ACUITY: Death, MI, revascularizationfor ischemia, or major bleeding by 30 days

11.7

10.1

11.8

0

5

10

15

Heparin +GPI IIb/IIIa

Bivalirudin +GPI IIb/IIIa

Bivalirudinalone

p = 0.015 for superiority of bivalrudin alone vs. hep+GPIp < 0.001 for non-inferiority of hep+GPI vs. bival+GPI

Stone GW, et al. N Engl J Med 2006;355:2203-16.

%

Primary Endpoint Measures (ITT) — 30 DaysUFH/Enoxaparin + GPI vs. Bivalirudin Alone

Primary Endpoint

Bivalirudin Alone

UFH/Enoxaparin + GPI

p Value

Noninferior

p Value

Superior

Net clinical outcome

10.1% 11.7% < 0.001 0.015

Ischemic composite

7.8% 7.3% 0.01 0.32

Major bleeding

3.0% 5.7% < 0.001 < 0.001

Presented at ACC.07 and Stone GW et al. N Engl J Med 2006;355:2203-16.

GPI = glycoprotein IIb/IIIa inhibitor; ITT = intention to treat; UFH = unfractionated heparin.

Kaplan-Meier Curves for Mortalityin Patients With or Without Major Bleeding

Manoukian S et al. J Am Coll Cardiol 2007;49:1362-8.

ACUITY Trial Treatment Strategy

UFH or Enoxaparin +

GPI

Bivalirudin + GPI

Bivalirudin Alone

PCI (%) 2,561

(55.6)

2,609

(56.7)

2,619

(56.8%)

CABG Surgery (%)

549

(11.9)

499

(10.8)

491

(10.6)

Medical Management (%)

1,493

(32.4)

1,496

(32.5)

1,502

(32.6)

UFH = unfractionated heparin; GPI = glycoprotein IIb/IIIa inhibitor; PCI = percutaneous coronary intervention; CABG = coronary artery bypass graft. Stone GW et al. N Engl J Med 2006;355:2203-16.

1-Year ACUITY Trial ResultsPCI Cohort

In moderate- to high-risk ACS patients undergoing PCI,

bivalirudin alone vs. heparin + GP IIb/IIIa inhibitor led to:

• Significant ↓bleeding at 30 days with bivalirudin alone• Comparable composite endpoint of ischemia/mortality at 1 year• Mortality at 1 year not dependent on timing of clopidogrel

• In patients already on heparin, switching to bivalirudin is safe and effective, leading to similar reductions in major bleeding (~50% ) and 1-year outcomes as bivalirudin alone

• PCI patients with major bleed experience significantly longer LOS (5 vs. 3 days; p <0.0001) than patients without major bleeds• A strong association between early bleeding and late mortality

ESC ‘07

ACS = acute coronary syndrome; GP = glycoprotein; LOS = length of stay; PCI = percutaneous coronary intervention.

1-Year ACUITY Trial Conclusion

These results suggest bivalirudin monotherapy should be the preferred adjunctive antithrombotic strategy in moderate- and high-risk acute coronary syndrome patients undergoing percutaneous coronary intervention and add to the evidence on the relationship between early bleeding and long-term outcome.