Post on 10-Jul-2020
Timothy Byrne, D.O., FACC
Abrazo Market Medical Director, Interventional Cardiology
Assistant Professor of Medicine, Banner University Phoenix
Structural Heart Disease for
Primary Care
2
Disclosures
• Abbott Vascular
-Consultative Fees and Honoraria
• Medtronic Inc.
-Consultative Fees and Honoraria
-International Proctor
3
Objectives
• Understand current Structural Heart Procedures
-Transcatheter Aortic Valve Replacement (TAVR)
- MitraClip Transcatheter therapy
- Watchman Device- Left Atrial Appendage
Occlusion
• TVT Registry Data Collection Requirements
• NCD Guidelines for FDA Approved Devices
• Role of Primary Care Provider in the “Heart Team”
4
Case #1
• HPI: 84 y/o male presents for evaluation of
progressive DOE. Now unable to perform his usual
ADL’s.
• PMH: 4V CABG 1993, AAA repair 1987, HTN,
Hypercholesterolemia, CKD stage III
• PE: Harsh crescendo decrescendo murmur with a
late systolic peak, bibasilar rales, JVP 10cm H2O, 3+
pretibial edema
5
6
7
What happens next?
• Echo meets criteria for Severe Aortic Stenosis:
– AVA <1.0 cm2
– Mean Gradient > 40 mmHg
– Jet velocity > 4.0 m/sec (PG >64 mmHg)
• Cardiologist confirms Sxs, calculates STS risk score
http://riskcalc.sts.org/stswebriskcalc/calculate
and refers to Cardiovascular surgeon or Heart Team
• Cardiovascular Surgeon determines SAVR vs TAVR
8
TVT Screening Requirements for TAVR
• 2 Cardiovascular surgical consultations
• Cardiac catheterization with PCI as indicated within
one year of implant date
• 12 lead EKG
• Carotid US
• Ankle Brachial Index (ABI)
• PFT’s (FEV1 & DLCO)
• CTA Heart, Chest, Abdomen & Pelvis
• Labs (CBC, CMP, CKMB, troponin, PT/INR, BNP)
• 5 meter walk test (Frailty)
• Kansas City Cardiomyopathy Questionnaire (KCCQ)
9
TAVR Implant Day
Medtronic Evolut Pro
Boston Scientific Lotus Edge
Edwards Sapien 3
10
11
12
13
CoreValve Clinical Evidence
Evolut Platform Clinical Evidence | Medtronic - Confidential
CoreValve TAV
Self-expanding nitinol frame
Porcine pericardium
Supra-annular valve
CoreValve evidence represents early implanter experience with 1st generation valve and randomization to TAVR or SAVR.
CoreValve US Pivotal High Risk Trial:
Primary endpoint = All-Cause Mortality at 12 Months
Valve performance outcomes out to 5 years
SURTAVI Intermediate Risk Trial:
Primary endpoint = All-Cause Mortality or Disabling Stroke at 24 Months
14
CoreValve US Pivotal High Risk RCTOnly transcatheter Valve to Demonstrate Superiority to SAVR
Evolut Platform Clinical Evidence | Medtronic - Confidential
All Cause Mortality
P <0.001 for non-inferiority
P = 0.04 for superiority
Adams, et al. NEJM, 2014.
TAVR 390 377 353 329
SAVR 367 341 297 274
19.1%
14.2%
15
CoreValve US Pivotal High Risk RCTSustained Hemodynamics Through 5 Years
Evolut Platform Clinical Evidence | Medtronic - Confidential
TAVR AVG 391 363 303 250 193 152 112
SAVR AVG 359 317 230 188 141 114 88
TAVR EOA 384 343 284 238 182 144 99
SAVR EOA 353 289 210 174 134 106 84
Gleason, et al. JACC, 2018.
P <0.01 for TAVR vs. SAVR at all follow-up time points.
16
CoreValve US Pivotal High Risk RCTDurability
Evolut Platform Clinical Evidence | Medtronic - Confidential
Gleason, et al. JACC, 2018.
