1. Major Bleeding Is Associated With Increased One-Year Mortality and Ischemic Events in Patients With ACS: Results From the ACUITY Trial Steven V. Manoukian, Frederick Feit, Steven R. Steinhubl, Michele D. Voeltz, George D. Dangas, Ramin Ebrahimi, Roxana Mehran, and Gregg W. Stone Emory University School of Medicine, Atlanta, GA; New York University School of Medicine, New York, NY; University of Kentucky, Lexington, KY; Columbia University Medical Center and The Cardiovascular Research Foundation, New York, NY; University of California Los Angeles and the Greater Los Angeles VA Medical Center, Los Angeles, CA

2. ●The ACUITY Trial randomized 13,819 patients with moderate and high-risk NSTE-ACS. Moderate- high risk ACS Angiography within 72h Aspirin in all Clopidogrel dosing and timing per local practice UFH or Enoxaparin + GP IIb/IIIa Bivalirudin BivalirudinAlone R* Medical management PCI CABG STUDY DESIGN

3. ACUITY Primary Results – 30 Days P NI = 0.011 P Sup = 0.32 P NI <0.001 P Sup <0.001 P NI <0.001 P Sup = 0.015

4. ACUITY Primary Results – 1 Year

5. ●Major bleeding is a significant complication of acute coronary syndromes (ACS). ●Major bleeding is associated with increased 30- day mortality and ischemic event rates. ●Bivalirudin alone results in lower rates of major bleeding vs. heparin + GPI strategies. ●We evaluated the impact of major bleeding on 1- year outcomes in patients with ACS from the ACUITY Trial. BACKGROUND & OBJECTIVES

6. Baseline Characteristics Major Bleeding (N=645) No Major Bleeding (N=13,174) P-value Age (median [range], yrs) 69 (37, 95)62 (20, 93)<0.0001 Female 49.329.1<0.0001 Weight (median [IQR], kg) 79 (68, 92)84 (73, 95)<0.0001 Diabetes 34.527.80.0002 Hypertension 73.266.70.0006 Hyperlipidemia 53.357.40.04 Current smoker 24.829.30.02 Prior MI 29.131.40.23 Prior PCI 29.839.3<0.0001 Prior CABG 17.717.90.90 Baseline CrCl <60 mL/min 37.218.2<0.0001 CKMB/Troponin  68.059.0<0.0001

7. Major Bleeding and 30-Day Event Rates P<0.0001 for all

8. 30-Day Major Bleeding by Treatment P<0.001

9. Major Bleeding and 1-Year Event Rates P<0.0001 for all

10. Major Bleeding and 30-Day Mortality

11. Predictors of 30-Day Major Bleeding

12. Predictors of 1-Year Mortality

13. CONCLUSIONS ●645 patients (4.7%) had major bleeding by 30 days. ●Major bleeding is an independent predictor of one-year mortality and is associated with increased rates of ischemic events at one year in patients with ACS. ●Treatment with bivalirudin monotherapy significantly lowers rates of bleeding compared to treatment with heparin + GPI.