1. TIMI 11BESSENCE Enoxaparin for UA/NQMI: TIMI 11B-ESSENCE Meta-Analysis Antman EM et al, Circulation 1999 Oct 12;100(15):1602-8

2. TIMI 11BESSENCE Objectives of Meta-Analysis 1. Provide a more precise estimate of enoxaparin’s effects on: - death + cardiac ischemic events - major hemorrhage 2. Determine onset and duration of treatment effect with enoxaparin Antman EM et al, Circulation 1999 Oct 12;100(15):1602-8

3. TIMI 11BESSENCE Comparison of Trials : Dose of Study Rx TIMI 11 B ESSENCE TIMI 11 B ESSENCE IV UFH Bolus 70 U/kg 5000 U Infusion 15 U/kg/h 1000 U/h aPTT (x control) 1.5-2.5 1.5-2.5 Med Dur. Rx (d) 3.0 2.6 Enoxaparin (Acute) Bolus 30 mg None S.C. Q 12 h (mg/kg) 1.0 1.0 Med Dur. Rx (d) 4.6 2.6 Enoxaparin (Chronic-43 d) 40 mg (<65 kg) None 60 mg (>65 kg) 60 mg (>65 kg) Antman EM et al, Circulation 1999 Oct 12;100(15):1602-8

4. TIMI 11BESSENCE Comparison of Trials : Patient Characteristics TIMI 11 B ESSENCE (%)(%) TIMI 11 B ESSENCE (%)(%) Age (y)6664 Diabetes Mellitus20%22% Current Smoker27%24% HTN50%54% Prior MI32%46% ECG: ST dev37%29% Normal36%44% Presenting Ilness: Uns Ang59%69% NQMI 34%21% Antman EM et al, Circulation 1999 Oct 12;100(15):1602-8

5. TIMI 11BESSENCE MethodsMethods Prespecified Endpoints Death Death/MI/Urg Revasc Death/MI Major hemorrhage Pooling Procedures : Odds Ratio (95%CI) Peto Method Mantel-Haenszel Method DerSimonian + Laird Method Heterogeneity Testing Antman EM et al, Circulation 1999 Oct 12;100(15):1602-8

6. TIMI 11BESSENCE Enoxaparin for UA/NQMI: TIMI 11B-ESSENCE Meta-Analysis Death/MI/Urgent Revasc Day B B B B OVERALL ESSENCE TIMI 11B 8 8 OR % % p p 0.79 (0.69-0.91) 21 0.001 N N 7081 3910 3171 UFH (%) Enox (%) 13.5 11.0 B B B B OVERALL ESSENCE TIMI 11B 0.5 1 1 2 2 43 0.6 0.7 0.8 0.9 Odds Ratio Enox Better UFH Better 0.80 (0.71-0.91) 20 0.0005 7081 3910 3171 18.8 15.6 Antman EM et al, Circulation 1999 Oct 12;100(15):1602-8

7. TIMI 11BESSENCE TIMI 11B-ESSENCE Meta-Analysis Death/MI/Urgent Revasc Antman EM et al, Circulation 1999 Oct 12;100(15):1602-8

8. TIMI 11BESSENCE Enoxaparin for UA/NQMI: TIMI 11B-ESSENCE Meta-Analysis Death/MI OVERALL ESSENCE TIMI 11B Day 8 8 OR % % p p 0.77 (0.62-0.95) 23 0.02 N N 7081 3910 3171 B B B B UFH (%) Enox (%) 5.3 4.1 OVERALL ESSENCE TIMI 11B 0.5 1 1 2 2 43 0.6 0.7 0.8 0.9 Odds Ratio Enox Better UFH Better 0.82 (0.69-0.97) 18 0.02 7081 3910 3171 B B B B B B 8.6 7.1 Antman EM et al, Circulation 1999 Oct 12;100(15):1602-8

9. TIMI 11BESSENCE TIMI 11B-ESSENCE Meta-Analysis Death/MI Antman EM et al, Circulation 1999 Oct 12;100(15):1602-8

10. TIMI 11BESSENCE Death/MI /Urgent Revasc. 0 1 2 3 4 5 6 7 8 9 081624324048566472 % Pts Hours from Randomization UFH ENOX 5.2 % 4.2 % RRR 18% P=0.21 7.3 % 5.5 % RRR 24% P=0.03 ESSENCE TIMI 11 B Early Rx Phase : TIMI 11 B vs ESSENCE Antman EM et al, Circulation 1999 Oct 12;100(15):1602-8

11. TIMI 11BESSENCE 0.512 OVERALL ESSENCE TIMI 11B UFH (%) Enox (%) O.R. Favors ENOX Favors UFH Heterogeneity: All P=NS 1.0 1.5 Major Hemorrhage (Wgt Adj Rx) 1.2 1.1 1.3 OR (95 CI) P 1.52 (0.86-2.69) NS 0.91 (0.47-1.78) NS 1.23 (0.80-1.89) NS Antman EM et al, Circulation 1999 Oct 12;100(15):1602-8

12. TIMI 11BESSENCE ConclusionsConclusions Efficacy 20% in death and cardiac ischemic events Early onset of benefit (48 hours) Durable treatment effect (43 days) Safety No significant in major hemorrhage (wgt adj Rx) Clinical Implications--New Therapeutic Standard Enoxaparin is antithrombin for acute management of UA/NQMI Antman EM et al, Circulation 1999 Oct 12;100(15):1602-8