TAVR is Superior to Surgical AVR - …az9194.vo.msecnd.net/pdfs/120401/02.03.pdfTAVR is Superior to...

TAVR is Superior to Surgical AVR

Paul S.Teirstein, MD

SCRIPPS CLINIC

Paul S.Teirstein, MD

Chief of CardiologyDirector of Interventional CardiologyDirector Scripps Cardiovascular Institute

Paul Teirstein, MD

Disclosures:

Cordis, Boston, Medtronic, Abbott, Edwards:

Research Grants

SCRIPPS CLINIC

Research Grants

Consultant

Speakers Bureau

The elite surgeon:

--Good looking

--Average ht 6’3”

The basic interventionist

--A little “hunched over”

--Average ht 5’7 and. 1/2”

How can I prove How can I prove TAVR is superior TAVR is superior to traditional AVR?to traditional AVR?

•• Use Level A Evidence (randomized trial data)Use Level A Evidence (randomized trial data)

•• Focus on the PARTNER 1A randomized trial:Focus on the PARTNER 1A randomized trial:

–– High surgical risk:High surgical risk:

·· Predicted risk of operative mortality ≥ 15% (determined by the heart Predicted risk of operative mortality ≥ 15% (determined by the heart team); guideline = STS score ≥ 10team); guideline = STS score ≥ 10

••

PARTNER Study DesignPARTNER Study Design

N = 358InoperableInoperable

ASSESSMENT: ASSESSMENT:

Symptomatic Severe Aortic Stenosis

ASSESSMENT: High-Risk AVR Candidate3,105 Total Patients Screened

ASSESSMENT: High-Risk AVR Candidate3,105 Total Patients Screened

Total = 1,057 patients

2 Parallel Trials: Individually Powered

N = 699 High RiskHigh Risk

ASSESSMENT: ASSESSMENT: Yes No

N = 179

StandardTherapy

ASSESSMENT:

Transfemoral Access

ASSESSMENT:

Transfemoral Access

Not In Study

TF TAVR

Primary Endpoint: All-Cause Mortality Over Length of Trial (Superiority)

Co-Primary Endpoint: Composite of All-Cause Mortalityand Repeat Hospitalization (Superiority)

1:1 Randomization

VS

Yes No

N = 179

TF TAVR AVR

Primary Endpoint: All-Cause Mortality at 1 yr(Non-inferiority)

TA TAVR AVR

VSVS

N = 248 N = 104 N = 103N = 244

ASSESSMENT:

Transfemoral Access

ASSESSMENT:

Transfemoral Access

Transapical (TA)Transfemoral (TF)

1:1 Randomization1:1 Randomization

Yes No

Procedural Outcomes Procedural Outcomes -- TAVR vs. AVRTAVR vs. AVR

Traditional AVR TAVR

Anesthesia time - min 236

Total procedure time - min 133

Aborted procedure - no. (%) 7 (2.0)

Anesthesia time - min 330

Total procedure time - min 230

Aborted procedure - no. (%) 0

*p<0.001

Reoperation for bleeding - no. (%) 2 (0.6)

Intra-procedural death - no. (%) 3 (0.9)

Aortic perforation - no. (%) 0

Index hospitalization (days) 8*

Median ICU stay (days) 3.0*

Reoperation for bleeding - no. (%) 12 (3.4)

Intra-procedural death - no. (%) 1 (0.3)

Aortic perforation - no. (%) 1 (0.3)

Index hospitalization (days) 12

Median ICU stay (days) 5.0

SixSix--Minute Walk TestMinute Walk TestAll Patients (N=699)All Patients (N=699)

Median Distance, meters

P = 0.73 P = 0.002 P = 0.33 P = 0.76

Median Distance, meters

EchocardiographicEchocardiographic Findings Findings AVA (AT)AVA (AT)

Valve Area (cm

2)

