1. Blood Pressure Control is an Independent Predictor of Short-term Mortality in Cardiac Surgery Patients: Solomon Aronson, M.D. FACC,FCCP,FAHA,FASE Professor and Executive Vice Chairman Dept of Anesthesiology Duke University Health System Analysis from the Three Randomized ECLIPSE Trials

2. 2 Disclosures ► Abbott (Research Support) ► Baxter (Speaker) ► Medwave (Director) ► Regado Biosciences (Consultant) ► The Medicines Company (Consultant)

3. 3 Acknowledgements Cornelius Dyke, MDDean Kereiakes, MD Jerrold H. Levy, MDPhilip Lumb, MD Albert Cheung, MDHoward Corwin, MD Kevin Stierer, MDMark Newman, MD

4. 4 Background ► Maintaining optimal BP control during cardiac surgery is a significant and common challenge 1-5 ► No studies to-date have shown an association between targeted peri-operative blood pressure control and mortality ► This relationship was examined as part of the ECLIPSE safety program 1 Aronson, S. Circulation 115,733-42,2007 2 Cheung, A. J Card Surg, 2006, S8 3 Aronson, S. Anesth Analg 2002; 94:1079-84 4 Estafanous, F. Am J Cardiol, 1980, p685; 5 Landymore, R. Can J Surg, 1980

5. 5 Objective ► To examine the relationship of targeted peri-operative BP control to mortality

6. 6 Setting ► ECLIPSE, a phase III safety program required for FDA registration of Clevidipine  1512 randomized cardiac surgery pts  Comparators: Nitroglycerin (NTG), Sodium nitroprusside (SNP), Nicardipine (NIC) ► BP measurements were captured over 24 hours  Frequency: Q5 min (pre-/intra-op), Q15 min (post-op) up to 4h and Q60 min after 4h

7. 7 Treatment ► Clevidipine  Initiated 2 mg/hr  Titrated doubling increments Q 90s to 16 mg/hr  40 mg/hr maximum ► Comparators (NTG, SNP, NIC) admin per institutional practice ► Treatment duration up to discharge from the ICU ► Concomitant anti-hypertensives discouraged

8. 8 Inclusion Criteria Pre-randomization ► ≥ 18 years of age ► Written informed consent ► Planned CABG, OPCAB, MIDCAB surgery and/or valve repair/replacement surgery Post-randomization ► Require treatment for peri-operative HTN

9. 9 Exclusion Criteria ► Women of child bearing potential ► CVA ≤ 3 months of randomization ► Intolerance to calcium channel blockers ► Hypersensitivity to NTG, SNP or NIC ► Allergy to the lipid vehicle ► Permanent ventricular pacing ► Any disease/condition that would put the patient at risk ► Participation in another trial within 30 days

10. 10 Statistical Analysis ► Data pooled for 1512 patients ► A multiple logistic regression analysis was performed to determine the association of BP control with 30-day mortality ► BP control was expressed as the cumulative area under the curve (AUC) outside specified SBP ranges ► AUC was analyzed as a continuous variable

11. 11 AUC Analysis Time (hours) SBP Lower Upper 06122418

12. 12 Baseline Characteristics Patients N=1512 Age, median (range)65 (19-89) Male73% Caucasian83% History of HTN86% CHF19% COPD14% Recent MI (< 6 mos)18% Prior CABG4%

13. 13 Procedural characteristics Patients N=1512 Treatment Clevidipine NTG SNP NIC 49.7% 18.4% 18.7% 12.8% Surgery duration, median hrs3.28 Procedure CABG Valve replacement/repair CABG & Valve replacement/repair Other 77.0% 13.1% 9.7% 0.2%

14. 14 Logistic Regression Model Selection ► Candidate variables included:  Demographics  Baseline characteristics  Medical history  Treatment group  AUC  Procedural characteristics p<0.05 required for inclusion in final output

15. 15 Logistic Regression Results: Predictors of Mortality P-Value Odds Ratio 95% CI [Lower Limit, Upper Limit] Surgery Duration (hour)<0.00011.517[1.240, 1.856] Age (year)0.00031.070[1.031, 1.110] Pre-op Creatinine ≥ 1.2 mg/dL0.00312.670[1.392, 5.122] AUC (1mmHg*min)0.00691.003[1.001, 1.004] Additional surgical procedures0.00892.409[1.246, 4.655] Pre-op Hgb (g/dL)0.01350.824[0.707, 0.961] Pre-op SBP >160 or DBP > 1050.02282.386[1.147, 4.963] History of COPD0.02282.326[1.125, 4.812] History of recent MI (<6 months prior) 0.03122.197[1.073, 4.497]

16. 16 I mmHg x 60 min 2 mmHg x 60 min 3 mmHg x 60 min 4 mmHg x 60 min 5 mmHg x 60 min 30-Day Mortality by Magnitude of AUC Odds Ratio 95% CI [Lower Limit, Upper Limit] 1.20[1.06, 1.27] 1.43[1.13, 1.61] 1.71[1.20, 2.05] 2.05[1.27, 2.61] 2.46[1.35, 3.31]

17. 17 Conclusions ► Excursions outside a targeted BP range are correlated with 30-day mortality ► This relationship is direct and proportionate to the magnitude of excursions outside the BP range ► These data suggest that great attention should be given to precise peri-operative BP control ► Future analysis of this finding is warranted