A direct acting synthetic antithrombotic agent utilized as an alternative to unfractionated heparin for patients with acute coronary artery syndromes who are undergoing percutaneous intervention.
As a monotherapy compared to unfractionated heparin plus glycoprotein IIb/IIIa inhibitors there was a significant reduction in major and minor bleeding episodes with similar rates of ischemic events and death among patients with stable and unstable angina when undergoing percutaneous coronary artery interventions.
Compared with bivalirudin, heparin reduces the incidence of major adverse ischaemic events in the setting of PCI, with no increase in bleeding.
Approved for patients with or at risk for heparin induced thrombocytopenia and heparin induced thrombosis syndrome and undergoing percutaneous coronary intervention.
Harmonizin Outcomes with Revascularization and Stents in Acute Myocardial Infarction Study (HORIZONS AMI) supports use in ST-elevation myocardial infarction (STEMI) patients undergoind primay PCI demonstrating efficacy and reductions in major bleeding versus heparin plus GPIIb/IIIa inhibitors.
Reduces thrombin generation and both thrombin dependent and collagen dependent platelet activation.
HORIZONS-AMI trial bivalirudin during primary PCI decreases bleeding and thrombocytopenia while suppressing ischemic complications compared with unfractionated heparin plus glycoprotein IIb/IIIa inhibitors reducing all cause and cardiac mortality.
Bivalirudin
A specific and reversible direct thrombin inhibitor.
Trade name Angiomax
Intravenous injection therapy with a half-life of approximately 25 minutes in patients with normal renal function.
Cleared from plasma by a combination of renal mechanisms and proteolytic cleavage.
A synthetic congener of the naturally occurring drug hirudin, found in the saliva of the leech Hirudo medicinalis.
A synthetic peptide that is potent, highly specific, and a reversible inhibitor of thrombin.
It inhibits both circulating and clot-bound thrombin.
Directly inhibits thrombin by specifically binding both to the catalytic site and to the anion-binding exosite of circulating and clot-bound thrombin.
Binding of bivalirudin to thrombin is reversible as thrombin slowly cleaves the bivalirudin-Arg3-Pro4 bond, resulting in recovery of thrombin active site functions.
Inhibits thrombin-mediated platelet activation and aggregation.
Has a rapid onset of action and a short half-life.
Has a predictable anti thrombotic response as it does not bind to plasma proteins, except for thrombin.
Not associated with heparin induced thrombocytopenia.
Does not require a binding cofactor such as antithrombin and does not activate platelets.
Efficacious in patients with stable angina, unstable angina, non-ST segment elevation myocardial infarction (NSTEMI), and ST-segment elevation myocardial infarction (STEMI) undergoing PCI.
Indicated for use as an anticoagulant in patients with unstable angina undergoing percutaneous transluminal coronary angioplasty.
Bivalirudin with use of glycoprotein IIb/IIIa inhibitor (GPI) is indicated for use as an anticoagulant in patients undergoing percutaneous coronary intervention (PCI).
Indicated for patients with, or at risk of HIT syndrome undergoing PCI.
Intended for use with aspirin and clopidogrel
Following an IV bolus of bivalirudin of 1 mg/kg and a 4-hour 2.5 mg/kg/h IV infusion a mean steady state concentration is achieved.
It is cleared from plasma by a combination of renal mechanisms and proteolytic cleavage.
Half-life with normal renal function (≥ 90 mL/min) = 25 minutes, with mild renal dysfunction (60–89 mL/min) = 22 minutes, with moderate renal dysfunction (30-59 mL/min) = 34 minutes, and with severe renal dysfunction (≤ 29 mL/min) = 57 minutes.
In dialysis patients its half-life is 3.5 hours.
Is hemodialyzable and approximately 25% is cleared by hemodialysis.
Coagulation times return to baseline approximately 1 hour following cessation of bivalirudin administration.
