Transcript Debate Equipoise Exists for a Trail in the Less Ill Heart Failure

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
100
90
Percent Survival
80
68%
70
CF LVAD
60
55%
50
52%
58%
LVAD REMATCH: 23%
40
30
20
25%
PF LVAD 24%
10
OMM REMATCH
0
0
6
Rose E et al. NEJM 2001; 345:1435-43
Slaughter M et al. NEJM 2009; 361: 1-11.
12
Months
18
8%
24
WISL INTERMACS Categories
WISL INTERMACS Categories
Patient Demographics
Survival to D/C Based on INTERMACS
93.5
% survival
100
80
95.8
Group 3 vs Group 1: p = 0.02
70.4
Group 3 vs Group 2: p = 0.59
60
Group 2 vs Group 1: p < 0.009
40
20
0
Group 1
(n=27)
Group 2
(n=48)
Group 3
(n=24)
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.
Lengths of Stay Based on INTERMACS
60
Days
50
44
Group 3 vs Group 1: p < 0.001
41
40
Group 3 vs Group 2: p < 0.001
30
17
20
Group 2 vs Group 1: p = 0.62
10
0
Group 1
(n=27)
Group 2
(n=48)
Group 3
(n=24)
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.
Actuarial Survival
Overall Survival on MCS
100
80
60
40
Group 3 vs 1: p = 0.011
Group 3 vs 2: p = 0.065
Group 2 vs 1: p = 0.18
20
0
0
2
4
6
8 10 12 14 16 18 20 22 24 26 28 30 32 34 36
Months post-LVAD
Group 1
Boyle A, et al. JHLT 2011; 30:402-407.
Group 2
Group 3
Heartware BTT Secondary Outcome: Survival
100
HVAD
% Survival
90
Control
80
70
60
0
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%
60
120
180
p = .39
Event: Death (censored at
transplant or recovery)
ITT Population
240
Days Post Implant
Presented at AHA 2010 by K. Aaronson et al.
300
360
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.
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.
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
ROADMAP and REVIVE-IT
Complementary Studies Exploring HeartMate II in Earlier-Stage HF
NYHA
Class III
INTERMACS Profiles
Class
IIIB
7
6
Class IV
(Ambulatory)
4
5
Class IV
(On Inotropes)
3
2
1
FDA Approval: Class IIIB / IV
CMS Coverage: Class IV
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.