1. Michael A. Nelson, MD 1 Michele D. Voeltz, MD 1 Frederick Feit, MD 2 A. Michael Lincoff, MD 3 Steven V. Manoukian, MD 1 1 Emory University School of Medicine 2 New York University School of Medicine 3 Cleveland Clinic Foundation Elderly Patients with Major Bleeding or Need for Transfusion Complicating Percutaneous Coronary Intervention Have an Increased Risk of 30-Day and 1-Year Mortality

2. Presenter Disclosure Information Michael A. Nelson: NoneMichael A. Nelson: None Michele D. Voeltz: NoneMichele D. Voeltz: None Frederick Feit: The Medicines Co.-Frederick Feit: The Medicines Co.-Consultant (significant) A. Michael Lincoff: The Medicines Co.-Research Support (significant), Honoraria (modest)A. Michael Lincoff: The Medicines Co.-Research Support (significant), Honoraria (modest) Steven V. Manoukian: The Medicines Co.-Research Support, Consultant, Speaker (modest), sanofi-aventis/BMS: Consultant (modest)Steven V. Manoukian: The Medicines Co.-Research Support, Consultant, Speaker (modest), sanofi-aventis/BMS: Consultant (modest)

3. Elderly Patients with Major Bleeding or Transfusion: Background Elderly patients have an increased risk of major bleeding and transfusion when undergoing percutaneous coronary intervention (PCI). Despite these risks, the effect of major bleeding and transfusion on mortality in the elderly is unknown. We evaluated outcomes in elderly patients undergoing PCI from the REPLACE-2 Trial.

4. 6010 Urgent or elective PCI patients 6010 Urgent or elective PCI patients Aspirin Clopidogrel Stent Aspirin Clopidogrel Stent 2999 3011 Heparin 65 U/kg Heparin Endpoints 30-day Death MI Revasc Hemorrhage Economics 6, 12m follow up Endpoints 30-day Death MI Revasc Hemorrhage Economics 6, 12m follow upBivalirudin Provisional GPIIb/IIIa Bivalirudin AbciximaborEptifibatideAbciximaborEptifibatide Lincoff AM, et al. JAMA 2003; 289: 853-863. Background: The REPLACE-2 Trial Trial Design

5. Background: The REPLACE-2 Trial Primary Endpoint at 30 Days % of patients p = 0.324 p = 0.255 p = 0.430 p = 0.435 p < 0.001 Lincoff AM, et al. JAMA 2003; 289: 853-863. Major bleeding Intracranial, intraocular, or retroperitoneal Observed bleed with fall in Hgb >3g/dL No observed bleed with fall in Hgb >4g/dL Transfusion  2 units PRBC or whole blood

6. Background: The REPLACE-2 Trial Mortality by Age = Elderly, >75 (N=805) = Not Elderly, <75 (N=5196) p<0.0001p=0.0001p<0.0001 Mortality Voeltz MD, et al. Circulation 2005;112(17):II-613.

7. Background: The REPLACE-2 Trial Bleeding and Transfusion by Age p<0.0001 Voeltz MD. et al. Circulation 2005;112(17):II-613. = Elderly, >75 (N=805) = Not Elderly, <75 (N=5196)

8. Elderly Patients with Major Bleeding or Transfusion: Hypothesis Elderly patients with major bleeding or transfusion complicating PCI have an increased risk of mortality.

9. Elderly Patients with Major Bleeding or Transfusion: Methods We reviewed the REPLACE-2 Trial in order to evaluate the impact of major bleeding and transfusion on the risk of 30-day, 6-month and 1-year mortality in elderly patients undergoing PCI. Elderly patients were defined as > 75 years of age. Major Bleeding (30-Days) was defined as: –Intracranial, intraocular, or retroperitoneal hemorrhage –Overt blood loss with drop in Hgb >3g/dL –Any decrease in Hgb >4g/dL –Transfusion of >2 pRBC’s or whole blood Transfusion (30-Days) was defined as any transfusion of pRBC’s or whole blood.

10. Results: Baseline Characteristics by Age Elderly >75 years (N=805) Not Elderly  75 years (N=5196) p-value Age (Mean, Years)79.360.0 Women39.3%23.5%<0.01 Caucasian94.3%92.2%0.04 Prior CABG23.9%17.5%<0.01 CVA3.9%2.1%0.01 Hypertension75.4%65.7%<0.01 CHF13.3%6.0%<0.01 Weight (kg)77.589.0<0.01 Body Mass Index (kg/m 2 )27.330.0<0.01 Prior MI32.6%37.7%0.01 Tobacco Use (last 1y)6.1%29.7%<0.01 Baseline Hemoglobin (g/dL)12.913.8<0.01 Creatinine Clearance (cc/min)57.4100.2<0.01

11. Results: Mortality with Major Bleeding by Age = Elderly, >75 (N=54) = Not Elderly, <75 (N=139) p<0.01 p<0.02p<0.01 Mortality Nelson MA, et al. AHA 2006.

12. Results: Mortality with Transfusion by Age = Elderly, >75 (N=40) = Not Elderly, <75 (N=86) p<0.02 Mortality Nelson MA, et al. AHA 2006.

13. Results: Mortality Among Elderly by Bleeding Status = Elderly, Major Bleed (N=54) = Elderly, No Major Bleed (N=751) p<0.01 Mortality p<0.01 Nelson MA, et al. AHA 2006.

14. Results: Mortality Among Elderly by Transfusion Status = Elderly, Transfusion (N=40) = Elderly, No Transfusion (N=765) p<0.0001 Mortality p<0.0001 Nelson MA, et al. AHA 2006.

15. Results: Baseline Characteristics Among Elderly by Bleeding Status Elderly with Major Bleeding (N=54) Elderly without Major Bleeding (N=751) p-value Women53.7%38.3%0.03 Prior MI46.2%31.7%0.03 CHF22.2%12.6%0.04 Baseline Anemia56%41%0.03 Baseline Hemoglobin (g/dL)12.112.9<0.01 Creatinine Clearance (cc/min)53580.03 Weight (kg)76.277.6ns Body Mass Index (kg/m 2 )27.827.3ns Prior Diabetes Mellitus31.528.8ns Prior CABG31.5%23.4%ns CVA5.7%3.7%ns Hypertension77.8%75.3%ns Caucasian88.9%94.7%ns Tobacco Use (last 1y)3.8%6.3%ns

16. Elderly Patients with Major Bleeding or Transfusion: Conclusions Elderly patients undergoing PCI have an increased risk of major bleeding, transfusion, and mortality, compared to younger patients. Among patients with major bleeding or transfusion, the elderly have an increased risk of mortality. Among the elderly, major bleeding or transfusion is associated with an increased risk of mortality. Knowledge of these findings is important in the care of elderly patients undergoing PCI. Nelson MA, et al. AHA 2006.