TAVR (N=390) SAVR (N=354) p Value
Structural Valve Deterioration (SVD)* 9.5 (37/390) 26.6 (94/354) <0.001
Moderate hemodynamic SVD 9.2 (36/390) 26.6 (94/354) <0.001
Mean gradient (MG) at any time of ≥20, but <40 mmHg 5.4 (21/390) 25.7 (91/354) <0.001
Change in MG from discharge/1 month of ≥10, but <20 mmHg
1.5 (6/390) 5.4 (19/354) 0.004
Moderate central AR (new from discharge) 3.3 (13/390) 0.8 (3/354) 0.022
Severe hemodynamic SVD 0.8 (3/390) 1.7 (6/354) 0.322
Mean gradient (MG) at any time of ≥40 mmHg 0.3 (1/390) 1.1 (4/354) 0.197
Change in MG from discharge/1 month of ≥20 mmHg 0.5 (2/390) 0.8 (3/354) 0.673
Severe central AR (new from discharge) 0.3 (1/390) 0.0 (0/354) >0.999
Measures of Structural Valve Deterioration at 5 Years
*SVD defined by Capodanno et al., Eur Heart J, 2017.
Values are % (n/N).
Significantly lower occurrence of moderate hemodynamic SVD as compared to SAVR at 5 years (p <0.001).
17
SurtAVi Intermediate Risk RCTTAVR is nonInferior to surgery in Intermediate Risk Subjects
Evolut Platform Clinical Evidence | Medtronic - Confidential
Popma, TCT, 2018.
18Popma, TCT, 2018.
SurtAVi Intermediate Risk RCTKCCQ Summary Score
Evolut Platform Clinical Evidence | Medtronic - Confidential
19Popma, TCT, 2018.
SurtAVi Intermediate Risk RCT6-Minute walk test
Evolut Platform Clinical Evidence | Medtronic - Confidential
20
Case #2 MJ
HPI: 75 y/o former smoker Caucasian male rock singer
presents to your clinic for evaluation of NYHA Fc III
exertional breathlessness symptoms.
PMH: previous drug use, HIV neg, multiple sex partners
PE: Harsh crescendo decrescendo murmur with a late
systolic peak
21
22
Balloon Expandable TAVR
23
About the Sapien 3 Valve
• Bioprosthetic
– Long term durability data pending
– Expected to last as long as
surgical valves
• Bovine pericardium
– Treated to prevent calcification or
tissue breakdown
– Tissue is not living, your body
won’t attack it
• Cobalt chromium alloy stent
frame
– MRI Safe
– Won’t set off security at the
airport
• PET Fabric skirt for sealing
26
Study Flow and Follow Up
27
Primary Endpoints
28
All-Cause Mortality
29
All Stroke
30
Death or Disabling Stroke
31
Case #3
• HPI: 75 y/o Caucasian male presents with increased
fatigue, decreased exercise tolerance, NYHA Fc IIIa
CHF symptoms
• PMH: Acute on chronic systolic congestive heart
failure, pulmonary HTN, AI s/p SAVR 2006, Dilated
non-ischemic cardiomyopathy with EF of 25%, hx of
VT and cardiac arrest s/p BIV AICD implantation – on
amiodarone, paroxysmal A-fib, LBBB
• PE: 3/6 Holosystolic murmur at the cardiac apex,
soft S3, bibasilar rales, 2+ pitting pretibial edema
32
Echo Images
33
Echo Images
34
What happens next?
• Echo meets criteria for Severe Mitral Regurgitation:
– MVOA >4.0 cm2
• Cardiologist confirms Sxs, calculates STS risk score
http://riskcalc.sts.org/stswebriskcalc/calculate
and refers to Cardiovascular surgeon or Heart Team
• Heart Team determines SMVR vs TMVR
35
TVT Screening Requirements for
TMVR • 1 Cardiovascular surgical consultation
• Cardiac catheterization with PCI as indicated within
one year of implant date
• 3D TEE
• 12 lead EKG
• Carotid US
• Ankle Brachial Index (ABI)
• PFT’s (FEV1 & DLCO)
• Labs (CBC, CMP, CKMB, troponin, PT/INR, BNP)
• 5 meter walk test (Frailty)
• Kansas City Cardiomyopathy Questionnaire (KCCQ)
36
MitraClip Transcatheter Therapy
37
Total MR Patients1,2
MR Grade ≥3+3,4
4,100,000
1,700,000
Annual MV Surgery5
Annual Incidence3
(MR Grade ≥3+)250,000
30,000
1,670,000 Untreated Large
and Growing
Unmet Need
1. US Census Bureau. Statistical Abstract of the US: 2006, Table 12.2. Nkomo et al. Burden of Valvular Heart Diseases: A Population-based Study, Lancet, 2006; 368: 1005-11.3. Patel et al. Mitral Regurgitation in Patients with Advanced Systolic Heart Failure, J of Cardiac Failure, 2004.4. ACC/AHA 2008 Guidelines for the Management of Patients with Valvular Heart Disease, Circulation: 20085. Gammie, J et al, Trends in Mitral Valve Surgery in the United States: Results from the STS Adult Cardiac Database, Annals of Thoracic Surgery 2010.
