ANGIOMAX Efficacy in PCI Consistent Across
Landmark Trials

Proven efficacy versus heparin + GP IIb/IIIa in preventing ischemic events at 30 days while significantly reducing major bleeds, an independent predictor of mortality^1-3

• Demonstrated in REPLACE-2, the largest clinical trial ever conducted to evaluate antithrombotics in percutaneous coronary intervention (PCI)
  (n = 6,002)^1,4

REPLACE-2¹

Clinical outcomes: Ischemic events and major bleed at 30 days in intent-to-treat population^{1 †}Important Bleeding Definitions

*IN REPLACE-2: 93% of Angiomax® (bivalirudin) patients received ANGIOMAX monotherapy.¹

Randomized Evaluation in PCI Linking ANGIOMAX to Reduced Clinical Events (REPLACE-2) trial, a prospective, double-blind, multicenter study of 6,002 patients undergoing PCI, randomized to treatment with ANGIOMAX with "provisional" platelet glycoprotein (GP) IIb/IIIa inhibitor or unfractionated heparin plus planned GP IIb/IIIa inhibitor (abciximab or eptifibatide).¹

ACUITY PCI results confirm ANGIOMAX benefits in moderate- and high-risk patients.

Proven efficacy versus heparin(s) + GP llb/llla in preventing ischemic events while significantly reducing major bleeds.^5,6

ACUITY PCI^5,6,7

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.⁵

^§The median maximum ACT among UFH patients was 239 seconds [interquartile range, 211 to 291].⁵

^||Important Bleeding Definitions

• Results in the ANGIOMAX + GP llb/llla arm (n = 2,609) vs heparin(s) + GP IIb/IIIa⁷
  — Net clinical outcome, 14.9% (P = .10)
  — Composite ischemia, 9.3% (P = .16)
  — Major bleed, 7.5% (P = .32)
• The rate of stent thrombosis was the same in ANGIOMAX-alone and heparin(s) + GP IIb/IIIa patients (1.3%, P = .99)⁷

Mortality Data Confirm ANGIOMAX Long-Term Efficacy

REPLACE-2 Mortality Results at 1 Year^4,7

P value is based on the log-rank test. Event rates for all-cause, 1-year mortality.

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

ANGIOMAX mortality results confirmed at 1 year by subgroups and treatment assignment.⁷

SUBGROUP		ANGIOMAX With “Provisional” GP IIb/IIIa (n/N)	Heparin + GP IIb/IIIa (n/N)	P value
Eptifibatide Abciximab		1.7% (28/1,634) 2.1% (28/1,312)	2.2% (36/1,638) 2.7% (36/1,323)	.317 .328
Age < 75 years Age > 75 years		1.6% (42/2,563) 3.6% (14/388)	1.7% (44/2,561) 6.9% (28/407)	.825 .039
Men Women		1.7% (37/2,200) 2.5% (19/751)	2.1% (45/2,195) 3.5% (27/773)	.367 .272
Diabetes No diabetes		2.3% (19/829) 1.7% (37/2,117)	3.9% (30/777) 1.9% (42/2,186)	.068 .672
ACS* at presentation No ACS* at presentation		1.5% (10/660) 2.0% (45/2,249)	1.8% (12/670) 2.5% (57/2,246)	.693 .227
Creatinine clearance <60 Creatinine clearance >60		4.5% (20/445) 1.5% (36/2,461)	7.1% (33/463) 1.5% (38/2,461)	.091 .815
Clopidogrel pretreatment No clopidogrel pretreatment		2.0% (50/2,555) 1.5% (6/394)	2.5% (64/2,532) 1.8% (8/434)	.169 .721
UFH pretreatment† No UFH pretreatment		2.2% (7/320) 1.9% (49/2,631)	3.3% (12/365) 2.3% (60/2,603)	.382 .262
Low molecular weight heparin (LMWH) pretreatment† No LMWH pretreatment		2.1% (6/283) 1.9% (50/2,668)	4.9% (15/308) 2.1% (57/2,660)	.071 .484
Type A/B1 lesions Type B2/C lesions		2.1% (25/1,182) 1.9% (28/1,486)	2.1% (25/1,218) 2.7% (39/1,455)	.915 .148

ACS = acute coronary syndromes
^* Defined as: angina within 48 hours or MI within 7 days.
^† Defined as: pretreatment within prior 48 hours.

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.