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Safety Profile in Clinical Trials

The safety of Aggrastat® (tirofiban hydrochloride) was studied in the PRISM, PRISM-PLUS, and RESTORE clinical trials.

In these studies, 1946 patients received Aggrastat® in combination with heparin and 2002 patients received Aggrastat® alone for about 3 days.

In clinical studies with the recommended regimen (25 mcg/kg bolus followed by a 0.15 mcg/kg/min maintenance infusion), Aggrastat® was administered in combination with aspirin, clopidogrel and heparin or bivalirudin to over 8000 patients for typically ≤ 24 hours.

Aggrastat Pharmacy Clinical Trial Experience


The incidences of major and minor bleeding using the TIMI criteria in the PRISM-PLUS study are shown below.

TIMI Major and Minor Bleeding in PRISM-PLUS

(TIMI Criteria)‡ §
Aggrastat® + Heparin
Heparin alone
Major Bleeding 1.4% 0.8%
Minor Bleeding 10.5% 8.0%
Transfusions 4.0% 2.8%

* 0.4 mcg/kg/min initial infusion; 0.10 mcg/kg/min maintenance infusion.
‡ Major = Hemoglobin drop of > 5.0 g/dL with or without an identified site, intracranial hemorrhage, or cardiac tamponade.
§ Minor = Hemoglobin drop of > 3.0 g/dL with bleeding from a known site, spontaneous gross hematuria, hematemesis or hemoptysis.

TIMI Major Bleeding Associated with Percutaneous Procedures in PRISM-PLUS

  Aggrastat® + Heparin Heparin alone
  n % n %
Prior to Procedures 773 0.3 797 0.1
Following Angiography 697 1.3 708 0.7
Following PTCA 239 2.5 236 2.2

The incidence rates of TIMI major bleeding in patients undergoing coronary artery bypass graft surgery (CABG) in PRISM-PLUS within one day of discontinuation of Aggrastat® were 17% on Aggrastat® plus heparin (N=29) and 35% on heparin alone (N=31).

Rates of major bleeds (including any intracranial, intraocular or retroperitoneal hemorrhage, clinically overt signs of hemorrhage associated with a drop in hemoglobin of > 3 g/dL or any drop in hemoglobin by 4 g/dL, bleeding requiring transfusion of ≥ 2 U blood products, bleeding directly resulting in death within 7 days or hemodynamic compromise requiring intervention) were consistent with the rates observed in subjects administered the PRISM-PLUS regimen of Aggrastat®.

There was a trend toward greater bleeding in ST segment elevation myocardial infarction (STEMI) patients treated with fibrinolytics prior to administration of Aggrastat® using the recommended regimen during rescue PCI.

High-dose bolus plus shortened infusion Aggrastat® regimen provided similar efficacy and safety in SAVI-PCI compared with longer-infusion regimens.

SAVI-PCI compared clinical outcomes at 48 hours post-PCI (or hospital discharge, whichever came first) after treatment with short duration Aggrastat® or two different longer-infusion regimens of Aggrastat® or Integrilin® in patients undergoing PCI for elective or NSTE-ACS indications. Clinical outcomes (death, periprocedural myonecrosis, uTVR) and major bleeding (REPLACE-2) were reported.

Non-CABG-related bleeding within 48 hours post-PCI or hospital discharge

SAVI-PCI Safety Endpoints: REPLACE-21,2

Short infusion
Long infusion
Long infusion
REPLACE-21,2 major0 (0.0%)4 (3.2%)1 (0.5%)
REPLACE-21,2 minor16 (7.7%)13 (10.5%)19 (9.4%)
REPLACE-21,2 major or
16 (7.7%)15 (12.1%)†20 (9.9%)

CABG=Coronary Artery Bypass Graft; REPLACE-2=Randomized Evaluation in PCI Linking Angiomax to Reduced

Clinical Events

The rate of REPLACE-2-defined major bleeding was significantly lower for Aggrastat® short infusion versus Aggrastat® long infusion (p=0.0093) and Integrilin® long infusion versus Aggrastat® long infusion (p=0.0394). Aggrastat® short infusion versus Integrilin® long infusion was statistically non-significant (p>0.05). The rate of REPLACE-2-defined minor bleeding or combined endpoint of REPLACE-2 major and minor bleeding between Aggrastat® short infusion, Aggrastat® long infusion, and Integrilin® long infusion arms was statistically non-significant (p>0.05 for all comparisons).