TAVR

AVR

Numbers at RiskNumbers at Risk

TAVRTAVR 301301 269269 223223 210210 139139

AVRAVR 290290 224224 162162 151151 110110

Valve Area (cm

p = 0.002 p = 0.003 p = 0.16p = 0.001

EchocardiographicEchocardiographic Findings Findings Mean and Peak Gradients (AT)Mean and Peak Gradients (AT)

Gradient (m

mHg)

Peak Gradient - TAVR

Mean Gradient - TAVR

Peak Gradient - AVR

Mean Gradient - AVR


TAVRTAVR 307307 275275 233233 218218 144144

AVRAVR 295295 228228 168168 155155 112112

Gradient (m

mHg)

AllAll--Cause Mortality (ITT)Cause Mortality (ITT)

Primary Endpoint:Primary Endpoint:AllAll--Cause Mortality at 1 YearCause Mortality at 1 Year

AVR(N = 351)

26.8%

AVR(N = 351)

26.8%

TAVR(N = 348)

24.2%

TAVR(N = 348)

24.2%

Difference -2.6%

Upper 1Upper 1--sided sided 95% CI95% CI 3.0%3.0%

Non-inferiorityP value

= 0.001

Zone of non-inferiority pre-specified

7.0-2.0 -1.0 0.0 6.03.0 4.0 5.0-3.0 1.0 2.0

Non-inferior

Upper one-sided 95% CI

8.0 %

Primary Non-Inferiority Endpoint Met

Zone of non-inferiority pre-specified margin = 7.5%

If two therapies are non inferior and If two therapies are non inferior and one is less invasive,one is less invasive,

then>then>

Even a non-surgeon knows.

then>then>

IT’S SUPERIOR!IT’S SUPERIOR!

Strokes (ITT)Strokes (ITT)Stroke

HR [95% CI] =1.22 [0.67, 2.23]

p (log rank) = 0.517

TAVR

AVR

3.2%

6.0%4.9%

7.7%

Stroke

Months Post Procedure


TAVRTAVR 348348 287287 249249 224224 162162 6565 2828

AVRAVR 351351 246246 230230 211211 160160 6262 3131

DiffusionDiffusion--Weighted MRI StudyWeighted MRI Study

Philipp Kahlert, MDWest German Heart Center Essen

Example of an 82-year-old patient two days after successful TAVI

Pre-TAVI Post-TAVI

Embolic Embolic phenomenonphenomenon

NeuroNeuro--imaging with TAVRimaging with TAVR

JACC 2011N=60

JACC 2010N=30

JACC Int 2010N=25

Circulation 2010N=32

EJCTS 2011N=80

Daneault et al., JACC 2011;58: 2143-50

NeuroNeuro--imaging with AVRimaging with AVR

Ann Thor Surg 2006N=15

Stroke 2004N=37

EJCTS 2005N=30

Circulation 2010N=21

Daneault et al., JACC 2011;58: 2143-50

Cerebral Ischemia After TAVICerebral Ischemia After TAVI

8680

60

80

100

%

224

150

200

250

mm3

New Lesions Lesion Volume

48

0

20

40

60

Edwards CoreValve SAVR

81

61

0

50

100

150

Edwards CoreValve SAVR

Kahlert PK et al. Circulation 2010;121:870-878

DWDW--MRI after TAVRMRI after TAVR

•• 32 pts with TAVI; Diffusion32 pts with TAVI; Diffusion--Weighted MRI at baseline, postWeighted MRI at baseline, post--

procedure, and @ 3 procedure, and @ 3 mosmosprocedure, and @ 3 procedure, and @ 3 mosmos

�� 22 balloon22 balloon--expandable and 10 selfexpandable and 10 self--expanding THV devicesexpanding THV devices

•• New foci of restricted perfusion in 27/32 pts (84%)New foci of restricted perfusion in 27/32 pts (84%)

�� Lesions usually multiple and both hemispheres (embolic)Lesions usually multiple and both hemispheres (embolic)

•• No impairment of No impairment of neuroneuro--cognitive function nor clinical cognitive function nor clinical

neurologic events assoc with MRI defectsneurologic events assoc with MRI defects

�� 80% of MRI defects resolved at 3 80% of MRI defects resolved at 3 mosmos imaging studyimaging study

Kahlert P, Knipp SC, Schlamann M, et al.

