Download - HAT Related Disclosures Gust H. Bardy, MD
HAT Related Disclosures Gust H. Bardy, MD
Research grants – United States National Heart Lung and Blood Institute
Research grants – Philips Medical Systems
Research grants – Laerdal Medical Systems
Consultant – Philips
Board membership, equity, intellectual property – Cameron Health
Intellectual property – Medtronic
The Home Automated External Defibrillator Trial (HAT)
April 1, 2008 American College of Cardiology
Chicago, Illinois
HAT Investigative Team Gust H. Bardy: PI – Coordinating Center, Seattle Institute for Cardiac Research
– Jill Anderson, George Johnson, Eric Bischoff, Amanda Brown, Crystal Munkers
Kerry L. Lee: Co-PI Biostatistics – Duke University– Steve McNulty, Meredith Smith, Phillip Smith
Daniel B. Mark: EQOL – Duke University– Nancy Clapp-Channing, Linda Davidson-Ray, Diane Marshall-Liu
Jeanne E. Poole: AED Data Core Lab – University of Washington
Roger D. White: EMS Coordination – Mayo Clinic
Douglas L. Packer: SCA/Death Analysis – Mayo Clinic
W.T. Longstreth, Jr.: Neurological outcomes – University of Washington
Paul Dorian: University of Toronto, Canadian Country PI– Katherin Allen
Warren Smith: Auckland General Hospital, New Zealand Country PI– Julie Yallop
William D. Toff: University of Leicester, United Kingdom Country PI
Andrew M. Tonkin: Monash University, Australia Country PI– Julie J. Yallop
Eleanor B. Schron, Yves Rosenberg, Jerry Fleg, Michael Proschan, Nancy Geller: U.S. National Heart Lung Blood Institute
Erika Friedmann, Sue Thomas: University of Maryland
HAT Funding
U.S.A. National Institutes of Health, Heart, Lung and Blood Institute
Philips Medical
Laerdal MedicalAEDs and supplies
HAT: Background
SCA occurs every 2-3 minutes in the U.S. 50% have no known heart disease 70% occur in the home 50% of home SCA occurs in the bedroom or
adjacent bathroom VF in 90% of SCA Death risk increases 10% per minute of collapse
Expected Survival for OOH-VF
Weaver WD et al. NEJM 2002; 347:1223
0
20
40
60
80
100
1 2-7 8-15
Su
rviv
al (
%)
Estimated Time from Collapse to Defibrillator Shock(minutes)
Cardiac-rehabilitation programs,electrophysiology laboratories
PAD programs
Home, after EMS responseto 911 request
HAT: Population
A balance between sufficient risk and too much risk
ICD population too much risk, ~ 7% per annum
Goal: modest risk, ~4% per annum, sufficient to test the hypothesis within reasonable time and cost.
HAT: Hypothesis
An AED in the home would reduce all-cause mortality above that achieved from a conventional lay response to SCA.
R
HAT Protocol
Anterior MI post-hospitalization, any duration
No cath, EF, echo requirements
+Spouse/Companion
No ICD
-blocker, statin, ACEI, ASA
Made aware of SCD potential
Call EMS 1st
CPR 2ndUse AED 1st
Call 2nd, CPR 3rd
N=7,000
Sample Size/Power Considerations
Predicted control mortality rate: 4% annually (10% at 2.5 years)
Half the deaths projected to be sudden cardiac arrest (SCA)
VF in >90% of SCA
Patients at home with spouse/companion >50% of the time
Loss of spouse/companion <5%
Crossover rate <2%
Use of AED projected to reduce– Death from SCA by 40%– Total mortality by 20%
Alpha = 0.05, Power = 0.90
Target sample size: 7,000 patients
HAT: Therapy
Video based self-instruction – with or without an AED section
appropriate for arm of study
Booklet, internet, phone support
Optional hands-on staff instruction
Yearly follow-up and after events
All data and randomization web-based
AED for Home Use
About the size of a Dostoyevsky novel
Weight 3.3 pounds
Adaptive voice coaching
Activate by pressing Blue “i” Button
Coaches basic assessment, CPR steps
Indicates rate, depth for CPR
Changes rescue instructions according to speed of response of user
i
HAT: Recommended AED Location
Keep in visible location in bedroom or adjacent bathroom.
Visibility allows check for functionality at a glance.
AED not to be moved unless away from home > 1 day.