†Two patients in the Aggrastat® long infusion group experienced both a minor and major bleeding event at different timepoints, but prior to discharge.

REPLACE-2 Major Bleed: intracranial, intraocular, or retroperitoneal; overt blood loss with hemoglobin decrease 3 g/dL; any hemoglobin decrease 4 g/dL; transfusion of 2 U blood products. REPLACE-2 Minor Bleed: overt bleeding not meeting criteria for major bleeding.

SAVI-PCI Safety Endpoints: TIMI Bleeding1-3

Short infusion
Long infusion
Long infusion
TIMI major1-30 (0.0%)2 (1.6%)1 (0.5%)
TIMI minor1-31 (0.5%)3 (2.4%)1 (0.5%)
TIMI major or minor1-31 (0.5%)5 (4.0%)2 (1.0%)
Thrombocytopenia*1-30 (0.0%)1 (0.8%)3 (1.5%)

TIMI=Thrombolysis in Myocardial Infarction

The rate of the sum of TIMI major and minor bleeding was significantly lower for Aggrastat® short infusion versus Aggrastat® long infusion (p=0.0155). All other comparisons were statistically non-significant (p>0.05). The rates of thrombocytopenia was statistically non-significant between groups (p>0.05 for all comparisons). None of the thrombocytopenia events were severe (<50,000 cells/µL).

*Thrombocytopenia was assessed as a platelet count of <100,000 cells/µL, further divided into either severe thrombocytopenia (<50,000 cells/µL) or profound thrombocytopenia (<20,000 cells/µL) if applicable.

TIMI Major Bleeding: any intracranial bleeding (excluding microhemorrhages <10 mm evident only on gradient-echo MRI), clinical overt signs of hemorrhage associated with a decrease in hemoglobin of ≥5 g/dL, fatal bleeding (defined as a bleeding event that directly results in death within 7 days). TIMI Minor Bleeding: clinically overt (including imaging), resulting in decrease in hemoglobin concentration of 3 to <5 g/dL.


  1. Feit F et al. Am J Cardiol 2007;100:1364-9.
  2. Lincoff AM et al. JAMA 2003;289:853-63.
  3. Bovill EG et al. Ann Intern Med 1991;115:256-65.
Important Safety Information


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).


  • Known hypersensitivity to any component of Aggrastat®.
  • History of thrombocytopenia with prior exposure to Aggrastat®.
  • Active internal bleeding, or history of bleeding diathesis, major surgical procedure or severe physical trauma within the previous month.

Warnings and Precautions:

  • Aggrastat® can cause serious bleeding. Most bleeding associated with Aggrastat® occurs at the arterial access site for cardiac catheterization. Minimize the use of traumatic or potentially traumatic procedures such as arterial and venous punctures, intramuscular injections, nasotracheal intubation, etc. Concomitant use of fibrinolytics, anticoagulants and antiplatelet drugs increases the risk of bleeding. If bleeding cannot be controlled, discontinue Aggrastat®.
  • Thrombocytopenia: discontinue Aggrastat® and heparin.

Adverse Reactions:

  • Bleeding is the most commonly reported adverse reaction.

For additional information, refer to the full Prescribing Information.

You are encouraged to report negative side effects of prescription drugs to the FDA.

Visit www.FDA.gov/medwatch
or call 1-800-FDA-1088.