Aggrastat® is a reversible antagonist of fibrinogen that binds to the glycoprotein (GP) IIb/IIIa receptor, the major platelet surface receptor involved in platelet aggregation.
Aggrastat® has a half-life of approximately 2 hours and is cleared primarily by the kidneys, predominantly as unchanged drug.
Following discontinuation of an infusion of Aggrastat®, ex vivo platelet aggregation returns to near baseline within 4 to 8 hours in approximately 90% of patients with coronary artery disease. There is no effect on clearance of tirofiban by sex, race, age, or hepatic impairment.
Thrombus and bleeding management is an important consideration in several clinical situations including interventional procedures. T-TAS (Total Thrombus formation Analysis System) is an automated microchip flow chamber system for the quantitative analysis of the thrombus formation process under blood flow conditions. T-TAS reproduces the in vivo thrombus formation process in an ex vivo system that uses the same substances that stimulate thrombus formation under physiological conditions.
No antiplatelet therapy
DAPT
DAPT + Aggrastat®
DAPT = dual antiplatelet therapy
Platelet thrombus formation using T-TAS plus PL-chip in whole blood samples from a healthy subject.
Video-recorded images of the PL-chip in whole blood from an antiplatelet naïve subject, and with DAPT pre- and post-tirofiban. Blood samples were collected in benzylsulfonyl-D-Arg-Pro-4-amidinobenzylamide (BAPA).*
No antiplatelet therapy
DAPT
DAPT + Aggrastat®
DAPT = dual antiplatelet therapy
Fibrin-rich platelet thrombus formation using T-TAS plus AR-chip in whole blood samples from healthy patients.
Video-recorded images of the AR-chip in whole blood from an antiplatelet naïve subject, and with DAPT pre and post-tirofiban are shown. Blood samples were collected in 3.2 % citrate tubes.*
| PL CHIP Arterial flow shear =1500s-1 |
AR CHIP Venous flow shear = 600s-1 |
||||
|---|---|---|---|---|---|
| Occlusion start time (min, secs) | AUC | Occlusion start time (min, secs) | Occlusion time (min) |
AUC | |
| Antiplatelet Naive | 1:29 | 395 | 6:15 | 8:25 | 1821 |
| DAPT (ASA 81 mg + clopidogrel 75 mg) |
4:42 | 231 | 5:38 | 7:26 | 1890 |
| DAPT + tirofiban | 10:00 | 21 | 18:28 | 20:00 | 835 |
DAPT = dual antiplatelet therapy; ASA = aspirin; AUC = area under the curve
* Methods. Blood was drawn from an antiplatelet naïve subject into Benzylsulfonyl-D-argininyl-prolyl-4-amidinobenzylamide (BAPA) and sodium citrate blood collection tubes and measured using the RUO T-TAS® plus system. A second blood collection was then performed in same subject following 3 days of DAPT with ASA 81 mg and clopidogrel 75 mg and blood was processed. Additional BAPA and citrate tubes were collected during a second blood draw and incubated with 100 ng/mL of tirofiban for 15 minutes and then processed. The results from both PL chip and AR chip analysis are included in Table (above).
1. Mardikar HM et al. Am Heart J 2007; 154:344e1-344e5
2. Danzi GB et al. AM J Cardiol 2006; 97:489-493
3. Credit. Kevin P. Bliden, Udaya S. Tantry, Paul A. Gurbel; Sinai Center for Thrombosis Research and Drug Development, Sinai Hospital of Baltimore, MD
Aggrastat® is indicated to reduce the rate of thrombotic cardiovascular events (combined endpoint of death, myocardial infarction, or refractory ischemia/repeat cardiac procedure) in patients with non-ST elevation acute coronary syndrome (NSTE-ACS).
For additional information, refer to the full Prescribing Information.
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