HAT: Endpoints
Primary All-cause mortality
Secondary Sudden cardiac mortality In-home, witnessed
mortality AED safety and
effectiveness
• First patient enrolled January 23, 2003
• Last patient enrolled October 20, 2005– total = 7001 patients
• Last follow-up September 30, 2007
• Data base locked March 27, 2008
• Randomization at 178 clinical sites in 7 countries
HAT Study Timeline
N = 7001
Number of Patients Enrolled
Patient Demographics and History
Control(N=3506)
AED(N=3495)
Age (yrs) 62.0 (54.0, 70.0) 62.0 (54.0, 70.0)Female 18% (626) 17% (594)Minority 14% (478) 12% (428)Anterior MI
Q-wave 64% (2237) 65% (2272) Non Q-wave 36% (1269) 35% (1222)Years since anterior MI 1.8 (0.4, 5.3) 1.7 (0.4, 5.2)
Patient HistoryControl
(N=3506)AED
(N=3495)
NYHA CHF Class
I 66% (2307) 65% (2263)
II 29% (1016) 30% (1037)
III 5% (174) 6% (193)
IV <1% (9) <1% (2)
LVEF value 45.0 (35.0, 55.0) 45.0(35.0, 55.0)History of CABG 26% (907) 27% (960)Any revascularization 72% (2518) 73% (2537)Diabetes 23% (792) 20% (712)Hypercholesterolemia 80% (2804) 79% (2753)
Baseline Medications
Control(N=3506)
AED(N=3495)
Beta Blocker 80% (2793) 78% (2738)ACEI or ARB 81% (2853) 82% (2866)Statin 90% (3141) 89% (3100)Aspirin or Warfarin 93% 94%Spironolactone 6% 7%Other Diuretic 26% 25%Insulin 7% 6%Oral hypoglycemics 14% 13%
Spouse/Companion Demographics
Control(N=3506)
AED(N=3495)
Relationship to Patient
Spouse 87% (3055) 89% (3095)
Age 58.0 (49.0, 67.0) 58.0 (50.0, 66.0)
Female 82% (2870) 83% (2906)
Spouse/Companion Demographics (cont.)
Control(N=3506)
AED(N=3495)
Employment Status
Full Time 32% (1110) 32% (1113) Part Time 18% (619) 17% (577) Not Employed 51% (1777) 52% (1805)
Estimated hours/day away from home
4.0 (2.0, 7.5) 4.0 (2.0, 8.0)
Completed Secondary School 81% (2851) 81% (2831)
Results
Compliance and Crossovers
Control(N=3506)
AED(N=3495)
Spouse/companion no longer willing, able or available
4.0% (132) 4.8% (167)
Received ICD 4.6% (155) 4.2% (145)
0%
2%
4%
6%
8%
10%
0 6 12 18 24 30 36 42 48
Mo
rtal
ity
Rat
e
Months
Control Group
8.5%
Primary Mortality Endpoint – Control Arm
0%
2%
4%
6%
8%
10%
0 6 12 18 24 30 36 42 48
Mo
rtal
ity
Rat
e
Months
Control Group
AED Group
Primary Mortality Endpoint – Control Arm
Primary Endpoint – Intention to Treat
HR = 0.97, 95% CI = 0.81, 1.17p = 0.77
HR = 0.97, 95% CI = 0.81, 1.17p = 0.77
0%
2%
4%
6%
8%
10%
0 6 12 18 24 30 36 42 48
Mo
rtal
ity
Rat
e
Months
Control Group (228 deaths)
AED Group (222 deaths)
8.5%8.5%7.9%7.9%
HR = 0.97, 95% CI = 0.81, 1.17p = 0.77
HR = 0.97, 95% CI = 0.81, 1.17p = 0.77
100% vital status known
Median follow-up = 37.3 mo
Deaths
Control (N=3506)
AED(N=3495)
Hazard Ratio(95% CI)
Death 228 (6.5%) 222 (6.4%) 0.97 (0.81-1.17)
Cardiac 129 (57%) 138 (62%) 1.07 (0.84-1.36)
Non-cardiac 89 (39%) 81 (36%) 0.91 (0.67-1.23)
Unknown Cause 10 (4%) 3 (1%) --
Cardiac Deaths
Control (N=3506)
AED(N=3495)
Hazard Ratio(95% CI)
Total Cardiac 129 (57%) 138 (62%) 1.07 (0.84-1.36)
Tachyarrhythmia 84 (37%) 85 (38%) 1.01 (0.75-1.37)
Heart Failure 28 (12%) 36 (16%) 1.28 (0.78-2.10)
Non-arrhythmia 16 (7%) 16 (7%) 1.00 (0.50-2.00)
Not Classifiable 1 (0.4%) 1 (0.5%) --
Death from Tachyarrhythmia
Control(N=3506)
AED(N=3495)
Sudden (160 of 169 tachy)
78 82
Onset location:
Home 60 57
Home, witnessed 31 27
Public place/work 5 4
Hospital/care facility 8 10 Other/unknown 5 11
Resuscitated Cardiac Arrest
Control(N=3506)
AED(N=3495)
Total events 19 19
Onset location:
Home 8 8
Home, witnessed 6 7
Public place/work 2 1
Hospital/care facility 6 9 Other/unknown 3 1
Summary of AED Use
