Bivalirudin

Bivalirudin is a drug used to prevent the coagulation (clotting) of blood during surgery to open clogged arteries. Bivalirudin is less likely to cause major bleeding episodes compared heparin, a common drug used to prevent coagulation.

Uses/Indications

Bivalirudin is an anticoagulant used to reduce the risk of developing blood clots during surgery in the following adult patients:

• Those who have unstable angina (severe chest pain) and are undergoing surgery to unplug arteries in the heart (percutaneous transluminal coronary angioplasty or PCTA)

• Who are undergoing surgery to open blocked arteries in the heart (percutaneous coronary intervention or PCI)

• Who are undergoing PCI and who have developed, or at a risk of developing heparin-induced thrombocytopenia, or heparin-induced thrombocytopenia and Thrombosis Syndrome.

A micrograph of cells in blood magnified 1000X. The arrow indicates aggregation of platelets. In addition, several red blood cells and a polymorphonuclear leukocyte. The platelets are involved in the clotting process.

How Bivalirudin Is Taken

Before using, bivalirudin must be mixed with sterile water to make a solution of 250 mg bivalirudin per vial. Physicians inject the drug intravenously. Physicians typically start the infusion with 0.75 mg/kg and maintain the dose at 1.75mg/kg per hour throughout the surgery. Bivalirudin is sometimes infused up to 20 hours after the surgery. Often other drugs such as aspirin and a glycoprotein IIb/IIIa inhibitor are given in combination with bivalirudin.

How Bivalirudin Works

Thrombin is a substance in the blood that activates several proteins (factors) that are involved in the coagulation, or clotting, of blood. Bivalirudin prevents blood clotting by inhibiting thrombin. Bivalirudin is less likely to cause major bleeding complications than are some other anticoagulants because it is rapidly inactivated and does not stay bound to thrombin.

How the Body Affects Bivalirudin

Because bivalirudin is quickly degraded, about half the concentration of bivalirudin in the blood is reduced in 25 minutes. The bivalirudin that is not degraded in the circulation is metabolized (broken down) in the kidney.

In Special Populations

Elimination of bivalirudin from the body is reduced approximately 70% in patients with severe kidney damage and is reduced about 45% in patients with moderate kidney damage.^[1] The risk of bleeding increases in patients with severe kidney damage because of the reduction in elimination. Bivalirudin is also eliminated about 80% more slowly in patients undergoing dialysis.^[2]

Side Effects

As with many anticoagulants, severe bleeding is the primary side effect of treatment with bivalirudin. In the REPLACE-2 trial, 2.4% of patients treated with bivalirudin had severe bleeding episodes.^[3] Major bleeding episodes are more likely in elderly rather than younger adult patients, in patients with severe kidney damage, or in patients undergoing dialysis. Some fatalities have occurred due to excessive bleeding. Fatalities have also resulted from serious anaphylactic (allergic) reactions. This anaphylaxis can occur in the skin or throughout the body.

Side effects most often associated with bivalirudin are the following:

• Back pain
• Very low or very high blood pressure
• Anxiety
• Nausea
• Injection site pain
• Insomnia
• Pelvic pain
• Headache
• Vomiting
• Slow heart rate
• Abdominal pain
• Fever
• Upset stomach

Risks and Precautions

Bivalirudin should not be used in patients who have a high risk of developing uncontrolled bleeding. Patients are at a high risk of developing bleeding complications if they have the following:

• Major bleeding
• A medical condition that increases the risk of bleeding
• A tendency to bleed easily

Bleeding risk can also be increased by the use of other drugs such as blood thinners, heparin, and thrombolytics (e.g., urokinase).

Dosage reductions are recommended for patients with moderate or severe renal impairment, or in patients undergoing dialysis.

Bivalirudin has not been studied in pregnancy. Women should consult a healthcare provider if an unplanned pregnancy occurs, or if pregnant. Nursing infants should be avoided during treatment with bivalirudin.

Drug Interactions

Studies have shown that several other drugs that reduce the coagulation of blood are safe when administered with bivalirudin. Other drugs that are commonly used in PCI and have been shown safe include aspirin, clopidogrel (Plavix),ticlopidine (Ticlid), abciximab (ReoPro), eptifibatide (Integrilin) or tirofiban (Aggrastat). However, the combined use of anticoagulant drugs may increase the risk of bleeding.

Clinical Trials

The outcome of surgery is very similar in patients receiving bivalirudin or heparin, with one exception. Bivalirudin has a significant advantage over heparin because it is less likely to cause excessive bleeding.

The REPLACE-2 trial compared surgery outcome after treatment with either bivalirudin or heparin.^[4] The incidence of death, heart attack, revascularization, or major bleeding was 9.2% and 10% in patients receiving bivalirudin and heparin, respectively. However, 2.4% of patients treated with bivalirudin had a major bleeding episode compared to 4.1% of patients treated with heparin. A follow-up of the REPLACE-2 study showed that 1.8% and 2.6% of patients treated with bivalirudin and heparin, respectively, had died after one year.^[5]

The Hirulog Angioplasty Study showed that bleeding episodes are reduced during PCTA surgery in patients treated with bivalirudin compared to patients treated with heparin.^[6] In the trial, 2.4% of bivalirudin-treated and 12% of heparin-treated patients had major bleeding episodes.

Interesting Fact

Bivalirudin is a synthetic form of a compound derived from the saliva of the leech Hirudo medicinalis. Leeches feed by sucking blood from other animals, and they use a natural blood thinner to keep the blood from clotting. This blood thinner led to the development of bivalirudin.

References

1. ↑ Robson R. The use of bivalirudin in patients with renal impairment. Abstract. J Invasive Cardiol 2000;12:33F-6.
2. ↑ Robson R. The use of bivalirudin in patients with renal impairment. Abstract. J Invasive Cardiol 2000;12:33F-6.
3. ↑ Lincoff AM, Bittl JA, Harrington RA, 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;289:853-63.
4. ↑ Lincoff AM, Bittl JA, Harrington RA, 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;289:853-63.
5. ↑ Lincoff AM, Kleiman NS, Kereiakes DJ, et al. Long-term efficacy of bivalirudin and provisional glycoprotein IIb/IIIa blockade vs heparin and planned glycoprotein IIb/IIIa blockade during percutaneous coronary revascularization: REPLACE-2 randomized trial. JAMA 2004;292:696-703.
6. ↑ Bittl JA, Feit F. A randomized comparison of bivalirudin and heparin in patients undergoing coronary angioplasty for postinfarction angina. Hirulog Angioplasty Study Investigators. Abstract. Am J Cardiol 1998;82:43P-49P.

External Links

• University of Maryland Medical Center: Coronary Artery Disease
• Food and Drug Administration: ‘Angiomax: Bivalirudin Product Information
• Food and Drug Administration: Bivalirudin, Marketed as Angiomax, Information Sheet
• Drugs.com Complete Bivalirudin Information
• Druglib: Angiomax (Bivalirudin) - Drug Information, Research, Clinical Trials, News