Dosing: PCI Bolus: 0.75 mg/kg, PCI Infusion: 1.75 mg/kg/h for unstable angina/NSTEMI
Infusion: 0.25 mg/kg/h for up to 72 hours for medical management and if patient proceeds to PCI, an additional bolus of 0.5 mg/kg of bivalirudin should be administered before the procedure and the infusion increased to 1.75 mg/kg/h for the duration of the procedure.
For patients proceeding to CABG surgery off-pump: The IV infusion should be continued until the time of surgery, and just prior to surgery, a 0.5 mg/kg bolus dose should be administered followed by a 1.75 mg/kg/h infusion for the duration of the surgery.
For patients proceeding to CABG surgery on-pump: The IV infusion of should be continued until 1 hour prior to surgery after which the infusion should be discontinued.
Continuation of the bivalirudin infusion following PCI for up to 4 hours post-procedure is optional, but after 4 hours, an additional IV infusion of bivalirudin may be initiated at a rate of 0.2 or 0.25 mg/kg/h for up to 20 hours, if needed.
Should be administered with optimal antiplatelet therapy of aspirin plus clopidogrel.
Infusion dose reduction should be considered in patients with moderate or severe renal impairment.
Contraindicated in patients with active major bleeding, in patients with an increased risk of bleeding due to hemostasis disorders and/or irreversible coagulation disorders, severe uncontrolled hypertension, subacute bacterial endocarditis, and severe renal impairment [GFR<30 ml/min] and in dialysis-dependent patients.
Bivalirudin treated patients have significantly lower rates of bleeding than patients treated with heparin plus a GP IIb/IIIa inhibitor.
Bivalirudin with or without provisional GPIIb/IIIa demonstrated similar angiographic and procedural outcomes and improved clinical outcomes when compared with heparin plus GPIIb/IIIa.
Patients receiving monotherapy had similar rates of overall stent thrombosis at 30 days versus UFH plus a GP IIb/IIIa inhibitor (2.5% vs. 1.9%).
Cardiac deaths reduced in patients treated with bivalirudin monotherapy versus UFH plus a GP IIb/IIIa inhibitor was maintained at 1 year in the HORIZONS AMI trial (2.1% vs. 3.8%)
Looking at the 2-year follow-up, a reduction in the incidence of adverse clinical events (22.3% vs. 24.8%) and major bleeding (6.4% vs. 9.6%) was maintained in the bivalirudin monotherapy group versus UFH plus a GP IIb/IIIa inhibitor group.
At the 2-year period there was no difference in the rate of major adverse cardiovascular events.
A significant reduction in the rate of cardiac mortality in patients treated with bivalirudin monotherapy versus UFH plus a GP IIb/IIIa inhibitor was maintained at 2 year in the HORIZONS AMI trial (2.5% vs. 4.2%).
At 2-year follow-up, treatment with bivalirudin monotherapy results in a 25% reduction in all-cause mortality, representing 15 lives saved per 1000 patients treated.
The incidence of stent thrombosis at 2 years is similar between the 2 treatment groups, 4.6% in the bivalirudin group vs. 4.3% in the UFH plus GP IIb/IIIa inhibitor group.
In the ACUITY multicenter, prospective, open-label, 3-arm trial to establish the optimal antithrombotic treatment regimens in patients with unstable angina/NSTEMI undergoing early invasive management: Bivalirudin monotherapy provided superior clinical outcomes compared to any heparin regimen with GP IIb/IIIa inhibitor at 30 days.
REPLACE-2 was a multicenter, double-blind, randomized clinical trial in patients with low to moderate risk for ischemic complications undergoing PCI: The incidence of net adverse clinical events and major adverse cardiovascular events are reduced by bivalirudin monotherapy versus unfractionated heparin (UFH) plus a GP IIb/IIIa inhibitor with significant reduction in rates of major bleeding at 30 days.
In the above studies the differences in mortality favoring bivalirudin at 30 days and 6 months was maintained at 12 months and demonstrated a 24% risk reduction in death compared to heparin plus GP IIb/IIIa inhibition.