1. Impact of Anemia on One-Year Ischemic Events and Mortality Among Patients with Acute Coronary Syndromes Undergoing Percutaneous Coronary Intervention Steven V. Manoukian, Michele D. Voeltz, George D. Dangas, Frederick Feit, Reza Fazel, Ramin Ebrahimi, Martial Hamon, A. Michael Lincoff, Jeffrey W. Moses, Spencer B. King III, Harvery D. White, E. Magnus Ohman, Roxana Mehran, Gregg W. Stone, on behalf of the ACUITY Investigators

2. Disclosures Consultant: BMS, Guerbet, Sanofi-Aventis, Schering- Plough, The Medicines Co. Grant Support: Guerbet, The Medicines Co. Lecture honoraria: Guerbet, The Medicines Co. Manoukian SV et al. TCT 2007.

3. Background and Methods: Study Design and Definitions The ACUITY Trial randomized 13,819 patients with moderate and high-risk NSTE-ACS to: –heparin/enoxaparin + GPIIb/IIIa inhibitor, –bivalirudin + GPIIb/IIIa inhibitor, or –bivalirudin alone. Major bleeding (non-CABG-related) was defined as: –intracranial, intraocular, or retroperitoneal, –access site with intervention, hematoma >5cm, –hgb drop >3g/dL with source or >4g/dL without source, –reoperation, –transfusion. Stone GW et al. NEJM 2006;355:2203-16.

4. Moderate- high risk ACS Background and Methods: ACUITY: Study Design Angiography within 72h Aspirin in all Clopidogrel dosing and timing per local practice UFH or Enoxaparin + GP IIb/IIIa Bivalirudin + GP IIb/IIIa Bivalirudin Alone R* *Stratified by pre-angiography thienopyridine use or administration Moderate and high-risk NSTE-ACS undergoing an invasive strategy (N = 13,819) Medical management PCI N=7,789 56.4% CABG Stone GW et al. NEJM 2006;355:2203-16.

5. Background: ACUITY Overall: Anemic vs. Non-Anemic Population Short-Term (30-Day) Event Rates P=<0.0001 Dangas GD, Manoukian SV, Nikolsky E et al. ESC 2007.

6. Background: ACUITY Overall: Anemic Population by Treatment P=0.74P=0.59P=0.71P=0.77P=0.81P=0.052 Short-Term (30-Day) Event Rates Dangas GD, Manoukian SV, Nikolsky E et al. ESC 2007.

7. Background: ACUITY PCI: Anemic vs. Non-Anemic Population Short-Term (30-Day) Event Rates P=<0.0001 P=0.0007 Dangas GD, Manoukian SV, Nikolsky E et al. ESC 2007.

8. Background: ACUITY PCI: Anemic Population by Treatment P=0.33P=0.90 P=0.95P=0.87 P=0.19P=0.26 Short-Term (30-Day) Event Rates Dangas GD, Manoukian SV, Nikolsky E et al. ESC 2007.

9. Background: REPLACE-2: Anemia Long-Term (1-Year) Mortality in PCI Voeltz MD, Patel AD, Feit F, Fazel R, Lincoff AM, Manoukian SV. Am J Cardiol 2007;99:1513-17. 4.3% 1.5%

10. Background: REPLACE-2: Anemia Independent Predictor of 1-Year Mortality in PCI Voeltz MD, Patel AD, Feit F, Fazel R, Lincoff AM, Manoukian SV. Am J Cardiol 2007;99:1513-17.

11. Background and Methods: Anemia in ACS Patients Undergoing PCI Baseline anemia is associated with an increased risk of short-term (30-day) ischemic complications and mortality in ACS and PCI. Anemia was defined using WHO criteria: –hgb <13 g/dL men, –hgb <12 g/dL women. We assessed the impact of anemia on rates of long- term (1-year) ischemic events and mortality in patients with ACS undergoing PCI in the ACUITY trial. Manoukian SV et al. TCT 2007.

12. Results: ACUITY PCI: Anemia Population Characteristics Non-Anemic (N=6238, 84.3%) Anemic (N=1164, 15.7%) P value Age (median [range], yrs)62 (21, 92)69 (34, 95)<0.0001 Male74.667.1<0.0001 Weight (median [IQR], kg)84 (74.9, 96.0)82 (71, 95)<0.001 Diabetes24.343.3<0.0001 Hypertension62.879.4<0.0001 Hyperlipidemia53.966.3<0.0001 Current smoker33.616.8<0.0001 Prior MI29.435.0 0.0001 Prior PCI36.251.7<0.0001 Prior CABG16.225.0<0.0001 Hemoglobin (mean)14.511.7<0.0001 Renal insufficiency*15.434.7<0.0001  CKMB/Troponin  66.059.4<0.0001 * creatinine clearance <60 mL/minManoukian SV et al. TCT 2007.

13. Results: ACUITY PCI: Anemic vs. Non-Anemic Population Long-Term (1-Year) Ischemic Event Rates P=<0.0001 Manoukian SV et al. TCT 2007.

14. Results: ACUITY PCI: Anemic vs. Non-Anemic Population Long-Term (1-Year) Mortality P=<0.0001 Manoukian SV et al. TCT 2007.

15. Results: ACUITY PCI: Anemic Population by Treatment Long-Term (1-Year) Event Rates HR ±95% CI Composite Ischemia1.04 (0.77-1.39) HR (95% CI) Bivalirudin BetterUFH/Enox+ IIb/IIIa Better Mortality0.99 (0.56-1.76) Manoukian SV et al. TCT 2007.

16. Results: ACUITY PCI: Independent Predictors of 1-Year Mortality HR ±95% CIHR (95% CI) Age (≥75 years)2.67 (1.95-3.66) Anemia1.58 (1.18-2.13) Baseline CrCl <60 mL/min1.62 (1.17-2.24) Prior CVA1.43 (1.07-1.90) CKMB/Troponin+2.14 (1.56-2.93) ECG changes1.54 (1.18-2.01) History of CAD1.95 (1.45-2.62) Diabetes1.79 (1.39-2.31) Manoukian SV et al. TCT 2007.

17. Conclusions: Anemia and Long-term (1-Year) Outcomes in Patients with ACS Undergoing PCI Anemia is not uncommon in patients with: –ACS (16.9%), and in patients with –ACS undergoing PCI (15.7%). Anemia is associated with a significant increase in rates of long-term (1-year) ischemic events. Anemia is associated with an over 2-fold increase in rates of long-term (1-year) mortality and is an independent predictor of long-term (1-year) mortality in patients with ACS undergoing PCI. Manoukian SV et al. TCT 2007.