3495 AED Patients3495 AED Patients
32 had AED applied32 had AED applied
14 (44%) received shock
14 (44%) received shock
18 (56%) had no shock
18 (56%) had no shock
9 died within 48 hrs
9 died within 48 hrs
5 survived > 48 hrs
5 survived > 48 hrs
1 died 4 days
post-arrest
1 died 4 days
post-arrest
4 alive at end
of study
4 alive at end
of study
Good Samaritan Use of AED
Instances where AED was used for neighbors or visitors
7
No shock advised (all 3 died)
3
Shock advised, VF terminated 4
Discharged from hospital alive 2
AED vs. Control Hazard Ratios - Subgroups
N HR 95% CIAll Patients 7001 0.97 (0.81-1.17)
Gender Female 1220 0.99 (0.66-1.47)Male 5781 0.98 (0.79-1.2)
Age < 65 yrs 4039 0.91 (0.66-1.26)≥ 65 yrs 2962 1.02 (0.82-1.28)
Race Minority 795 0.74 (0.45-1.22)Non-minority 6206 1.02 (0.84-1.25)
Country US 2036 0.92 (0.66-1.28)Canada 1891 0.95 (0.69-1.33)Australia or NZ 2034 1.11 (0.77-1.61)EU 1040 0.89 (0.53-1.51)
0.25 1 4
AED vs. Control Hazard Ratios - Subgroups
N HR 95% CILVEF ≤ 35% 1438 0.99 (0.75-1.32)
> 35% 4187 0.91 (0.68-1.21)Not measured 1376 1.2 (0.76-1.9)
Diabetes No 5497 1.16 (0.92-1.47)Yes 1504 0.77 (0.57-1.05)
NYHA Class I or II 6623 1.01 (0.82-1.24)III or IV 378 0.81 (0.54-1.21)
Prior CABG No 5134 0.92 (0.73-1.16)Yes 1867 1.05 (0.77-1.41)
0.25 1 4
AED vs. Control Hazard Ratios - Subgroups
N HR 95% CISpouse/companionDid not complete1319 0.79 (0.54-1.16)secondary school Completed 5682 1.04 (0.84-1.28)
Employment Full-time 2284 1.01 (0.56-1.81)status Part-time 697 0.89 (0.41-1.92)
Not Employed 4020 1 (0.82-1.23)
Duration of < 120 msec 6214 0.99 (0.79-1.22)QRS interval ≥ 120 msec 724 1.09 (0.74-1.6)
Type of MI Anterior non Q-wave 2491 1.13 (0.85-1.51)Anterior Q-wave 4509 0.88 (0.69-1.12)
0.25 1 4
Conclusions
• HAT evaluated the all-cause mortality benefit of AEDs in the homes of patients with a previous anterior-wall MI who were not otherwise candidates for an ICD.
Conclusions
• HAT evaluated the all-cause mortality benefit of AEDs in the homes of patients with a previous anterior-wall MI who were not otherwise candidates for an ICD.
• Mortality rates over 4 years of follow-up were low, ~half the level expected from prior data.
Conclusions
• HAT evaluated the all-cause mortality benefit of AEDs in the homes of patients with a previous anterior-wall MI who were not otherwise candidates for an ICD.
• Mortality rates over 4 years of follow-up were low, ~half the level expected from prior data.
• AEDS were used without any adverse consequences or inappropriate shocks.
Conclusions
• HAT evaluated the all-cause mortality benefit of AEDs in the homes of patients with a previous anterior-wall MI who were not otherwise candidates for an ICD.
• Mortality rates over 4 years of follow-up were low, ~half the level expected from prior data.
• AEDS were used without any adverse consequences or inappropriate shocks.
• There was no significant reduction in death from any cause with a home AED.
Conclusions
• HAT evaluated the all-cause mortality benefit of AEDs in the homes of patients with a previous anterior-wall MI who were not otherwise candidates for an ICD.
• Mortality rates over 4 years of follow-up were low, ~half the level expected from prior data.
• AEDS were used without any adverse consequences or inappropriate shocks.
• There was no significant reduction in death from any cause with a home AED.
• The very low event rate, the high proportion of unwitnessed events, and the underuse of AEDs in emergencies, rather than a lack of device efficacy, appear to explain these results.