Equipoise Does Not Exist for REVIVE IT

1. Equipoise Does Not Exist for REVIVE IT Andrew Boyle, MD Heart and Vascular Center Director, Florida Chairman of Cardiology Medical Director of Heart Failure, Cardiac Transplantation, and Mechanical Circulatory Support Cleveland Clinic Florida Weston, FL

2. Put Another Way: Is this the right time, with the right device, with the right adverse event profile to move forward with REVIVE IT in a less ill population of patients?

3. Relevant Financial Relationship Disclosure Statement Equipoise with REVIVE IT Andrew Boyle, MD I will not discuss off label use and/or investigational use of drugs/devices The following relevant financial relationships exist related to my role in this session: Thoratec: Medical Advisory Board and Honoraria

4. Actuarial Survival vs REMATCH 68% CF LVAD 58% 55% 52% LVAD REMATCH: 23% 25% PF LVAD 24% OMM REMATCH 8% Rose E et al. NEJM 2001; 345:1435-43 Slaughter M et al. NEJM 2009; 361: 1-11.

5. WISL INTERMACS Categories

6. WISL INTERMACS Categories

7. Patient Demographics

8. Survival to D/C Based on INTERMACS Group 3 vs Group 1: p = 0.02 Group 3 vs Group 2: p = 0.59 Group 2 vs Group 1: p < 0.009 Group 1: INTERMACS 1: crash and burn Group 2: INTERMACS 2 and 3: hospitalized and inotrope-dependent Group 3: INTERMACS 4 – 7: poor functional capacity Boyle A, et al. JHLT 2011; 30:402-407.

9. Lengths of Stay Based on INTERMACS Group 3 vs Group 1: p < 0.001 Group 3 vs Group 2: p < 0.001 Group 2 vs Group 1: p = 0.62 Group 1: INTERMACS 1: crash and burn Group 2: INTERMACS 2 and 3: hospitalized and inotrope-dependent Group 3: INTERMACS 4 – 7: poor functional capacity Boyle A, et al. JHLT 2011; 30:402-407.

10. Actuarial Survival on MCS Group 3 vs 1: p = 0.011 Group 3 vs 2: p = 0.065 Group 2 vs 1: p = 0.18 Boyle A, et al. JHLT 2011; 30:402-407.

11. Heartware BTT Secondary Outcome: Survival HVAD Control % Survival p = .39 Event: Death (censored at transplant or recovery) ITT Population Days Post Implant Presented at AHA 2010 by K. Aaronson et al.

13. Have We Truly Shifted to a Less Sick Population?

14. The “LVAD Triad” for Successful Widespread Adoption

15. Adverse Events with Continuous Flow VADs Kirklin J et al. J Heart Lung Transpl 2013; 32: 141 – 156.

16. Heartware Adverse Event Profile Presented by Maltais S et al at ISHLT 2014.

17. Overall Occurrence of Confirmed Pump Thrombosis at 3 Months after HM II Implantation Starling RC et al. N Engl J Med 2014;370:33-40.

18. Occurrence and Incidence of Confirmed Pump Thrombosis Stratified According to Implantation Date. Starling RC et al. N Engl J Med 2014;370:33-40.

19. LVAD Pump Thrombosis

20. ROADMAP: Thoratec Initiated Post-marketing StudyREVIVE-IT: Thoratec Supported NHLBI Trial

21. ROADMAP and REVIVE-ITComplementary Studies Exploring HeartMate II in Earlier-Stage HF 7 6 5 4 3 2 1 INTERMACS Profiles FDA Approval: Class IIIB / IV CMS Coverage: Class IV Growing Acceptance Currently Not Approved Limited Adoption

22. And How Representative are These Patients Anyways? • Anticipating 2500 screening failures in the registry to find 100 eligible patients for the study • How meaningful is that to my clinical practice?

23. Who Are the Patients Who Would Consent to Such a Study? • Have to agree to be randomized to a VAD • Therefore will be a selected population of patients who are already interested in a VAD • Being randomized to OMM arm is not a benign event for these patients: remember patients assigned to the XVE arm of the HM II DT trial?

24. Conclusions • We should be moving to a less sick population which is the ambulatory Class IV patient • Data will be needed to convince MD’s to refer for MCS in IM 4 and 5 patients let alone IM 6 and 7 • The devices currently commercially available do not have a favorable adverse event profile that would justify moving to a Class III population • We will not get a DO OVER. If this is done poorly MCS will forever be banished to the inotrope dependent patient. We better do it right the first time.