Mitral Regurgitation 2009 U.S. Prevalence
A Largely Untreated Population
38
TMVR Trial Design – 2017
Background & Lessons
1. The complexity of mitral valve disease (MR) has provoked an equally complex multi-device transcatheter approach in an effort to simulate the varied surgical procedures which are required to achieve optimal clinical outcomes.
Transcatheter MV Repair: Device Landscape 2017Edge-to-edge
• MitraClip***
• MitraFlex
Coronary sinus annuloplasty
• Cardiac Dimensions Carillon**
• Cerclage annuloplasty
Direct annuloplasty and
basal ventriculoplasty
• Mitralign TAMR**
• Valtech Cardioband**
• GDS Accucinch*
• Millipede IRIS*
• MVRx ARTO*
• Mardil BACE*
• Mitraspan*
• Valcare Amend*
• Micardia enCor
• Cardiac Implants RDS
• QuantumCor (RF)
MV replacement (cont)
• MitralHeal
• HT Consultant Saturn
• Lutter valve
• Transcatheter Technologies
Tresillo
• Venus
• Verso
• Transmural Systems
Other approaches
• NeoChord DS 1000**
• Harpoon neochords*
• Babic chords*
• Middle Peak Medical*
• St. Jude leaflet plication*
• Cardiosolutions Mitra-Spacer*
• Valtech Vchordal
• Mitralix
MV replacement
• Edwards CardiAQ*
• Edwards Fortis*
• Neovasc Tiara*
• Abbott Tendyne*
• Medtronic Intrepid*
• HighLife*
• MValve*
• Caison*
• NCSI NaviGate
• St. Jude
• Micro Interventional
• Valtech CardioValve
• ValveXchange
• MitrAssist
• Braile Quattuor
• Cephea
• Direct Flow
• Sinomed Accufit*In patients *CE mark *FDA approved
40
TMVR Trial Design – 2017
Background & Lessons
1. The complexity of mitral valve disease (MR) has provoked an equally complex multi-device transcatheter approach in an effort to simulate the varied surgical procedures which are required to achieve optimal clinical outcomes.
2. The controversy of surgical repair vs. replacement for MR
‘rages on’, in part fueled by high recurrence after repair (e.g.
annuloplasty in 2ry MR) and high mortality/complications
after surgical MVR.
41
SMR Trial: Failure at 2 YearsFailure = Death, MR ≥2+ or MV reoperation
Goldstein D et al. NEJM 2016;374:344-353
42
Mitral Regurgitation
• MR is caused by
malcoaptation of the
mitral valve leaflets
– Degenerative MR (primary)
– Functional MR (secondary)
• Irreversible if not repaired
• Ultimately results in CHF
• MitraClip offers a
treatment option for
prohibitive surgical risk
patients
NormalMitral Valve
DegenerativeMR: Prolapse
DegenerativeMR: Flail
Functional MR
43
History of TMVr
• Double-orifice suture technique developed by
Prof. Ottavio Alfieri
• First published results in 1998 illustrated proven benefit
• Suggested procedure best suited for minimally
invasive approach
• Dr. Fred St. Goar, interventional cardiologist had
patient successfully treated with edge-to-edge surgery
• Conceived several ideas for percutaneous valve repair
• Founded Evalve 1999 to develop devices to treat
valvular disease
44
Clinical Experience: Prohibitive surgical risk
DMR cohort (n=127)
Left Ventricular Volumes
Hospitalizations for Heart Failure
Left Ventricular End Diastolic Volume Left Ventricular End Systolic Volume
(N = 69)Paired
Data (N=69)
0.67
0.18
0.0
0.2
0.4
0.6
0.8
1.0
1 Year Priorto MitraClip
1 Year PostDischarge
HF
Ho
sp
itali
zati
on
Rate
per
Pati
en
t Y
ear
73% Reduction
125
109
60
70
80
90
100
110
120
130
140
Baseline 1 Year
Vo
lum
em
L
-16 mL
0
49
46
30
35
40
45
50
55
60
Baseline 1 Year
0
-3 mL
0
1+
3+
4+
2+Clinically Important Reduction
of Mitral Regurgitation
I
II
IV
IIIClinically Important Improvement
in NYHA Functional Class
Clinically Important Reduction
in the Rate of Hospitalization
for Heart Failure
Clinically Important Reverse
LV Remodeling
45
Increasing Mitral
Regurgitation
Increase Load/Stress
Muscle Damage/Loss
Dysfunction of Left
Ventricle
Dilation of Left Ventricle
1 year mortality
up to
57%1
1. Cioffi G, et al. European Journal of Heart Failure 2005 Dec;7(7):1112-7.2. Goliasch G et al. EHJ 2018;39:39-46. Graph courtesy of Dr. GStone.
