Some of the views expressed in the following notes on newly approved products should be regarded as preliminary, as there may have been limited published data at the time of publication, and little experience in Australia of their safety or efficacy. However, the Editorial Executive Committee believes that comments made in good faith at an early stage may still be of value. Before new drugs are prescribed, the Committee believes it is important that more detailed information is obtained from the manufacturer's approved product information, a drug information centre or some other appropriate source.
vials containing 250 mg lyophilised powder for reconstitution
Approved indication: percutaneous coronary intervention
Australian Medicines Handbook section 7.1
Patients having procedures such as percutaneous transluminal coronary angioplasty need to be anticoagulated. While heparin can be used, some patients still develop ischaemia and there is a risk of major bleeding.
Bivalirudin is a direct inhibitor of thrombin related to the anticoagulant protein produced by leeches. By reversibly binding to thrombin, bivalirudin stops the conversion of fibrinogen to fibrin and inhibits platelet aggregation.
The anticoagulant effect begins within a few minutes of intravenous administration. The clotting time, activated partial thromboplastin time (APTT), prothrombin time and thrombin time are all increased. Bivalirudin is given as a bolus dose followed by an infusion. It has a half-life of approximately 25 minutes, with most of the dose being metabolised into amino acids. As 20% of the dose is excreted unchanged in the urine impaired renal function prolongs the half-life.
An early study of bivalirudin found that it caused less bleeding but had no greater efficacy than high-dose heparin in preventing ischaemic complications in patients having coronary angioplasty.1 Development of the drug did not proceed, however when the results were reanalysed several years later they showed a statistical advantage for bivalirudin.2 As the drugs used during the procedure had changed in the intervening years, there was a need to evaluate bivalirudin with the new approaches.
The REPLACE-2 trial randomised 6010 patients to receive bivalirudin or heparin plus a glycoprotein IIb/IIIa inhibitor. All patients also received aspirin and the use of clopidogrel was encouraged. Analysis at 30 days revealed that 7.6% of the bivalirudin group had died, had an infarction or needed urgent revascularisation. In the heparin/glycoprotein inhibitor group 7.1% of the patients reached the same end point. While the two approaches had similar efficacy, bivalirudin significantly reduced major bleeding. Major bleeding occurred in 4.1% of the patients given heparin and a glycoprotein inhibitor compared with 2.5% of the bivalirudin group.3
The patients in REPLACE-2 were followed up for a year. After six months there were fewer deaths in the bivalirudin group, but more myocardial infarctions and revascularisations. Although the mortality with bivalirudin was lower after 12 months it was not significantly different from the mortality with heparin.4
In addition to bleeding, patients may develop back pain. Unlike heparin, bivalirudin does not cause an immune thrombocytopenia, but it has been associated with thrombocytopenia.
Although bivalirudin causes less bleeding than heparin and a glycoprotein inhibitor, its role in therapy probably requires further study. The higher cost of bivalirudin will also need to be considered before it can replace heparin in general use.
- Hirulog angioplasty study investigators. Treatment with bivalirudin (Hirulog) as compared with heparin during coronary angioplasty for unstable or postinfarction angina. N Engl J Med 1995;333:764-9. .
- Bivalirudin angioplasty study investigators. Bivalirudin versus heparin during coronary angioplasty for unstable or postinfarction angina. Am Heart J 2001;142:952-9. .
- REPLACE-2 investigators. Bivalirudin and provisional glycoprotein IIb/IIIa blockade compared with heparin and planned glycoprotein IIb/IIIa blockade during percutaneous coronary intervention. JAMA 2003;289:853-63.
- REPLACE-2 investigators. Long-term efficacy of bivalirudin and provisional glycoprotein IIb/IIIa blockade vs heparin and planned glycoprotein IIb/IIIa blockade during percutaneous coronary revascularization. JAMA 2004;292:696-703 .