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Current TAVR technologies Update on recent clinical trials
SCAI at SOLACI SOLACI-SOCIME August 7th 2015 Mexico City, DF
Ted Feldman, M.D., MSCAI FACC FESC
Evanston Hospital
Disclosure Information
The following relationships exist:
Grant support: Abbott, BSC, Edwards, WL Gore Consultant: Abbott, BSC, Coherex, Edwards, JenaValve,
Diiachi Sankyo-Lilly, WL Gore
Off label use of products and investigational devices will be discussed in this presentation
Ted Feldman MD, MSCAI FACC FESC
Edwards Lifesciences
SAPIEN XT
Medtronic CoreValve
ACC 2015
No. at Risk
Transcatheter 391 378 354 334 219
Surgical 359 343 304 282 191
18.9%
14.1%
Δ = 4.8
All-Cause Mortality
Months Post-Procedure
4
Δ = 6.5
22.2%
28.6%
Log-rank P=0.04
ACC 2015 All Stroke
5
Edwards Lifesciences
S3
Medtronic CoreValve
Evolut R
Newly Approved in the US
CoreValve Evolut R EnVeo R Delivery System
• 14 F inline sheath
• Outflow shortened and redesigned
• More consistent radial force across annulus range
• Extended skirt at inflow, less traumatic
inflow edge
• Repositionable
18FR
18FR Cook Sheath
18FR
EnVeo R
w/ InLine Sheath
~22 FR (OD) 14FR Equivalent
~4 FR Reduction
Large top-row cells
facilitate coronary
access
Edwards SAPIEN 3
Transcatheter Heart Valve
Sealing Skirt
Balloon-expandable Cobalt Chromium
Frame
20, 23, 26 and 29 mm sizes e14- 16F Sheath
6.3%
5.2%
3.7% 4.5%
3.5%
2.2% 1.6%
1.1% 1.1%
0%
5%
10%
15%
20%
P1B (TF) P1A (All) P1A (TF) P2B (TF) P2B XT (TF) S3HR (All) S3HR (TF) S3i (All) S3i (TF)
All-Cause Mortality at 30 Days Edwards SAPIEN Valves (As Treated Patients)
175 344 240 271 282 583 491 1072 947
SAPIEN SXT SAPIEN 3
PARTNER I and II Trials
Overall and TF Patients
All Strokes at 30 Days Edwards SAPIEN Valves
6.7%
5.6%
4.1% 4.3%
1.5%
2.6%
0%
5%
10%
15%
20%
P1B (TF) P1A (Overall) P2B (TF) P2B XT (TF) S3HR (Overall) S3i (Overall)
179 344 276 284 583 1076
SAPIEN SAPIEN XT SAPIEN 3
PARTNER I and II Trials
Neurologist evaluations (pre- and post)
Next Generation Valves
• Centera • Sapien 3 • CoreValve Evolut R • Jena Valve • Lotus • Venus Aortic Valve • Engager TA • Direct Flow • Trinity • Portico
• Symetis • Colibri • Inovare • Thubikar • Valve Medical • Hydra • TRISKELE • NVT Allegra Valve • MyVal • HLT • TRINITY TA
TAVR Systems with CE-Approval (2007-15)
In Trials…
Edwards Self Expanding CENTERA
• Compatible with14F eSheath
• Deployment achieved via user-controlled motorized handle
• Quick preparation system
• Flex mechanism for optimal coaxial alignment
Distal flex
Touch
deployment
The Edwards CENTERA System is an investigational device only and not for commercial sale
• Double-ring design
• Minimizes risk of PVL
• Repositionable
• Fully retrievable
• 18Fr delivery
• Fully competent during positioning
• No rapid pacing or post-dilatation
• 912 patient trial planned in US
• Randomized 2:1 vs CoreValve
leaflets
DIRECT FLOW Valve Bovine pericardial
SALUS Trial: TranScatheter Aortic Valve RepLacement System Pivotal Trial The Safety and Effectiveness of the Direct Flow Medical
Tanscatheter Aortic Valve System NCT02163850
Bovine Pericardium
Locking Mechanism
Adaptive Seal
Braided Nitinol Frame
Central Radiopaque Positioning Marker
Lotus Valve System
Feasibility Study; Acute Safety & Performance (Extreme/High Risk) N=11; single arm; 23mm valve size
Primary Endpoint: Device success (VARC-1) without MACCE Meredith et al, EuroIntervention 2014; 9(11): 1264-70
Safety & Performance Study (Extreme/High Risk) N=130; single arm; 23 & 27mm valve sizes
Primary Safety Endpoint: All-cause mortality at 30d Enrollment Complete
FDA Approval Study; Safety & Efficacy (Extreme/High Risk) N=1032; Global RCT vs. CoreValve; 23, 25 & 27mm valve sizes
Enrolling