P<0.001
No/mild SMR
1.0
Su
rviv
al
Moderate SMR
Severe SMR
0.8
0.6
0.4
0.2
0 2 4Years
6 8
SEVERE SECONDARY MR IS AN
Secondary MR is a Predictor of Mortality
See Important Safety Information referenced within. ©2019 Abbott. All rights reserved. AP2947501-US Rev B
INDEPENDENT PREDICTOR OF MORTALITY2
Prospective study: 576 pts with HFrEF 21% severe FMR, 32% mod FMR
46
The First and ForemostIN THE TREATMENT OF MITRAL REGURGITATION
15+ Years of Dedication to the Treatment of MR
2005 2006 2007 2008 2012 2013 2014 2015 2016 2017 2018 2019
EVEREST IFeasibility Study55 Patients Enrolled2003-2006
EVEREST IIRCT279 Patients Enrolled2005-2008
EVEREST II HIGH RISK STUDYSingle-Arm Study78 Patients Enrolled2007-2008
FIRST IN MAN
2003 2004
ACCESS EUROPESingle-Arm Study567 Commercial Patients Enrolled
2009-2012
2009 2010 2011
EVEREST II REALISMContinued Access965 Patients Enrolled2009-2014
COAPTRCT614 Patients Enrolled2013-2017
COAPT CASContinued AccessCurrently Enrolling
2017-Present
STS/ACC TVT REGISTRY 2013-Present
MITRACLIP POST-APPROVAL STUDYCommercial Registry1998 Patients Enrolled2013-2016
MITRA.FR*RCT304 Patients Enrolled2014-2017
MATTERHORN* & RESHAPE-HF2*RCTCurrently Enrolling
2015-Present
EXPAND STUDYCommercial RegistryCurrently Enrolling
CE MARK APPROVAL
FDA APPROVALFor PMR
AVAILABLEIN CANADA 2nd GENERATION
MITRACLIP
AVAILABLE IN JAPAN
3rd GENERATION MITRACLIP
MITRACLIP JAPANSingle-Arm Study30Patients2015-2016
JAPAN PMSCommercial RegistryCurrently Enrolling
*Investigator-sponsored studies.
Commercial approvals
New generation launch
Clinical Study
FDA APPROVALFor SMR
COAPT Data Release at TCT
See Important Safety Information referenced within. ©2019 Abbott. All rights reserved. AP2947501-US Rev B
47
MitraClip™ Improves Survival
38%
RELATIVE RISK REDUCTION IN MORTALITY
5.9
# NEEDED TO TREATTO PREVENT 1 DEATH
MR IS A CAUSE OF DEATH—THE COAPT TRIAL SHOWS THAT MR IS NOT JUST A MARKER
0
20
40
60
0 3 6 18 21 24
Pat
ien
ts W
ho
Die
d fr
om
An
y C
ause
(%)
9 12 15
Months Since Randomization
Control Group46.1%
Device Group29.1%
ALL CAUSE MORTALITY
Hazard ratio, 0.62 (95% CI, 0.46-0.82)P<0.001
See Important Safety Information referenced within. ©2019 Abbott. All rights reserved. AP2947501-US Rev B
48
COR LOE
I A
Patients with chronic secondary MR (stages B to D) and HF with reduced LVEF should receive standardGDMT therapy for HF, including ACE inhibitors, ARBs, beta blockers, and/or aldosterone antagonists asindicated
I ACardiac resynchronization therapy with biventricular pacing is recommended for symptomatic patients with chronic severe secondary MR (stages B to D) who meet the indications for device therapy
IIa CMitral valve surgery is reasonable for patients with chronic severe secondary MR (stages C and D) who are undergoing CABG or AVR.