Circ 2010;121:870-8 Circ 2010;121:870-8

Later Hazard of Neurologic Event

%%

10

15

TAVR

11

6.7

8.0

%%

Mos

5858

130125

243218

278251

344313

TAVRAVR

0

5

6 12 18 24

AVR

6.7

4.5

51% Procedural51% Procedural

(<10 days)(<10 days)

Timing and Types of Neurologic Events (strokes and TIAs)

AVR

AVR

TAVR

TAVR

AVR

AVR

TAVR

TAVR

AVR

AVR

TAVR

TAVR

AVR

AVR

TAVR

TAVR

AVR

AVR

TAVR

TAVR

AVR

AVR

TAVR

TAVR

AVR

AVR

TAVR

TAVR

00--22daysdays

33--55daysdays

3131--364364daysdays

1111--3030daysdays

66--1010daysdays

22--33yearsyears

11--22yearsyears

Embolic Materialafter TAVR

Embolic MaterialEmbolic MaterialEmbolic MaterialEmbolic Material

Embolic MaterialEmbolic MaterialEmbolic MaterialEmbolic Material

Stroke MessagesStroke MessagesPARTNER 1A PARTNER 1A –– 2 year FU2 year FU

•• Stroke is numerically higher in TAVR Vs. AVRStroke is numerically higher in TAVR Vs. AVR

•• 2 2 yryr: 7.7% : 7.7% VsVs 4.9%, p= 0.524.9%, p= 0.52

•• Absolute stroke difference is lowAbsolute stroke difference is low

•• 2.8%; Number Needed to Harm = 362.8%; Number Needed to Harm = 36•• 2.8%; Number Needed to Harm = 362.8%; Number Needed to Harm = 36

•• If you tell patients the chance of stroke is 57% higher If you tell patients the chance of stroke is 57% higher with TAVR, they will likely choose AVRwith TAVR, they will likely choose AVR

•• If you tell patients the difference in stroke is 7.7% Vs. If you tell patients the difference in stroke is 7.7% Vs. 4.9%, they will likely choose TAVR4.9%, they will likely choose TAVR

Stroke MessagesStroke MessagesTargets for ImprovementTargets for Improvement

•• Many strokes (perhaps close to 50%) occur during the Many strokes (perhaps close to 50%) occur during the

procedureprocedure

•• Distal protection may be helpfulDistal protection may be helpful

•• Many patients in this study had significant risk factors for Many patients in this study had significant risk factors for stroke, ie atrial fibrillationstroke, ie atrial fibrillationstroke, ie atrial fibrillationstroke, ie atrial fibrillation

•• Anti platelet and anti thrombotic regimen has not been Anti platelet and anti thrombotic regimen has not been standardized.standardized.

PARTNER Grading Criteria for PARTNER Grading Criteria for ParavalvularParavalvular AR AR

Circumference = 6″AR = 0.1+0.35 = 0.45″Ratio = 8%Severity = Mild (< 10%)

Circumference = 6″AR = 0.5+0.5 = 1.0″AR = 0.5+0.5 = 1.0″Ratio = 17%Severity = Moderate (10 – 20%)(Trans AR also present)

Circumference = 6″AR = 0.6+1.1 = 1.7″Ratio = 28%Severity = Severe (> 20%)

