equipoise does not exist for revive it

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

Months0 6 12 18 24

Perc

ent S

urvi

val

0102030405060708090

100

CF LVAD 68%

58% 55%

PF LVAD 24%

OMM REMATCH 8%

LVAD REMATCH: 23%

25%

52%

Rose E et al. NEJM 2001; 345:1435-43 Slaughter M et al. NEJM 2009; 361: 1-11.

WISL INTERMACS Categories

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 < 0.009

70.4

93.5 95.8

0

20

40

60

80

100

% s

urvi

val

Group 1(n=27)

Group 2(n=48)

Group 3 (n=24)

Boyle A, et al. JHLT 2011; 30:402-407.

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 < 0.001 Group 3 vs Group 2: p < 0.001 Group 2 vs Group 1: p = 0.62

44 41

17

0

10

20

30

40

50

60

Days

Group 1(n=27)

Group 2(n=48)

Group 3(n=24)

Boyle A, et al. JHLT 2011; 30:402-407.

0

20

40

60

80

100Su

rviv

al (%

)

0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36

Months post-LVAD

Group 1 Group 2 Group 3

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.

60

70

80

90

100

0 60 120 180 240 300 360Days Post Implant

% S

urvi

val

Event: Death (censored at transplant or recovery) ITT Population

Heartware BTT Secondary Outcome: Survival

Days Post Implant Treatment Control

30 98.6% 96.6%

90 95.6% 93.6%

180 93.9% 90.2%

360 90.6% 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;370:33-40.

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

Title Acronym Objective Status

Risk Assessment and Comparative Effectiveness Of Left Ventricular Assist Device and Medical Management in Ambulatory Heart Failure Patients

ROADMAP Compare 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-IT Compare 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

1 2 3

ROADMAP and REVIVE-IT Complementary Studies Exploring HeartMate II in Earlier-Stage HF

4 5 6 7 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.