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


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


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


• Mortality rates over 4 years of follow-up were low, ~half the level expected from prior data.

Conclusions



• AEDS were used without any adverse consequences or inappropriate shocks.

Conclusions




• There was no significant reduction in death from any cause with a home AED.

Conclusions




• 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.

Documents

HAT Related Disclosures Gust H. Bardy, MD