REPRISE I
REPRISE II
REPRISE II Extension
RESPOND
CE Mark Study; Safety & Performance (Extreme/High Risk) N=120; single arm; 23 & 27mm valve sizes
Primary Device Performance Endpoint: Mean pressure gradient at 30d Meredith et al, JACC 2014
REPRISE III
Post Market Safety & Performance Study (Real World) N=1000; single arm; 23, 25 & 27mm valve sizes
Primary Endpoint: All-cause mortality at 30d & 1y Enrolling
Lotus Clinical Program
Comorbidities & Baseline Scores
Age (Years) 84.0 ± 5.2 (250) NYHA Class III or IV 77.2% (193)
Gender (Female) 52.4% (131) euroSCORE 2011 (%) 6.4 ± 6.2 (250)
Diabetes, treated 24.0% (60) STS Score (v 2.73; %) 6.5 ± 4.2 (250)
Atrial fibrillation 37.2% (93) STS Plus Score (%) 10.6 ± 7.7 (250)
Echocardiographic Measurements*
AVA (cm2) 0.7 ± 0.2 (197) LVEF (%) 53.1 ± 10.5 (126)
MR (mod/severe) 10.6% (24) Mean gradient (mmHg) 45.2 ± 13.6 (212)
AR (mod/severe) 13.3% (29) Peak gradient (mmHg) 74.7 ± 21.1 (212)
Frailty Indices Threshold 5 Meter gait speed (sec) 8.6 ± 5.2 (236) > 6
Max grip strength average (kg) 21.1 ± 11.5 (246) ≤ 18
Katz Index 5.7 ± 0.8 (247) < 6
Mini-Cognitive Assessment for Dementia 3.5 ± 1.4 (244) < 4 * Independent Core Lab assessment
Baseline Characteristics REPRISE II with Extended Cohort (N=250)
I Meredith, London Valves 2014
Lotus is an investigational device and not for sale in the US. CE mark received 2013. Information for the Lotus Valve System is for use in countries with applicable product registrations. Indications, contraindications, warnings and instructions for use can be found in the product labeling supplied with each device.
SH-148709-AI FEB2015 Page 20
3.5 5.1 3.3
8.4
4.5 4.2
19 18.6
10.9
15.9
13.4
6.7
0
5
10
15
20
25
301-year Mortality 30-day Mortality
30-Day and 12-Month Mortality in Perspective
SAPIEN XT PARTNER II1
SAPIEN PARTNER II1
CoreValve High Risk2
CoreValve Ext Risk3
CoreValve ADVANCE4
LOTUS REPRISE II5
STS Score: 10.3 11 7.3 10.3 5.3 7.1
N: 284 276 390 489 1015 120
% o
f Pa
tien
ts
1Leon M, ACC 2013., 2Adams D, N Engl J Med 2014., 3Popma J, JACC 2014., 4Linke A, PCR 2014., 5Meredith I et al, J Am Coll Cardiol 2014;64:1339–48 (30 day), Ian Meredith, TCT 2014 (1 year). Results from different studies not directly comparable. Information provided for educational purpose only.
Lotus is an investigational device and not for sale in the US. CE mark received 2013. Information for the Lotus Valve System is for use in countries with applicable product registrations. Indications, contraindications, warnings and instructions for use can be found in the product labeling supplied with each device.
SH-148709-AI FEB2015 Page 21
Major/Disabling Stroke at 30 Days REPRISE II & Other TAVR Studies
3.2 3.0
3.8
5.0
1.2
2.3
3.9
1.7
0
2
4
6
8
Even
t R
ate
(%)
1PARTNER II Inop: Martin Leon, MD at ACC 2013; 2PARTNER A: Smith, et al. N Engl J Med 2011;364:2187; 3PARTNER B: Leon, et al. N Engl J Med 2014; 370: 1790-98; 4CoreValve ADVANCE: Linke A, EuroPCR 2014., 5CoreValve Extreme Risk: Popma J, JACC 2014; 63(19): 1972-81., 6Adams D, N Engl J Med 2014.,7REPRISE II: Meredith I et al, J Am Coll Cardiol 2014;64:1339–48. Results from different studies not directly comparable. Information provided for educational purpose only.
SAPIEN XT PARTNER II Inoperable1
SAPIEN PARTNER II Inoperable1
SAPIEN PARTNER
A2
SAPIEN PARTNER
B3
CoreValve ADVANCE4
CoreValve Ext Risk5
CoreValve High Risk6
LOTUS REPRISE II7
Lotus is an investigational device and not for sale in the US. CE mark received 2013. Information for the Lotus Valve System is for use in countries with applicable product registrations. Indications, contraindications, warnings and instructions for use can be found in the product labeling supplied with each device.
