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 ChairmanDept of Anesthesiology

Duke University Health System

Analysis from the Three Randomized ECLIPSE Trials

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Disclosures

► Abbott (Research Support)

► Baxter (Speaker)

► Medwave (Director)

► Regado Biosciences (Consultant)

► The Medicines Company (Consultant)

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Acknowledgements

Cornelius Dyke, MD Dean Kereiakes, MD

Jerrold H. Levy, MD Philip Lumb, MD

Albert Cheung, MD Howard Corwin, MD

Kevin Stierer, MD Mark Newman, MD

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Background

► Maintaining optimal BP control during cardiac surgery is a significant and common challenge1-5

► 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; 94:1079-844 Estafanous, F. Am J Cardiol, 1980, p685; 5 Landymore, R. Can J Surg, 1980

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Objective

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

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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

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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

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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

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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

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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

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AUC Analysis

Time (hours)

SBP

Lower

Upper

0 6 12 2418

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Baseline Characteristics

PatientsN=1512

Age, median (range) 65 (19-89)

Male 73%

Caucasian 83%

History of HTN 86%

CHF 19%

COPD 14%

Recent MI (< 6 mos) 18%

Prior CABG 4%

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Procedural characteristics

PatientsN=1512

Treatment Clevidipine NTG SNP NIC

49.7%18.4%18.7%12.8%

Surgery duration, median hrs 3.28

Procedure CABG Valve replacement/repair CABG & Valve replacement/repair Other

77.0%13.1%9.7%0.2%

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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

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Logistic Regression Results: Predictors of Mortality

P-Value Odds Ratio

95% CI [Lower Limit, Upper Limit]

Surgery Duration (hour) <0.0001 1.517 [1.240, 1.856]

Age (year) 0.0003 1.070 [1.031, 1.110]

Pre-op Creatinine ≥ 1.2 mg/dL 0.0031 2.670 [1.392, 5.122]

AUC (1mmHg*min) 0.0069 1.003 [1.001, 1.004]

Additional surgical procedures 0.0089 2.409 [1.246, 4.655]

Pre-op Hgb (g/dL) 0.0135 0.824 [0.707, 0.961]

Pre-op SBP >160 or DBP > 105 0.0228 2.386 [1.147, 4.963]

History of COPD 0.0228 2.326 [1.125, 4.812]

History of recent MI (<6 months prior) 0.0312 2.197 [1.073, 4.497]

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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]

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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