IIb B[Surgical] mitral valve repair or replacement may be considered for severely symptomatic patients (NYHA class III to IV) with chronic severe secondary MR (stage D) who have persistent symptoms despite optimal GDMT for heart failure
IIb CMV repair may be considered for patients with chronic moderate secondary MR (stage B) who are undergoing other cardiac surgery
COR= Class (strength) of recommendation LOE= Level of evidence. Nishimura RA et al. J Am Coll Cardiol 2017;70:252–89.
Current Heart Failure Guidelines: GDMT and CRT
NO TREATMENT OPTIONS FOR PATIENTS WHO REMAIN SYMPTOMATIC DESPITE BEING ON MAXIMALLY TOLERATED
GDMT
See Important Safety Information referenced within. ©2019 Abbott. All rights reserved. AP2947501-US Rev B
49
COAPT Sets a New Standard with NNT of 5.9
# NEEDED TO TREAT (NNT) TO PREVENT ONE DEATH FROM ANY CAUSE
Trial Name Mean Follow-up
Drug/Device Name
PARADIGM-HF1
27 MonthsEntresto (GDMT)
COAPT3
19.1 MonthsMitraClip + GDMT
CARE-HF2
29.4 MonthsCRT + GDMT
1. McMurray JJV, Packer M, Desai AS, et al. N Engl J Med 2014;371:993-1004.2. Stone G, Lindenfeld J, Abraham W, et al. DOI: 10.1056/NEJMoa1806640.3. Manually calculated from Table 2: Cleland JG et al. N Engl J Med 2005;352:1539-1549.
*Data from different trials with similar follow up periods; incremental benefits due to test drug/device above background therapy.
40
5.910
See Important Safety Information referenced within. ©2019 Abbott. All rights reserved. AP2947501-US Rev B
50
MitraClip™ Improves Survival
38%
RELATIVE RISK REDUCTION IN MORTALITY
5.9
# NEEDED TO TREAT TO PREVENT 1 DEATH
0
20
40
60
0 3 6 18 21 24
Pat
ien
ts W
ho
Die
d fr
om
An
y C
ause
(%)
9 12 15
Months Since Randomization
ControlGroup46.1%
Device Group29.1%
ALL CAUSE MORTALITY
Hazard ratio, 0.62 (95% CI, 0.46-0.82)P<0.001
See Important Safety Information referenced within. ©2019 Abbott. All rights reserved. AP2947501-US Rev B
51
MitraClip™ Reduces Heart Failure
Hospitalizations
47%
RELATIVE RISK REDUCTION IN HF HOSPITALIZATIONS
3.1
# NEEDED TO TREAT TO PREVENT 1 HF HOSPITALIZATION
REDUCES HOSPITALIZATIONS FOR HF
0
50
100
150
200
250
300
0 3 6 18 21 24
Tota
l No
. of
Ho
spit
aliz
atio
ns
for
He
art
Failu
re
9 12 15
Months Since Randomization
Hazard ratio, 0.53 (95% CI, 0.40-0.70)P<0.001
Control Group 283 in 151 pts
Device Group 160 in 92 pts
1. Stone GW, Lindenfeld J, Abraham WT, et al. Transcatheter mitral-valve repair in patients with heart failure. N Engl J Med. September 23, 2018. DOI: 10.1056/NEJMoa1806640.
See Important Safety Information referenced within. ©2019 Abbott. All rights reserved. AP2947501-US Rev B
See Important Safety Information referenced within. ©2019 Abbott. All rights reserved. AP2947501-US Rev B
53
MitraClip™ Reduces Secondary MRMR SEVERITY
4+3+2+≤1+
0%
20%
40%
60%
80%
100%
Baselinen: 311
30 daysn: 257
6 mon: 218
12 mon: 175
24 mon: 76
0%
Note: Unpaired data.