SH-148709-AI FEB2015 Page 22
Valve in Valve Deployments TAVR Clinical Trials and Registries
1.1 0.8
3.7
2.5
1.1 1.4
2.9
4.0
2.9
5.8
3.5 3.9
0.0 0
5
% V
alve
in V
alve
Dep
loym
ent
PAR
TNER
II 4
CH
OIC
E1
PAR
TNER
II 4
PAR
TNER
I (A
and
B) 8
SOU
RC
E9
FRA
NC
E 25
TVT R
egistry6
AD
VA
NC
E2
Co
reValve
Extreme R
isk7
CH
OIC
E1
FRA
NC
E 25
Portico
CE
Trial 3
REP
RISE
II & EX
T1
0
284 121 276 2554 2307 2107 7710 996 489 120 1043 103 250
Results from different studies not directly comparable. Information provided for educational purpose only. 1 Abdel-Wahab, JAMA 2014. , 2Linke, et al. EuroPCR 2014., 3Manoharan, Presented at TCT 2014. 4Leon, et al., ACC 2013. 5Gilard, et al. NEJM 2012. 6Mack, et al. JAMA 2013. 7Reardon, et al. J Thor and Cardiovasc Surgery 2014. 8Makkar, et al. JACC 2013., 9Thomas, et al. TCT 2012. 10Ian Meredith, London Valves 2014.
N:
CoreValve SAPIEN XT SAPIEN LOTUS Portico
Moderate PVL 30 days
11.5
16.9
24.2
9
4.1
18.3
3.4
0
5
10
15
20
25
30
CoreValveExt Risk
PARTNER 2BSAPIEN
PARTNER 2BXT
CoreValve HiRisk
CHOICE XT CHOICECoreValve
SAPIEN 3
Pe
rce
nt
24.2
16.9
14.2
11.5 9.0
4.0 3.4 1.7
0.6 0
5
10
15
20
25
30
% P
atie
nts
wit
h M
od
/Sev
ere
PV
L
SAPIEN XT
PARTNER II, Inop1
SAPIEN PARTNER II Inop1
CoreValve ADVANCE2
CoreValve Extreme
Risk3
CoreValve High Risk4
Portico
CE Study5
SAPIEN 36
Direct Flow
DISCOVER7
LOTUS REPRISE II & EXT8
N=236 N=225 N=639 N=418 N=390 N=75 N=150 N=100 N=250
1Leon M, ACC 2013, 2Linke A, PCR 2014. 3Popma J, JACC 2014; 63(19): 1972-81, 4Adams D, N Engl J Med 2014; 370: 1790-98 5Manoharan, et al. TCT 2014. 6Webb J, EuroPCR 2014. 7Schofer, JACC 2013. 8Meredith I, London Valves 2014
1 Month Moderate & Severe PVL Echo Core Lab Adjudicated Clinical Trials
Lotus is an investigational device and not for sale in the US. CE mark received 2013. Information for the Lotus Valve System is for use in countries with applicable product registrations. Indications, contraindications, warnings and instructions for use can be found in the product labeling supplied with each device.
SH-148709-AI FEB2015 Page 25
Aortic Regurgitation REPRISE I at 2 Years
None
Trivial
Moderate
Discharge 2 Years
No Moderate / Severe AR by Independent Adjudication
Mild
Severe
20
40
60
80
100
0
% o
f Pa
tien
ts
Paravalvular Central Paravalvular Central
n=8 n=9
n=8
n=10
n=1
n=1
n=2 n=1
n=1 n=3
Ian Meredith, TCT 2014.
