1. Allen Jeremias, Neal Kleiman, Deborah Nassif, Wen-Hua Hsieh, Michael Pencina, Kelly Maresh, Manish Parikh, Donald Cutlip, Ron Waksman, Steven Goldberg, Peter Berger, David Cohen Prevalence and Prognostic Significance of Preprocedural Cardiac Troponin Elevation Among Patients With Stable Coronary Artery Disease Undergoing Percutaneous Coronary Intervention: Results From The EVENT Registry Circulation 2008;118:632-638

2. Jeremias et al., Circulation 2008;118:632-8 Presenter Disclosure Information The EVENT Registry is supported by research grants from Schering-Plough and Millennium Pharmaceuticals None of the authors have any disclosures with respect to this work

3. Jeremias et al., Circulation 2008;118:632-8 Background Elevated cardiac troponin well established as predictor of adverse outcomes among patients with ACS Troponin elevation has been described in a number of disease states in the absence of ACS and has been shown to be associated with adverse outcomes However, troponin is not typically evaluated in patients with stable CAD To date the incidence and prognostic significance of troponin elevation among patients with stable CAD undergoing PCI is unknown

4. Jeremias et al., Circulation 2008;118:632-8 Objective To determine the prevalence of baseline troponin elevation in patients undergoing PCI for stable angina or abnormal cardiac stress test To examine the association between elevated troponin and peri-procedural ischemic complications To evaluate the long-term outcome among patients with baseline troponin elevation

5. Jeremias et al., Circulation 2008;118:632-8 Study Design The EVENT registry is a U.S. wide collaborative effort to assess “real clinical practice” by performing a prospective evaluation of unselected patients undergoing stent implantation Baseline characteristics, angiographic outcomes, post-procedural elevation of biomarkers of myocardial necrosis and clinical end points are collected prospectively by case report forms (CRF) Patients are evaluated during their index hospital admission, and 1-year after receiving the stents The population for this analysis consists of 7592 patients from 47 centers in the U.S. recruited in a total of three waves

6. Jeremias et al., Circulation 2008;118:632-8 7592 Patients 613 Excluded (STEMI) N = 6979 N=3869 N=2607 3110 Excluded (ACS) 1129 Excluded (Baseline CKMB not drawn ) 133 Excluded (Baseline CKMB >=1xULN) N=3736 Clinically Eligible 225 Excluded (Baseline cTn not available) N=2382 Analytic Cohort Study Population

7. Jeremias et al., Circulation 2008;118:632-8 Methods – Medical Therapy All patients undergoing PCI were premedicated with 325 mg aspirin, and continued indefinitely Antithrombotic regimens (heparin, bivalirudin, glycoprotein IIb/IIIa inhibitors) were at the discretion of the treating physicians A loading dose of clopidogrel (300-600 mg) was given prior to the procedure or in the catheterization laboratory (unless patients were already on clopidogrel therapy), and clopidogrel 75 mg daily was recommended for 3-12 months

8. Jeremias et al., Circulation 2008;118:632-8 Methods – Study Endpoints Baseline clinical and procedural data were collected prospectively In-hospital outcomes in patients according to baseline troponin status (elevated vs. normal) were evaluated according to site-specific reference levels All events were adjudicated by 2 observers independently Study endpoints included a composite of death and MI at hospital discharge and at 1 year

9. Jeremias et al., Circulation 2008;118:632-8 Methods – Statistical Analysis A stepwise, sequentially saturated multivariate model was used with adjustments for the following variables: Demographic: Age, gender Clinical: DM, prior MI, prior CABG, estimated GFR Angiographic: No. of diseased vessels, no. of lesions treated, bifurcation lesion, type B2 or C lesion, thrombus Treatment variables: Pre-procedure thienopyridine use

10. Jeremias et al., Circulation 2008;118:632-8 Results - Prevalence of Baseline cTn elevation in Stable CAD Degree of cTn Elevation 1-3x ULN69.7% 3-5x ULN8.5% 5-10x ULN14.1% >10x ULN7.7%

11. Jeremias et al., Circulation 2008;118:632-8 Baseline Clinical Characteristics Troponin +Troponin -p n=142 n=2240 Age, years 65.5±10.8 64.5±10.7 NS Arterial Hypertension 84.4% 78.7%NS Diabetes Mellitus 37.3% 34.6%NS Hyperlipidemia 81.6% 79.0%NS Current Smoking 20.7% 20.5%NS eGFR, ml/min/1.73m 2 81.6±36.7 89.5±44.1 0.017 LV EF<35% 6.3% 7.2%NS Previous MI 20.6% 23.7%NS Previous CABG 23.2% 23.4%NS

12. Jeremias et al., Circulation 2008;118:632-8 Baseline Angiographic Characteristics Troponin +Troponin -p n=212 Lesions n=3063 Lesions Lesions treated, n1.5±0.81.4±0.6NS Type B2/C lesions 58.4% 50.4% 0.01 Angiographic Thrombus 6.1%5.8%NS Pre-procedure TIMI 3 flow 83.0%83.9%NS Bifurcation Lesion15.1%10.4%0.03 DES implanted93.0%92.9%NS Total stent length, mm 23.6±13.4 22.2±12.3NS Min. stent diameter, mm 3.0±0.83.0±0.9NS Glycoprotein IIb/IIIa Inhibitor34.3%25.3%NS Bivalirudin27.1%49.8%<0.001 Clopidogrel Pre-Treatment43.7%58.6%0.002

13. Jeremias et al., Circulation 2008;118:632-8 Results – Death/MI P=0.06 P<0.001 % %

14. Jeremias et al., Circulation 2008;118:632-8 Results – Repeat PCI/CABG P=0.06 P=NS % %

15. Jeremias et al., Circulation 2008;118:632-8 Results – In Hospital Clinical Outcomes Troponin + Troponin - p n=142 n=2240 Death or MI13.4% 5.6% <0.001 Death0.7%0.0% 0.06 MI13.4% 5.6%<0.001 Urgent Repeat PCI1.4%0.2% 0.06 Urgent CABG0.7%0.3% NS Stent Thrombosis0.0%0.2% NS

16. Jeremias et al., Circulation 2008;118:632-8 Risk-Adjusted Risk of in-Hospital Death or MI Univariate analysis Adjusted for demographic and clinical Factors Adjusted for demographic, clinical, angiographic, and treatment factors Adjusted for demographic, clinical and angiographic Factors Adjusted for demographic Factors Odds Ratio 0246

17. Jeremias et al., Circulation 2008;118:632-8 One-Year Clinical Outcomes Troponin +Troponin -Adjusted HR p Death or MI16.8% 7.3% 2.03 (1.2-3.3)0.005 Death2.4%0.4%4.78 (1.2-19.4)0.03 MI15.5%7.0%2.00 (1.2-3.3)0.007

18. Jeremias et al., Circulation 2008;118:632-8 Limitations Registry data not as reliable as prospective, randomized trials Cannot rule out selection bias as PCI strategy and overall medical care was left to the discretion of the operator

19. Jeremias et al., Circulation 2008;118:632-8 Conclusion The prevalence of elevated troponin levels in elective patients (stable angina or positive stress test) undergoing PCI is surprisingly high Baseline troponin elevation is associated with a 2-fold increased risk of death or MI in-hospital and at 1-year follow up If these findings are confirmed in future studies, consideration should be given to routine testing of troponin in this population before PCI If more aggressive pharmacologic or PCI strategies are warranted in this high-risk group to decrease adverse events is currently unknown