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.
Aggrastat (Merck Sharp & Dohme)
50 mL glass vials containing 0.25 mg/mL
500 mL plastic containers containing 0.05 mg/mL
Approved indications: unstable angina, myocardial ischaemia
Australian Medicines Handbook Section 7.2
Tirofiban inhibits platelet aggregation by blocking the glycoprotein IIb/IIIa receptor. This prevents fibrinogen binding to the platelets.1 As platelet activation leads to arterial thrombus formation, tirofiban has a potential role in acute coronary syndromes. This has been studied in two large trials.
In the PRISM study,2 3232 patients with unstable angina were randomised to receive aspirin and either tirofiban or heparin. Within 48 hours, 5.6% of the patients given heparin were dead, had a myocardial infarction or had refractory ischaemia. Only 3.8% of the patients given tirofiban reached this composite end point.
The PRISM-PLUS study3 included 1915 patients with unstable angina or non-Q wave myocardial infarction. These patients were given aspirin with heparin, or tirofiban, or both. In comparison with the heparin group, tirofiban plus heparin significantly reduced the composite end points at 7 days, 30 days and 6 months.
Tirofiban is given intravenously. After an initial infusion lasting 30 minutes, a maintenance infusion is continued for at least 48 hours. Tirofiban has a half-life of approximately two hours. It is excreted unchanged mainly in the urine, but also in the bile. The dose should be reduced in patients with renal impairment.
Bleeding is the most common complication of therapy. In the PRISM study, 2.4%of the patients given tirofiban needed a transfusion. In the PRISM-PLUS study,4% of those given heparin and tirofiban needed a transfusion. (This study was stopped because of a significant increase in deaths in patients taking tirofiban alone.) In addition to regular checks of the haemoglobin, the platelet count is also monitored as there is a risk of thrombocytopenia.
The precise role of tirofiban is unclear. As it has been approved for use with heparin, the PRISM-PLUS study deserves further examination. Dissection of the composite end points reveals that, at 6 months, the absolute reduction in death or myocardial infarction was 3% (12.3% of the tirofiban plus heparin group and 15.3% of the heparin group had died or had an infarction). The cost of purchasing this extra benefit will undoubtedly determine whether or not tirofiban becomes part of standard treatment.
- Lefkovits J. Recent advances in antiplatelet therapy. Aust Prescr 1996;19:98-101.
- The Platelet Receptor Inhibition in Ischemic Syndrome Management (PRISM) Study Investigators. A comparison of aspirin plus tirofiban with aspirin plus heparin for unstable angina. N Engl J Med 1998;338:1498-505.
- The Platelet Receptor Inhibition in Ischemic Syndrome Management in Patients Limited by Unstable Signs and Symptoms (PRISM-PLUS)Study Investigators. Inhibition of the platelet glycoprotein IIb/IIIa receptor with tirofiban in unstable angina and non-Q-wave myocardial infarction. N Engl J Med 1998;338:1488-97.