Docstoc

Blood Pressure Control is an Independent Clinical Trial Results

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

► Abbott (Research Support)

► Baxter (Speaker)

► Medwave (Director)

► Regado Biosciences (Consultant)

► The Medicines Company (Consultant)




                                       2
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




                                             3
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; 94:1079-84
                                 4 Estafanous, F. Am J Cardiol, 1980, p685;
                                 5 Landymore, R. Can J Surg, 1980

                                                                               4
Objective

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




                                                           5
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




                                                              6
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



                                                                 7
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



                                                     8
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

                                                             9
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




                                                              10
AUC Analysis

SBP

Upper




Lower




        0      6       12         18   24
                   Time (hours)

                                            11
Baseline Characteristics
                           Patients
                           N=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%



                                        12
Procedural characteristics
                                     Patients
                                     N=1512
Treatment
   Clevidipine                        49.7%
   NTG                                18.4%
   SNP                                18.7%
   NIC                                12.8%
Surgery duration, median hrs           3.28
Procedure
   CABG                               77.0%
   Valve replacement/repair           13.1%
   CABG & Valve replacement/repair     9.7%
   Other                               0.2%


                                                13
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

                                                         14
Logistic Regression Results:
Predictors of Mortality
                                           Odds      95% CI
                                 P-Value            [Lower Limit,
                                           Ratio     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
                                  0.0312   2.197   [1.073, 4.497]
(<6 months prior)

                                                                    15
 30-Day Mortality by Magnitude of AUC

                              Odds     95% CI
                                      [Lower Limit,
                              Ratio    Upper Limit]


I mmHg x 60 min               1.20    [1.06, 1.27]

2 mmHg x 60 min               1.43    [1.13, 1.61]

3 mmHg x 60 min               1.71    [1.20, 2.05]

4 mmHg x 60 min               2.05    [1.27, 2.61]

5 mmHg x 60 min               2.46    [1.35, 3.31]

           0      1   2   3    4



                                                      16
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




                                                            17

				
DOCUMENT INFO