1. Predictors of Major Vascular Access Site Complications in Patients with Acute Coronary Syndromes Undergoing Percutaneous Coronary Intervention: Insights from the ACUITY Trial Steven V Manoukian, Reza Fazel, Timothy A. Sanborn, Ramin Ebrahimi, Frederick Feit, Martial Hamon, Michele D. Voeltz, George D. Dangas, Jeffrey W. Moses, Spencer B. King III, Harvey 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 vascular access site complications were defined as: –access site bleeding requiring invasive intervention, or –hematoma >5cm. 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) Stone GW et al. Am Heart J 2004;148:764–75. Medical management PCI N=7,789 56.4% CABG

5. Background: ACUITY PCI: Major Bleeding by Treatment Strategy P<0.0001 Stone GW et al. Lancet 2007;369:907-19. P<0.0001

6. Background: REPLACE-2: Predictors of Major Vascular Complications in PCI Background: Major vascular complications (MVC) associated with significant morbidity in PCI. Methods: MVC defined as vascular access site major bleeding or surgical repair. Results: MVC rate 1.9%, less for BIV vs. H+GPI (1.17% vs. 2.61%, unadjusted OR 0.44, p<0.0001). Conclusions: Altering treatment strategy with regard to the 3 modifiable factors may reduce MVC in PCI. Predictors of Major Vascular Complications in PCI (n=5667, 94% of R2) VariableOdds Ratio95% CIP-value Treatment group (H + GPI vs. BIV)2.381.61 - 3.82<0.0001 Vascular closure device (n= 1400)1.851.18 - 2.900.007 Sheath dwell time (in hours)1.061.03 - 1.09<0.0001 GFR <60 ml/min/1.73 m 2 1.701.08 - 2.680.02 Female gender2.301.53 - 3.46<0.0001 Fazel R, Voeltz MD, Feit F, Attubato MJ, Rab ST, Samady H, Rao SV, Manoukian SV. ACC 2007. Stepwise logistic regression. c-statistic 0.71. Test for goodness-of-fit indicated satisfactory fit.

7. Background and Methods: Vascular Complications in PCI Major vascular assess site complications are associated with significant morbidity in ACS and PCI. We determined the baseline and procedural predictors of major vascular complications in patients with ACS undergoing PCI via the femoral approach. Manoukian SV et al. TCT 2007.

8. Results: ACUITY PCI: Management Strategy 56.4% 11.1% 32.5% CABG (n=1,539) Medical Rx (n=4,491) PCI (n=7,789) Femoral access PCI n = 6879 Major vascular complication n = 179 Manoukian SV et al. TCT 2007.

9. Results: ACUITY PCI: Major Vascular Complications by Treatment Strategy P<0.0001 P=ns Manoukian SV et al. TCT 2007.

10. Age ≥75 years 1.97 (1.34-2.88) 0.0005 Baseline CrCl <60 mL/min 1.65 (1.13-2.43) 0.01 Female (vs male) 2.20 (1.59-3.03) <0.0001 No Prior PCI 1.75 (1.23-2.48) 0.002 Prior CABG 1.48 (1.00-2.20) 0.05 Randomization to UFH/Enox + GPI (vs. bivalirudin) 4.05 (2.40-6.85) <0.0001 Odds ratio ±95% CI P-value OR (95% CI) Results: ACUITY PCI: Predictors of Major Vascular Complications Manoukian SV et al. TCT 2007.

11. Results: The ACUITY Trial PCI Population (n=7789) Vascular Complications in PCI In patients with ACS undergoing PCI via the femoral approach, independent predictors of MVC include: age ≥75 years, creatinine clearance <60 mL/min, female sex, prior PCI, prior CABG, and use of H+GPI (vs. BIV). Altering treatment strategy with regard to the modifiable factor (use of H+GPI) may reduce the risk of MVC. Manoukian SV et al. TCT 2007.