Structural Heart Disease for Primary Care · DMR cohort (n=127) Left Ventricular Volumes...

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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