20%
40%
60%
80%
100%
99.1% OF MITRACLIP PATIENTS HAD MR ≤ 2+ AT 24 MONTHS
MITRACLIP GDMT
Baselinen: 302
30 daysn: 273
6 mon: 240
12 mon: 210
24 mon: 114
See Important Safety Information referenced within. ©2019 Abbott. All rights reserved. AP2947501-US Rev B
54
MitraClip™ is Safe
PRIMARY SAFETY ENDPOINTFreedom from Device-related Complications within 12 months (P<0.001)
MitraClip Procedures Attempted N=293
Device-related complications 9 (3.4%)
- Single leaflet device attachment 2 (0.7%)
- Device embolization 1 (0.3%)
- Endocarditis requiring surgery 0 (0.0%)
- Mitral stenosis requiring surgery 0 (0.0%)
- Left ventricular assist device implant 3 (1.2%)
- Heart transplant 2 (0.8%)
- Any device-related complication requiring non-elective CV surgery
1 (0.3%)
*KM estimate.**Calculated from Z test with Greenwood’s method of estimated variance against a pre-specified objective performance goal of 88%.
80%
70%
60%
50%
90%
100% 96.6%*
88% OPC
94.8% [95% LCL]**
Stone GW et al. TCT 2018.
See Important Safety Information referenced within. ©2019 Abbott. All rights reserved. AP2947501-US Rev B
56
Severe Mitral Regurgitation
57
58
59
60
61
62
63
• 70 year old female
• CAD with PCI – 2016, COPD, HTN, Anemia, stroke
• Paroxsysmal Atrial Fibrillation
• Recurrent GI bleeds while on oral anticoagulation
– Required hospitalizations and blood transfusions
• CHA2DS2VASc risk score=6 (CHF, HTN, Age, PVD,
Female)
• Stroke risk 9.8% per year
• HAS-BLED risk score=5 (HTN, Bleeding hx, stroke,
Age, Med Apixaban)
• Shared decision making documented between
PCP/Cardiologist/patient
64
Watchman Procedure
65
0 and 45 Degree Views
Baseline TEE Views
0 DegreeWidth: 21.2mmDepth: 25.8mm
45 DegreeWidth: 23.5mmDepth: 31.0 mm
90 and 135 Degree Views
Baseline TEE Views
90 DegreeWidth: 23.7 mmDepth: 30.0 mm
135 DegreeWidth: 21.7 mmDepth: 24.7 mm
Device Size
27 mm WATCHMAN
Post Implant
19.7 mm
0 Degree 45 Degree
20.2 mm
Post Implant
90 Degree 135 Degree
21.0 mm 21.5 mm
71
72
73
74
75
WATCHMAN™ LAA Closure Device
Frame: Nitinol structure• Available sizes:
– 21, 24, 27, 30, 33 mm (diameter)
– 10 Fixation anchors around device perimeter engage LAA tissue
– Contour shape accommodates most LAA anatomy
Fabric Cap: (PET) Fabric Polyethylene terephthalate
• Prevents harmful emboli from exiting during the healing process
• 160 micron filter
Anchors
PET fabric
Patient Selection ConsiderationsWATCHMAN™ IFU and CMS Coverage
• The WATCHMAN Device is indicated to reduce the risk of thromboembolism from the left atrial appendage in patients with non-valvularatrial fibrillation who:
• Are at increased risk for stroke and systemic embolism based on CHADS2 or CHA2DS2-VASc scores and are recommended for anticoagulation therapy;
• Are deemed by their physicians to be suitable for warfarin; and
• Have an appropriate rationale to seek a non-pharmacologic alternative to warfarin, taking into account the safety and effectiveness of the device compared to warfarin
• CHADS2 score ≥2 or a CHA2DS2-VASc score ≥3
• Patients must be suitable for short-term warfarin, but deemed unable to take long-term oral anticoagulation
• Documented evidence of a formal shared decision interaction between the patient and an independent, non-interventional physician
CMS CoverageFDA Indication
Patient Selection Considerations
78
ACC, HRS, SCAI Consensus Memo to CMS Contraindications to Long-Term Warfarin Therapy
WATCHMAN is Not Just For Those at Risk of Bleeding
The CMS NCD for LAAC (20.34) indicates that patients must have "A suitability for short-term warfarin but deemed unable to take long-term oral anticoagulation…."
