role of tavr in low and intermediate risk patient

Role of TAVR in Low and Intermediate RiskRole of TAVR in Low and Intermediate RiskPatient

Michael Mack, M.D.

Baylor Scott & White HealthBaylor Scott & White Health

Dallas, TX

Conflict of Interest DisclosureConflict of Interest Disclosure

Co- PI of COAPT Trial of Abbott VascularCo- PI of COAPT Trial of Abbott Vascular

Steering Committee Intrepid Trial of Medtronic

Co-PI of the PARTNER 3 Trial of Edwards Lifesciences

T rial R isk T otal T AVR S AVR

• Partner 1B Inoperable 358 179 179 (Med)• Partner 1B Inoperable 358 179 179 (Med)

• Partner 1A High 699 348 351

• Corevalve High 795 394 401• CorevalveHR

High 795 394 401

• Partner 2A Intermediate 2032 1011 1021

• SURTAVI Intermediate 1800

• Partner 3 Low 1228

• EvolutR-LR Low 1200

4

• T otal 6884

T rial R isk O utcom e

• Partner 1B• CoreValve

Extreme Risk

Inoperable TAVR > MedicalTherapy

Extreme Risk

• Partner 1A• CoreValve High

Risk

High Risk TAVR=SAVR

Risk

• Partner 2A• SURTAVI

Intermediate Risk TAVR=SAVR• SURTAVI

• Partner 3• Corevalve EvolutR

Low Risk TAVR vs. SAVR

8

• Corevalve EvolutR

80%

100%

60%

80%

20%

40%

0%

20%

20

12

q1

q2

q3

q4

20

13

q1

q2

q3

q4

20

14

q1

q2

q3

q4

20

15

q1

q2

q3

q4

20

16

q1

q2

20

12

q1

20

13

q1

q2

q3

q4

20

14

q1

q2

q3

q4

20

15

q1

q2

q3

q4

20

16

q1

q2

Femoral Transapical Transaortic Other

S ource: S T S /ACC T VT R egistry DatabaseasofO ct18,2016

TVT SitesJan 2012-Sept 2016

TVT SitesJan 2012-Sept 2016

400

476

450

500

252

348

400

250

300

350

400

156

50

100

150

200

0

2012 2013 2014 2015 YT D 2016

S ource: S T S /ACC T VT R egistry DatabaseasofS ept2016S ource: S T S /ACC T VT R egistry DatabaseasofS ept2016

TAVR Centers in USTAVR Centers in US

476Centers

Alaska: 1Hawaii: 1

TAVR Patients in the TVT RegistryTAVR Patients in the TVT Registry

40000

Total ~75,000 Patients

26121

35000

25000

30000

35000

9171

16359

15000

20000

25000

4601

9171

0

5000

10000

2012 2013 2014 2015 Est20162012 2013 2014 2015 Est2016

S ource: S T S /ACC T VT R egistry DatabaseasofA ug2016

The image part with relationship ID rId10 was not found in the file.

The PARTNER 3 TrialThe PARTNER 3 TrialStudy DesignStudy DesignStudy DesignStudy Design

Symptomatic Severe Calcific Aortic Stenosis

Low Risk ASSESSMENT by Heart TeamLow Risk ASSESSMENT by Heart Team(STS < 4(STS < 4%, TF only)%, TF only)


PARTNER 3PARTNER 3RegistriesRegistries


1:1 Randomization(n=1,228)


TF - TAVRTF - TAVR SurgerySurgery

Alternative Access(n=100)

(TA/TAo/Subclavian)


(TA/TAo/Subclavian)TF - TAVR(SAPIEN 3)TF - TAVR(SAPIEN 3)

Surgery(Bioprosthetic Valve)


CT Imaging Sub-Study (n=200)CT Imaging Sub-Study (n=200)

Bicuspid Valves(n=50)


SAVR orTAVR ViV(n=100/25)


Actigraphy/QoL Sub-StudyActigraphy/QoL Sub-Study



PRIMARY ENDPOINT:PRIMARY ENDPOINT:Composite of allComposite of all--cause mortality, allcause mortality, all strokes,strokes,or reor re--hospitalization at 1 yearhospitalization at 1 year postpost--procedureprocedure


(n=100/25)(n=100/25)

Mitral ViV or ViR(n=50/50)


Follow-up: 30 days, 6 mos, 1 year and annually through 10 yearsFollow-up: 30 days, 6 mos, 1 year and annually through 10 years

or reor re--hospitalization at 1 yearhospitalization at 1 year postpost--procedureprocedureor reor re--hospitalization at 1 yearhospitalization at 1 year postpost--procedureprocedure

Current Issues About TAVR in Low Risk PatientsCurrent Issues About TAVR in Low Risk Patients

StrokeStroke

Paravalvular Leak

New PacemakerNew Pacemaker

Durability

Leaflet Immobility/Valve Thrombosis

16


All Strokes at 30 DaysAll Strokes at 30 DaysEdwards SAPIEN ValvesEdwards SAPIEN Valves

PARTNER I and II TrialsPARTNER I and II Trials

Neurologist evaluations (pre- and post)

SAPIENSAPIEN XT SAPIEN 3


Primary Endpoint Events (ITT)Primary Endpoint Events (ITT)At 30 Days and 2At 30 Days and 2 YearsYears

Events (%)Events (%)30 Days30 Days 2 Years2 Years

TAVRTAVR SurgerySurgerypp--value*value*


At 30 Days and 2At 30 Days and 2 YearsYears

TAVRTAVR(n = 1011)(n = 1011)

