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

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?

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

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

WISL INTERMACS Categories

Patient Demographics

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 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 < Boyle A, et al. JHLT 2011; 30:

Lengths of Stay Based on INTERMACS 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 Group 3 vs Group 1: p < Group 3 vs Group 2: p < Group 2 vs Group 1: p = 0.62 Boyle A, et al. JHLT 2011; 30:

Actuarial Survival on MCS Group 3 vs 1: p = Group 3 vs 2: p = Group 2 vs 1: p = 0.18 Boyle A, et al. JHLT 2011; 30:

Days Post Implant % Survival Event: Death (censored at transplant or recovery) ITT Population Heartware BTT Secondary Outcome: Survival Days Post Implant TreatmentControl %96.6% %93.6% %90.2% %85.7% p =.39 HVAD Control Presented at AHA 2010 by K. Aaronson et al.

Have We Truly Shifted to a Less Sick Population?

The “LVAD Triad” for Successful Widespread Adoption

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

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

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

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

LVAD Pump Thrombosis

ROADMAP: Thoratec Initiated Post-marketing Study REVIVE-IT: Thoratec Supported NHLBI Trial TitleAcronymObjectiveStatus Risk Assessment and Comparative Effectiveness Of Left Ventricular Assist Device and Medical Management in Ambulatory Heart Failure Patients ROADMAPCompare the effectiveness of HM II versus optimal medical management (OMM) in ambulatory non-inotrope dependent NYHA Class IIIB / IV patients Enrolled 200/200 pts 37 sites) Randomized Evaluation of LVAD Intervention Before Inotropic Therapy REVIVE-ITCompare the effectiveness of HeartMate II versus OMM in NYHA Class III patients with illness not severe enough to qualify for transplant or permanent LVAD therapy based on current guidelines Enrolled 0/100 pts (randomized study) 0/2500 pts (screening registry) 0/14 sites

ROADMAP and REVIVE-IT Complementary Studies Exploring HeartMate II in Earlier-Stage HF INTERMACS Profiles CMS Coverage: Class IV FDA Approval: Class IIIB / IV NYHA Class III Class IIIB Class IV (Ambulatory) Class IV (On Inotropes) Currently Not Approved Limited Adoption Growing Acceptance

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?

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?

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.