Sadanandan S. et al. JACC 2004;44:799-803

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. Background • 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

3. Background • 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

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

6. Methods: Study Population • 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

7. Methods: Study Population • 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

8. Results: Study population • 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)

9. Clinical characteristics of the study groups Characteristics No CABG CABG p-value (N=1857) (N=362) Age (mean years) 61 + 12 63 + 10 0.004 Males (%) 64 74 0.001 Caucasian (%) 77 80 0.3 Hypertension (%) 66 67 0.6 DM (%) 27 33 0.02 Hyperlipidemia (%) 60 63 0.3 Current Smoker (%) 28 27 0.7 Family h/o CAD (%) 43 40 0.3 Prior MI (%) 33 29 0.004 Prior PTCA (%) 28 18 0.0001 Prior CABG (%) 24 10 0.0001 H/o Angina (%) 12 17 0.02 CHF (%) 7 7 0.9 Prior ASA (%) 66 67 0.9 H/o CVA (%) 5.8 4.4 0.3 H/o PAD (%) 7.1 10 0.08 ST Deviation  0.5 mm 36 52 <0.0001 Positive Troponin (%) 55 84 <0.0001

10. Variables independently associated with CABG – TACTICS TIMI 18 Sadanandan S. et al. JACC 2004;44:799-803

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

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

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

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

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

16. Conclusions • 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 Sadanandan S. et al. JACC 2004;44:799-803