label randomized trial at centers in China
- Route
- Intravenous
- Amount
- Bivalirudin with a high-dose post-PCI infusion
- Frequency
- Post-procedure infusion continued for 2 to 4 hours
- Duration
- Procedure and post-PCI infusion
Heparin was the comparator anticoagulant. Both groups received oral antiplatelet treatment, with glycoprotein IIb/IIIa inhibitors reserved for procedural thrombotic complications.
What varies
- The indication, procedure, and concomitant antithrombotic medicines define the comparison.
- Kidney function affects clearance and the labeled infusion rate.
- A half-life, the time to laboratory recovery, and infusion duration are different measurements.
Research
Research evidence
Randomized trials support procedural use in defined coronary populations. HORIZONS-AMI and BRIGHT-4 tested different treatment strategies and reported different composite outcomes. Their findings do not establish a result for an untested drug combination or a different clinical setting.
| Study / evidence area | Population | Design | Product context | Main outcome | Limitations | Weight |
|---|---|---|---|---|---|---|
| HORIZONS-AMI | 3,602 patients with ST-elevation myocardial infarction assigned to a primary PCI strategy; 3,345 underwent primary PCI | Open-label randomized comparison | Bivalirudin with provisional glycoprotein IIb/IIIa inhibition versus heparin with planned inhibition; both groups received oral antiplatelet treatment | At 30 days, major bleeding unrelated to coronary bypass surgery was 4.9% versus 8.3%, and net adverse clinical events were 9.2% versus 12.1%, respectively. Acute stent thrombosis within 24 hours was more frequent with bivalirudin. | The comparator included a planned glycoprotein IIb/IIIa inhibitor, and the finding for acute stent thrombosis qualifies the overall benefit and risk comparison. | Strong for the strategies tested |
| BRIGHT-4 | 6,016 patients with ST-elevation myocardial infarction undergoing primary PCI | Open-label randomized comparison at centers in China | Bivalirudin plus 2 to 4 hours of post-PCI infusion versus heparin as the anticoagulant; both groups received oral antiplatelet treatment | Death or major bleeding defined as BARC type 3 to 5 at 30 days occurred in 3.06% versus 4.39%, respectively. Stent thrombosis at 30 days occurred in 0.37% versus 1.10%. | Most procedures used radial access; the result concerns the specific infusion and comparator tested, not every PCI setting or dosing strategy. | Strong for the strategies tested |
Use context
Reported use context
HORIZONS-AMI studied bivalirudin during angiography or PCI. BRIGHT-4 continued the infusion for 2 to 4 hours after PCI.
Study and label context
0.75 mg/kg bolus followed by 1.75 mg/kg/hour during angiography or PCI.
Bivalirudin with a high-dose infusion continued for 2 to 4 hours after PCI.
Cautions
Safety and unknowns
- Bivalirudin increases bleeding risk. The label contraindicates it in patients with significant active bleeding or hypersensitivity to the product or its components.
- Impaired kidney function reduces clearance; the label specifies lower infusion rates for severe impairment and hemodialysis, with anticoagulation monitoring.
- HORIZONS-AMI reported more acute stent thrombosis within 24 hours in the bivalirudin strategy. The label also warns of thrombus formation with coronary gamma brachytherapy.
- The label states that pediatric safety and effectiveness are not established and that there is no known antidote for bivalirudin overdose.
Product quality
Product identity and quality
Angiomax RTU is a sterile, ready-to-use intravenous solution with a specified concentration and storage instructions.
FDA does not approve compounded drugs or review their quality, safety, and effectiveness before marketing. Product identity and sterility cannot be inferred from a name alone.
Product and concentration
The label describes a particular ready-to-use intravenous product.
Clinical oversight
Kidney function, clotting tests, and bleeding risk affect the labeled procedure.
Non-approved products
A product sold under the same ingredient name is not automatically equivalent.
Mechanism
How it is proposed to work
Bivalirudin blocks thrombin directly. Thrombin helps form fibrin, the material that stabilizes a clot, and also activates platelets.
The drug binds both the active site and an exosite on circulating and clot-bound thrombin. Thrombin can cleave the drug, allowing active-site function to recover.
The label reports a 25-minute half-life in PCI patients with normal renal function and approximately one hour for coagulation times to return to baseline after stopping administration. Kidney impairment prolongs the half-life.
FAQ
Common questions
Is bivalirudin a substitute for every use of heparin?
No. The cited US label is for anticoagulation during PCI, including PCI in patients with heparin-induced thrombocytopenia. Other clinical uses require separate evidence and medical judgment.
Does the drug wear off completely in 25 minutes?
No. The label reports a 25-minute half-life in PCI patients with normal renal function and approximately one hour for coagulation times to return to baseline after stopping. Kidney impairment can prolong exposure.
Details
Technical details
Sources
References
- 1.
DailyMed. Angiomax RTU (bivalirudin) prescribing information
US indication, intravenous dosing, renal adjustment, pharmacology, and safety warnings.
- 2.
PubMed. Bivalirudin during primary PCI in acute myocardial infarction
doi:10.1056/NEJMoa0708191 PMID:18499566 NCT00433966
HORIZONS-AMI compared bivalirudin with heparin plus planned glycoprotein IIb/IIIa blockade.
- 3.
New England Journal of Medicine. Bivalirudin during primary PCI in acute myocardial infarction
doi:10.1056/NEJMoa0708191 PMID:18499566
Full trial report defines major bleeding unrelated to coronary bypass surgery and describes background antiplatelet treatment.
- 4.
doi:10.1016/j.jacc.2011.07.021 PMID:21996385
Trial analysis reports how many randomized patients underwent primary PCI.
- 5.
doi:10.1016/S0140-6736(22)01999-7 PMID:36351459 NCT03822975
BRIGHT-4 compared bivalirudin with a post-procedure infusion against heparin without routine glycoprotein IIb/IIIa blockade.
- 6.
doi:10.1186/s12916-024-03579-6
Prespecified trial analysis describes background oral antiplatelet therapy and bailout GPI use.
- 7.
FDA. Compounding and the FDA: Questions and Answers
FDA describes the approval and premarket review limits for compounded drugs.