Images courtesy of Pamela Douglas, MD, FASE

Aortic Regurgitation (AT)Aortic Regurgitation (AT)

p < 0.0001 p < 0.0001 p < 0.0001 p < 0.0001

N = 279 N = 228 N = 231 N = 173 N = 217 N = 156 N = 145 N = 113

Paravalvular Aortic Regurgitation (AT)Paravalvular Aortic Regurgitation (AT)

p < 0.0001 p < 0.0001 p < 0.0001 p < 0.0001

N = 277 N = 226 N = 230 N = 172 N = 216 N = 155 N = 145 N = 112

Total AR and MortalityTotal AR and MortalityTAVR Patients (AT)TAVR Patients (AT)

Mortality

None - Trace

Mild

Moderate - Severe 50.7%

33.4%35.3%

26.2%

p (log rank) < 0.001

Months Post Procedure

Mortality


NoneNone--TrTr 135135 125125 115115 101101 6868 3131 1111

MildMild 165165 139139 121121 111111 7171 3333 1616

ModMod--SevSev 3434 2525 2222 1919 1515 66 22

26.3%

12.7%

26.2%

Paravalular Regurgitation:A great target for innovation

1 Year 2 Years

OutcomeOutcomeAVRAVR

(N = 351)(N = 351)

TAVRTAVR

(N = 348)(N = 348)pp--valuevalue

AVRAVR

(N = 351)(N = 351)

TAVRTAVR

(N = 348)(N = 348)pp--valuevalue

Major Vascular Major Vascular complicationscomplications

13 (3.8)13 (3.8) 39 (11.3)39 (11.3) <0.001<0.001 13 (3.8)13 (3.8) 40 (11.6)40 (11.6) <0.001<0.001

Major bleeding Major bleeding –– no. (%)no. (%) 88 (26.7)88 (26.7) 52 (15.7)52 (15.7) <0.001<0.001 95 (29.5)95 (29.5) 60 (19.0)60 (19.0) 0.0020.002

Other complications at 1 and 2 Years Other complications at 1 and 2 Years All Patients (N = 699)All Patients (N = 699)

New PM New PM –– no. (%)no. (%) 16 (5.0)16 (5.0) 21 (6.4)21 (6.4) 0.440.44 19 (6.4)19 (6.4) 23 (7.2)23 (7.2) 0.690.69

Endocarditis Endocarditis –– no. (%)no. (%) 3 (1.0)3 (1.0) 2 (0.6)2 (0.6) 0.630.63 3 (1.0)3 (1.0) 4 (1.5)4 (1.5) 0.610.61

SVDSVD§§ requiring AVRrequiring AVR 00 00 00 00

MI MI –– no. (%)no. (%) 2 (0.6)2 (0.6) 00 0.160.16 4 (1.5)4 (1.5) 00 0.050.05

Acute kidney inj* Acute kidney inj* –– no. (%)no. (%) 20 (6.5)20 (6.5) 18 (5.4)18 (5.4) 0.570.57 21 (6.9)21 (6.9) 20 (6.2)20 (6.2) 0.750.75

§SVD = Structural Valve Deterioration*Renal replacement therapy

Transfemoral (TF) Vs Transapical (TA)

AllAll--Cause MortalityCause MortalityTransfemoral (N=492)Transfemoral (N=492)

26.4

HR [95% CI] =0.83 [0.60, 1.15]

P (log rank) = 0.25

Months

244 215 188 119 59

248 180 168 109 56

No. at Risk

TAVR

AVR

22.2

AllAll--Cause Mortality at 30 DaysCause Mortality at 30 Days

All Patientsno. of patients ( %)

TF Patientsno. of patients ( %)

TA Patientsno. of patients ( %)

TAVR AVR p-value TAVR AVR p-value TAVR AVR p-value

ITT 12 (3.4) 22 (6.5) 0.07 8 (3.3) 15 (6.2) 0.13 4 (3.8) 7 (7.0) 0.32

AT 18 (5.2) 25 (8.0) 0.15 9 (3.7) 18 (8.2) 0.05 9 (8.7) 7 (7.6) 0.79

AllAll--Cause Mortality at 30 Days Cause Mortality at 30 Days Patient SubgroupsPatient Subgroups