26
Paravalvular Aortic Regurgitation 250-Patient Interim Analysis
Perc
ent
of
Eval
uab
le
Ech
oca
rdio
gram
s
Paravalvular AR at Baseline
Baseline (N=243)
Discharge (N=244)
None
Trace
Mild
Moderate
Severe
22.2
84.4 35.8
11.1
34.6
4.5
0
20
40
60
80
100
Core-lab Adjudicated Data
3.7 0.8
Repositioning to Resolve PVL
1st Position Reposition
Pacemaker Implantation REPRISE II with Extended Cohort (N=250)
Variable Patients
Newly implanted pacemaker 28.9% (72/249)
Baseline RBBB 27.8% (20/72)
New conduction disturbance post valvuloplasty 34.7% (25/72)
LVOT overstretch ≥10% 61.1% (44/72)
Annulus overstretch ≥10% 34.7% (25/72)
Indication Indication
3rd deg. AV block 59 LBBB & 1st deg. AV block 3
Atrial fibrillation & bradycardia 4 LBBB & 2nd deg. AV block (Type 1) 1
Trifascicular block 1 LBBB, EP study showing severe infranodal disease
3 New LBBB, symptomatic bradycardia 1
Patients Patients
I Meredith, London Valves 2014
Feasibility Study; Acute Safety & Performance (Extreme/High Risk) N=11; single arm; 23mm valve size
Primary Endpoint: Device success (VARC-1) without MACCE Meredith et al, EuroIntervention 2014; 9(11): 1264-70
Safety & Performance Study (Extreme/High Risk) N=130; single arm; 23 & 27mm valve sizes
Primary Safety Endpoint: All-cause mortality at 30d Enrollment Complete
FDA Approval Study; Safety & Efficacy (Extreme/High Risk) N=1032; Global RCT vs. CoreValve; 23, 25 & 27mm valve sizes
Enrolling
REPRISE I
REPRISE II
REPRISE II Extension
RESPOND
CE Mark Study; Safety & Performance (Extreme/High Risk) N=120; single arm; 23 & 27mm valve sizes
Primary Device Performance Endpoint: Mean pressure gradient at 30d Meredith et al, JACC 2014
REPRISE III
Post Market Safety & Performance Study (Real World) N=1000; single arm; 23, 25 & 27mm valve sizes
Primary Endpoint: All-cause mortality at 30d & 1y Enrolling
Lotus Clinical Program
To evaluate the safety and effectiveness of the Lotus™ Valve System
for TAVR in symptomatic subjects with calcific, severe native aortic
valve stenosis who are considered at extreme or high risk for
surgical valve replacement
Lotus Valve CoreValve 23, 25, 27 mm sizes 26, 29, 31 mm sizes
Objective
Study Design
Study Devices
N=1032; Global, prospective, multicenter, controlled trial. 2:1 randomized vs. CoreValve.
Follow up at discharge or 7d, 30d, 6m, 1y annually through 5Y 20 mm < Aortic Annulus Size < 27 mm
REpositionable Percutaneous Replacement of Stenotic Aortic Valve through Implantation of Lotus™ Valve System – Randomized Clinical Evaluation
REPRISE III Trial
Up to 60 Centers United States, Canada, Western Europe and Australia
Study Sites
1st REPRISE III Patient September 22, 2014
Feasibility (Acute Safety, High Risk) N=11; single arm; 23mm valve size
1⁰ Endpoint: Device success (VARC) without MACCE REPRISE I 2-yr f/u
TCT 2014
Post Market Study (Safety & Performance, All Comers) N=1000; single arm; 23, 25 & 27mm valve sizes
1⁰ Safety Endpoint: Mortality at 30 days & 1 year RESPOND
Enrolling: >500 pts
FDA Trial Approval (Safety & Effectiveness, High Risk & Inoperable) N=1032; Lotus (23, 25, 27mm) vs. CoreValve (26, 29, 31mm)
1⁰ Safety Endpoint – 30 days Mortality, stroke, LT/major bleed, AKIN stage 2/3 or major vasc comp
1⁰ Effectiveness Endpoint – 1 year Mortality, stroke, LT bleed, disabling stroke or mod/severe PVL
REPRISE III
Enrolling: 508 pts
(421 RCT, 87 roll in)
REPRISE II 1-yr f/u TCT 2014
CE Mark Study (Safety & Performance, High Risk) N=120; single arm; 23 & 27mm valve sizes
1⁰ Endpts: 30-day mean pressure gradient & 30-day mortality
1⁰ endpt PCR London Valves 2014
Safety/Performance (High Risk) N=130; single arm
23 & 27mm valve sizes
REPRISE II Extension
REPRISE II Extended Cohort N=250
1⁰ Safety Endpt: 30-day mortality
REPRISE Japan Enrolling
PMDA Trial Approval Confirm Safety & Effectiveness in Japan, High Risk & Inoperable
N=50; single arm; 23, 25 & 27mm valve sizes 1⁰ Endpoints similar to REPRISE III: safety at 30 days, effectiveness at 6 mos
Lotus Clinical Program
31 Jul 2015
Estimated Global TAVR Growth
SOURCE: Credit Suisse TAVI Comment –January 8, 2015. ASP assumption for 2024 and 2025 based on analyst model. Revenue split assumption in 2025 is 45% U.S., 35% EU, 10% Japan, 10% ROW
An All-comers Randomized Clinical Trial Comparing Transcatheter with Surgical AVR
NOTION Randomized Trial
Mean age 79 years Mean STS 3%
NOTION 1 Year in As-Treated Population
Pulmonic Valvuloplasty Catheter
Rubio-Alvarex V, Limon R, Soni J: Intracardiac valvulotomy by means of a catheter Arch Inst Cardiol Mex 23(2):183-92, 1953
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