Safety and Bleeding Rates

Significantly Less Major and Minor Bleeding Consistent Across Angiomax® (bivalirudin) Trials^1,2

Major Bleeding^1-4

• Thrombolysis in Myocardial Infarction (TIMI) criteria major bleeding in REPLACE-2 was 0.6% for ANGIOMAX with "provisional" glycoprotein (GP) IIb/IIIa vs 0.9% for heparin + GP IIb/IIIa (P = .30)¹

Minor Bleeding^1,3

• TIMI minor bleeding in REPLACE-2 was 1.3% for ANGIOMAX with "provisional" GP IIb/IIIa vs 3.0% for heparin + GP IIb/IIIa (P<.001)¹

*IN REPLACE-2: 93% of ANGIOMAX patients received ANGIOMAX monotherapy.¹

†	IN THE ACUITY ANGIOMAX-ALONE GROUP: 91% of PCI patients received ANGIOMAX monotherapy.2

Heparin(s) = unfractionated heparin (UFH) or enoxaparin
^‡ANGIOMAX monotherapy = ANGIOMAX monotherapy with GP IIb/IIIa reserved for severe breakthrough ischemia and procedural complications during PCI^2
§Important Bleeding Definitions

Significantly Reduced Bleeding Complications

With ANGIOMAX, significantly more patients will go home from percutaneous coronary intervention(PCI) without bleeding complications1 Sheaths can be removed 2 hours after ANGIOMAX discontinuation in most patients, reducing access-site complications|| 5-7

Intent-to-treat population in REPLACE-2 and ACUITY PCI subgroup.
^||Sheath removal has not been studied in dialysis-dependent patients. Follow standard hospital protocol for this population.

Important Bleeding Definitions

Major Bleed

Defined in REPLACE-2 as intracranial or retroperitoneal bleeding; transfusion of 2 or more units of blood/blood products; a fall in hemoglobin of >4 g/dL, whether or not bleeding site was identified; clinically overt blood loss (spontaneous or nonspontaneous) with a fall in hemoglobin of >3 g/dL.¹

Defined in ACUITY as non-CABG intracranial, retroperitoneal, or intraocular bleeding; access-site hemorrhage requiring intervention; >5-cm diameter hematoma; reduction in hemoglobin concentration of >4 g/dL without an overt source of bleeding, reduction in hemoglobin concentration of >3 g/dL with an overt source of bleeding; use of any blood-product transfusion.²

TIMI-defined as intracranial bleeding or bleeding associated with hemoglobin decrease of >5 g/dL (or a hematocrit decrease of 15%).⁸

Minor Bleed

Defined in REPLACE-2 as observed bleeding that did not meet the criteria for a major bleed.¹

Defined in ACUITY as all bleeding other than clinically significant bleeding.³

TIMI-defined as bleeding that was spontaneous and observed as gross hematuria or hematemesis; or observed blood loss (spontaneous or nonspontaneous) with a decrease in hemoglobin of >3 g/dL (or a hematocrit decrease of >10%); or a decrease in hemoglobin of >4 g/dL (or a hematocrit decrease of 12%) with no identifiable bleeding site.⁸

Safety Information

Adverse events observed in clinical trials were similar between patients treated with ANGIOMAX and the control groups.⁹ In the REPLACE-2 trial, similar adverse events were reported with similar frequencies in both treatment groups and were typical of events seen in most PCI trials. The most frequent treatment-emergent events for ANGIOMAX with "provisional" GP IIb/IIIa vs heparin plus GP IIb/IIIa were back pain, angina pectoris, pain, hypotension, and nausea.

REPLACE-2 Treatment-Emergent Adverse Events Other Than Bleeding Occurring in >2% of Patients in Either Treatment Group (Safety Population)

In the Bivalirudin and Angioplasty Trial (BAT), 82% of 2161 patients treated with ANGIOMAX and 83% of 2151 heparin-treated patients experienced at least one treatment-emergent adverse event. The most frequent treatment-emergent events for ANGIOMAX vs heparin were back pain, pain, nausea, headache, and hypotension.⁹

BAT Adverse Events Occurring in >5% of Patients in Either Treatment Group

Safety Considerations

ANGIOMAX with provisional use of glycoprotein IIb/IIIa inhibitor is indicated for use as an anticoagulant in patients undergoing percutaneous coronary intervention (PCI), and in patients with or at risk for heparin-induced thrombocytopenia and thrombosis syndrome (HIT/HITTS) undergoing PCI. ANGIOMAX is intended for use with aspirin and has been studied only in patients receiving concomitant aspirin. ANGIOMAX is contraindicated in patients with active major bleeding or hypersensitivity to ANGIOMAX or its components. The most common (10%) adverse events for ANGIOMAX were back pain, pain, nausea, headache, and hypotension. An unexplained fall in blood pressure or hematocrit, or any unexplained symptom, should lead to serious consideration of a hemorrhagic event and cessation of ANGIOMAX administration. Please see complete prescribing information.