HAT Related Disclosures Gust H. Bardy, MD

1. 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

2. The Home Automated External Defibrillator Trial (HAT) April 1, 2008 American College of Cardiology Chicago, Illinois

3. 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

4. HAT Funding • U.S.A. National Institutes of Health, Heart, Lung and Blood Institute • Philips Medical • Laerdal Medical AEDs and supplies

5. 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

6. Expected Survival for OOH-VF Cardiac-rehabilitation programs, electrophysiology laboratories PAD programs Survival (%) Home, after EMS response to 911 request Estimated Time from Collapse to Defibrillator Shock (minutes) Weaver WD et al. NEJM 2002; 347:1223

7. 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.

8. HAT: Hypothesis • An AED in the home would reduce all-cause mortality above that achieved from a conventional lay response to SCA.

9. HAT Protocol Anterior MI post-hospitalization, any duration No cath, EF, echo requirements +Spouse/Companion No ICD b-blocker, statin, ACEI, ASA Made aware of SCD potential R Call EMS 1st CPR 2nd Use AED 1st Call 2nd, CPR 3rd N=7,000

10. 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

11. 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

12. 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

13. 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.

14. HAT: Endpoints Primary  All-cause mortality Secondary  Sudden cardiac mortality  In-home, witnessed mortality  AED safety and effectiveness

15. HAT Study Timeline • 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

16. N = 7001 Number of Patients Enrolled

17. Patient Demographics and History

18. Patient History

19. Baseline Medications

20. Spouse/Companion Demographics

21. Spouse/Companion Demographics (cont.)

22. Results

23. Compliance and Crossovers

24. Primary Mortality Endpoint – Control Arm 8.5%

25. Primary Mortality Endpoint – Control Arm

26. 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 8.5% 7.9% 100% vital status known Median follow-up = 37.3 mo

27. Deaths

28. Cardiac Deaths

29. Death from Tachyarrhythmia

30. Resuscitated Cardiac Arrest

31. Summary of AED Use 3495 AED Patients 32 had AED applied 14 (44%) received shock 18 (56%) had no shock 9 died within 48 hrs 5 survived > 48 hrs 1 died 4 days post-arrest 4 alive at end of study

32. Good Samaritan Use of AED

33. AED vs. Control Hazard Ratios - Subgroups N HR 95% CI All 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

34. AED vs. Control Hazard Ratios - Subgroups N HR 95% CI LVEF ≤ 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

35. AED vs. Control Hazard Ratios - Subgroups N HR 95% CI Spouse/companion Did not complete 1319 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

36. 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.

37. 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.

38. 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.

39. 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.

40. 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.