SurgerySurgery(n = 1021)(n = 1021)

pp--value*value*TAVRTAVR

(n = 1011)(n = 1011)SurgerySurgery

(n = 1021)(n = 1021)pp--value*value*

Death (all-cause)and Stroke (disabling)

6.1 8.0 0.11 19.3 21.1 0.33

DeathDeath

All-cause 3.9 4.1 0.78 16.7 18.0 0.45

Cardiovascular 3.3 3.2 0.92 10.1 11.3 0.38Cardiovascular 3.3 3.2 0.92 10.1 11.3 0.38

Neurological Events

All Stroke 5.5 6.1 0.57 9.5 8.9 0.67

Disabling Stroke 3.2 4.3 0.20 6.2 6.4 0.83

TIA 0.9 0.4 0.17 3.7 2.3 0.09

*Event rates are KM estimates, p-values are point in time

T riGuardEm bolicDeflectionDevice(KeystoneHeart)1

S entinelCerebralP rotectionS ystem (ClaretM edical)2

Em brellaEm bolicDeflectorS ystem (Edw ards

L ifesciences)3

US TrialEnrolling

US Trial CompleteFDA Panel

On the ShelfEnrolling FDA Panel

On the Shelf


Moderate/Severe PVL at 30 DaysModerate/Severe PVL at 30 DaysEdwards SAPIEN ValvesEdwards SAPIEN Valves

PARTNER I and II TrialsPARTNER I and II Trials

SAPIENSAPIEN

XTSAPIEN 3


Other Clinical Endpoints (ITT)Other Clinical Endpoints (ITT)At 30 Days and 2At 30 Days and 2 YearsYears

Events (%)Events (%)30 Days30 Days 2 Years2 Years



At 30 Days and 2At 30 Days and 2 YearsYears

TAVRTAVR(n = 1011)(n = 1011)

SurgerySurgery(n = 1021)(n = 1021)

pp--value*value*TAVRTAVR

(n = 1011)(n = 1011)SurgerySurgery

(n = 1021)(n = 1021)pp--value*value*

RehospitalizationRehospitalization 6.5 6.5 0.99 19.6 17.3 0.22

MIMI 1.2 1.9 0.22 3.6 4.1 0.56MIMI 1.2 1.9 0.22 3.6 4.1 0.56

Major VascularMajor VascularComplicationsComplications

7.9 5.0 0.008 8.6 5.5 0.006

LifeLife--Threatening /Threatening /Disabling BleedingDisabling Bleeding

10.4 43.4 <0.001 17.3 47.0 <0.001Disabling BleedingDisabling Bleeding

10.4 43.4 <0.001 17.3 47.0 <0.001

AKI (Stage III)AKI (Stage III) 1.3 3.1 0.006 3.8 6.2 0.02

New Atrial FibrillationNew Atrial Fibrillation 9.1 26.4 <0.001 11.3 27.3 <0.001

New PermanentNew PermanentPacemakerPacemaker

8.5 6.9 0.17 11.8 10.3 0.29

ReRe--interventionintervention 0.4 0.0 0.05 1.4 0.6 0.09

EndocarditisEndocarditis 0.0 0.0 NA 1.2 0.7 0.22EndocarditisEndocarditis 0.0 0.0 NA 1.2 0.7 0.22

*Event rates are KM estimates, p-values are point in time


The PARTNER 3 TrialThe PARTNER 3 TrialStudy DesignStudy DesignStudy DesignStudy Design

Symptomatic Severe Calcific Aortic Stenosis







TF - TAVRTF - TAVR SurgerySurgery


(TA/TAo/Subclavian)


(TA/TAo/Subclavian)TF - TAVR(SAPIEN 3)TF - TAVR(SAPIEN 3)













(n=100/25)(n=100/25)



Follow-up: 30 days, 6 mos, 1 year and annually through 10 yearsFollow-up: 30 days, 6 mos, 1 year and annually through 10 years

or reor re--hospitalization at 1 yearhospitalization at 1 year postpost--procedureprocedureor reor re--hospitalization at 1 yearhospitalization at 1 year postpost--procedureprocedure

30 days Post TAVRAsymptomatic

Change Mean Gradient - 12

30 Days Post Coumadin

Change Mean Gradient - 12

405/460 (88%) 4D CT

JACC Online

37

JACC Online

4.69.190%

100%

4.69.1

16.322.4

35

60%

70%

80%

90%

28.830.6

29.8 29.429

30%

40%

50%

60%

29.429

0%

10%

20%

2012 2013 2014 2015 20162012 2013 2014 2015 2016

SAVR TAVR

4.69.190%

100%

4.69.1

16.322.4

34 40 45 55 6560%

70%

80%

90%

28.830.6

29.8 29.429

30%

40%

50%

60%

29.429 27 25 25 25

0%

10%

20%

2012 2013 2014 2015 2016 2017 2018 2019 20202012 2013 2014 2015 2016 2017 2018 2019 2020

SAVR TAVR

The TAVR train has left the station on the way to Low Risk

TAVR is not real surgeryTAVR is not real surgery

Bruce Lytle MD

TMVRTMVR

The decline of big case surgerybegan before we startedtraining, it was always atraining, it was always aproduct of the age in which itdeveloped and that age haspassed, and it will decline

Vince Gaudiani MD

Big Case SurgeryBig Case Surgery

Whipple ProceduresRadical MastectomyOpen AAAOpen AAAOpen Esophagectomy

role of tavr in low and intermediate risk patient

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