Although not part of the NCD, the professional societies (HRS/ACC/SCAI) recommended the list below to CMS during the public comment period, to describe the population they view as
contraindicated to long-term anticoagulation.
Source: ACC, HRS, SCAI LAAC NCD consensus memo to CMS
Implant Success & Warfarin Cessation
p = 0.04
Study 45-day 12-month
PROTECT AF 87% >93%
CAP 96% >96%
PREVAIL 92% >99%
Implant success defined as deployment and release of the device into the left atrial appendage
Warfarin Cessation PREVAIL Implant
Success
No difference between new
and experienced operators
Experienced Operators
• n=26
• 96%
New Operators
• n=24
• 93% p = 0.28
PROTECT AF and CAP: Reddy, VY et al. Circulation. 2011;123:417-424.
PREVAIL: Holmes, DR et al. JACC 2014; 64(1):1-12.
All Studies: Favorable Procedural Safety Profile for 7-day Safety Events
9.9%
4.8%4.1% 4.1% 3.8%
0.0%
2.0%
4.0%
6.0%
8.0%
10.0%
12.0%
CAP PREVAIL CAP2
Patients with Safety
Event (%)
PROTECT AF
1st Half 2nd HalfN=232 N=231 N=566 N=269 N=579
All Device and/or procedure-related serious adverse events within 7 Days including composite of vascular complications such as cardiac perforation, pericardial effusion with tamponade, ischemic stroke, device
embolization, and other vascular complications such as PE not necessitating intervention, AV fistula, major bleeding requiring transfusion, pseudoaneurysm, hematoma and groin bleeding1
FDA Panel October 2014.
2.31.5
1.00.5
3.8
2.2 2.4
1.2
0
1
2
3
4
5
6
Primary Efficacy All Stroke CV orUnexplained Death
Disabling Stroke
PROTECT AF 4 Year:Results
Rat
e p
er
10
0 p
atie
nt
year
s PS = 96%
40% lower
WATCHMAN
N=463Warfarin
N=244PN = Posterior Probability for Non-InferiorityPs = Posterior Probability for SuperiorityDisabling or fatal strokes were those with an MRS of 3-6 post stroke. Non-disabling were those with an MRS of 0-2 post stroke.For Bayesian analysis, a posterior probability of 97.5% represents non-inferiority; ≥95% represents superiority.
PN > 99%
32% lowerPS = 99%
60% lower
PS = 98%
63% lower
Reddy, VY et al. JAMA. 2014; 312(19):1988-1998.
Meta-Analysis Shows Comparable Primary Efficacy Results to Warfarin
Source: Holmes DR, et al. Holmes, DR et al. JACC 2015; In Press. Combined data set of all PROTECT AF and PREVAIL WATCHMAN patients versus chronic warfarin patients
HR p-value
Efficacy 0.79 0.22
All stroke or SE 1.02 0.94
Ischemic stroke or SE 1.95 0.05
Hemorrhagic stroke 0.22 0.004
Ischemic stroke or SE >7 days 1.56 0.21
CV/unexplained death 0.48 0.006
All-cause death 0.73 0.07
Major bleed, all 1.00 0.98
Major bleeding, non procedure-related 0.51 0.002
0.01 0.1 1 10
Favors WATCHMAN Favors warfarin
Hazard Ratio (95% CI)
PROTECT AF/PREVAIL Pooled Analysis: Less Bleeding with WATCHMANTM Device 6 Months Post-Implant
50
60
70
80
90
100
0 7
Time (months)
Free of Major
Bleeding Event (%)
6 6046 1808 45
Time (days)
Warfarin
+Aspirin
Warfarin
+Aspirin
Aspirin+
ClopidogrelAspirin
WATCHMANWarfarin
Definition of bleeding: Serious bleeding event that required intervention or hospitalization according to adjudication committee
71%Relative Reduction
In Major Bleeding
after cessation of
anti-thrombotics
HR = 0.29
p<0.001
WATCHMAN Device Arm Drug Protocol
Price, MJ. Avoidance of Major Bleeding with WATCHMAN Left Atrial Appendage Closure Compared with Long-Term Oral Anticoagulation : Pooled Analysis of the PROTECT-AF
and PREVAIL RCTs. TCT 2014 (abstract)
Directions for Use (DFU)Post Procedure Information
86
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