1. A Risk Score for Predicting Coronary Artery Bypass Surgery in Patients with Non-ST Elevation Acute Coronary Syndromes Sai Sadanandan, MD*; Christopher P. Cannon, MD**; C. Michael Gibson**; Rajen Desai, MD*; Sabina A. Murphy**, MPH; Peter M. DiBattiste, MD***; Eugene Braunwald, MD** for the TACTICS TIMI-18 Investigators Sadanandan S. et al. JACC 2004;44:799-803

2. Early combination anti-platelet therapy with aspirin and clopidogrel is recommended for patients with non-ST elevation acute coronary syndromes (ACS) The benefits of combination therapy are apparent within the first 24 hours with a 300mg loading dose of clopidogrel However, use of Clopidogrel increases the risk of major bleeding in patients undergoing early CABG Available data indicate that 15-25% of patients with non-STE ACS will require CABG following coronary angiography Background

3. Withholding clopidogrel for at least 5 days prior to CABG reduces the risk of peri-operative bleeding Such a strategy may impose logistic problems in terms of prolongation of hospital stay or may impose increased bleeding risks in pts where early CABG is clinically warranted Ability to estimate the likelihood for in-hospital CABG using readily available admission clinical parameters will be useful This may permit withholding clopidogrel until an early angiogram (< 24 hours) to define the coronary anatomy or anticipate CABG and plan withholding Clopidogrel for at least 5 days prior to CABG Background

4. Objective To develop a simple clinical risk score based on admission clinical variables to estimate the likelihood of in-hospital CABG in patients with UA/NSTEMI enrolled in the TACTICS TIMI-18 trial and To validate the risk score using UA/NSTEMI patient population from the TIMI 11B and TIMI 3B trials

5. TACTICS-TIMI 18 Study Design UA/ NSTEMI Early Invasive Early Conservative PCI/ CABG Cath/ PCI/ CABG Medical Rx Endpoints 6 mos Randomize -24 hrs Chest pain 4- 48 108 hrs hrs ASA, Hep, Tirofiban Angio Hour 0 ETT +ischemia BaselineTroponin Cannon CP et al. Am J Cardiol 1998;82:731-6.

6. We evaluated 2220 pts with UA/NSTEMI randomized to the early invasive strategy or conservative strategy in the TACTICS-TIMI 18 study Patients who underwent CABG following randomization during initial hospitalization were identified and compared to patients who did not undergo CABG Patients with history of prior CABG (N=484) were significantly less likely to undergo in-hospital CABG (OR 0.34, p<0.0001) and were excluded Methods: Study Population

7. Clinical characteristics of patients who underwent in-hospital CABG were compared with patients who did not undergo CABG A logistic regression model was developed to identify clinical variables independently associated with in-hospital CABG A p-value of <0.05 was required for retention in the model A risk score was generated by assigning numerical scores for each variable independently associated with in-hospital CABG Methods: Study Population

8. 2220 pts enrolled in the trial Of these 362 (16.3%) underwent CABG during index hospitalization 22% of Invasive Group and 15% of Conservative Group underwent CABG The median time to CABG: Overall population - 3.8 days (2.5, 6.0) Invasive Group - 3.4 days (1.9, 4.9) Conservative Group - 5.0 days (3.7, 7.9) Results: Study population

9. Characteristics No CABGCABG p-value (N=1857)(N=362) (N=1857)(N=362) Age (mean years) 61 + 1263 + 10 0.004 Males (%) 6474 0.001 Caucasian (%) 7780 0.3 Hypertension (%) 6667 0.6 DM (%) 2733 0.02 Hyperlipidemia (%) 6063 0.3 Current Smoker(%) 2827 0.7 Family h/o CAD (%) 4340 0.3 Prior MI (%) 3329 0.004 Prior PTCA (%) 2818 0.0001 Prior CABG (%) 2410 0.0001 H/o Angina (%) 1217 0.02 CHF (%) 77 0.9 Prior ASA (%) 6667 0.9 H/o CVA (%) 5.84.4 0.3 H/o PAD (%) 7.110 0.08 ST Deviation  0.5 mm 3652 <0.0001 Positive Troponin (%) 5584 <0.0001 Clinical characteristics of the study groups

10. Variables independently associated with CABG – TACTICS TIMI 18 VariableOdds Ratio95% CIP-valueRisk score Hx prior CABG0.350.2-0.5<0.0001-2 (+) Troponins3.92.7 – 5.5<0.00013 Prior Angina1.81.3 – 2.60.0011 ST deviation1.71.3 – 2.2<0.00011 Male Gender1.61.2 – 2.20.0011 Hx PAD1.61.1 – 2.60.0381 Sadanandan S. et al. JACC 2004;44:799-803

11. Distribution of CABG Risk Score - TACTICS TIMI-18 Frequency (%) N=1828 Risk score <3 - 42% 3-5 - 55% >5 - 3% Sadanandan S. et al. JACC 2004;44:799-803

12. Rates of in-hospital CABG by Increasing Risk Score – TACTICS TIMI 18 CABG (%) N=1828 P<0.0001 C-statistic 0.72 Risk score (41 / 763)(221 / 1010)(30 / 55) (n) Sadanandan S. et al. JACC 2004;44:799-803

13. Rates of in-hospital CABG by Increasing Risk Score – TACTICS TIMI 18 CABG (%) N=1828 Inv. P<0.0001 C= 0.71 Cons. P<0.0001 C= 0.73 Risk score Sadanandan S. et al. JACC 2004;44:799-803

14. Validation of association between CABG and Increasing Risk Score – TIMI 11B Trial CABG (%) N=3,722 P<0.0001 C-statistic 0.61 Risk score (76 / 1700) (130 / 1692)(38 / 330) (n) Sadanandan S. et al. JACC 2004;44:799-803

15. Validation of CABG Risk Score – TIMI III Registry CABG (%) N=1,139 P<0.0001 C-statistic 0.66 Risk score (48 / 1078)(121 / 1628)(57 / 523) (n) Sadanandan S. et al. JACC 2004;44:799-803

16. In patients with UA/NSTEMI, a simple risk score based on admission clinical variables estimates the likelihood of in- hospital CABG A risk score of >5 is associated with high likelihood of CABG during index hospitalization The association between increasing risk score and likelihood of CABG was validated in UA/NSTEMI pt population from TIMI 3Registry and TIMI 11B trials and remained significant This score may be helpful in timing of clopidgrel therapy for UA/NSTEMI patients Conclusions Sadanandan S. et al. JACC 2004;44:799-803