AT 18 (5.2) 25 (8.0) 0.15 9 (3.7) 18 (8.2) 0.05 9 (8.7) 7 (7.6) 0.79

TransfemoralTransfemoralIndex Procedure/Admission Index Procedure/Admission Resource use (perResource use (per--protocol population)protocol population)

Resource CategoryResource CategoryTFTF--TAVRTAVR((N = 234N = 234))

AVRAVR(N= 221)(N= 221)

DifferenceDifference(95% CI)*(95% CI)*

PP--valuevalue

Procedure duration (min) 244±78 330±102 87 (69 – 104) <0.001

Total hospital LOS, days

ICU

10.2 (7)

3.3 (2)

16.4 (12)

5.6 (3)

6.2 (3.8 – 8.2)

2.3 (0.9 – 3.3)

<0.001

<0.001ICU

Non-ICU

Post procedure

3.3 (2)

6.9 (4)

7.4 (5)

5.6 (3)

10.8 (8)

13.5 (10)

2.3 (0.9 – 3.3)

4.0 (2.2 – 5.5)

6.1 (3.7 – 8.0)

<0.001

<0.001

<0.001

Major vasc. complication 13.2% 3.2% 10.1% (5.1 – 15.1) <0.001

Major bleeding 9.4% 22.6% 13.2% (-6.6 to -19.9) <0.001

New pacemaker, n (%) 16 (6.8%) 13 (6.0%) 0.8% (-3.7 – 5.3) 0.73

LOS data are shown as mean (median).*95% CIs from 1,000 bootstrap replications of study data.

DJC6

DJC6 Consider simplifying this table a bit-- new pacemaker doesn't differ and that was reported previously, so perhaps you can get rid of that

Note that some of your confidence intervals have a dash and others have "to"David Cohen, 10/19/2011

$31,192

$4,742$5,773

$60,000

$80,000

Index Admission CostsIndex Admission CostsTransfemoralTransfemoral

$71,955

∆ ∆ ∆ ∆ = ($2,496)P = 0.53

$74,452

$34,863

$14,451

$31,192

$54,228

$0

$20,000

$40,000

TF-TAVR AVR

Procedure Non-Procedure Total MD Fees

1212--Month FollowMonth Follow--up Costsup CostsTransfemoralTransfemoral

∆ = $1,517 Total F/U Costs (12 months)

TF-TAVR $22,251

AVR $21,965

∆ = $287

P = 0.97

∆ = ($2,350)

∆ = 827

∆ = $293

TAVR vs. AVR: TAVR vs. AVR: TransfemoralTransfemoralCost per QALY gainedCost per QALY gained

yr cost (TAVR -AVR)

∆ Cost = - $2210∆ QALYs = + 0.068

ICER = dominant% dominant = 59.7

∆ Cost = - $2210∆ QALYs = + 0.068

ICER = dominant% dominant = 59.7

∆∆∆∆ QALY (TAVR - AVR)

∆∆ ∆∆1-yr cost (TAVR

% <$50,000 per QALY= 74.7

% <$50,000 per QALY= 74.7

Complete Population

Transfemoral (TF) vs Transapical (TA) Transfemoral (TF) vs Transapical (TA) All All Cause MortalityCause Mortality

Transfemoral (TF) subgroupTransfemoral (TF) subgroup Transapical (TA) subgroupTransapical (TA) subgroup

Transapical Aortic Valve Replacement Transapical Aortic Valve Replacement For Critical Aortic Stenosis: Results From For Critical Aortic Stenosis: Results From the Nonthe Non--Randomized Continued Access Randomized Continued Access Cohort of The PARTNER TrialCohort of The PARTNER Trial

Todd M. Dewey, MDon behalf of The PARTNER Trial Investigators

STS 2012 | Fort Lauderdale | Jan 30, 2012

Transapical Enrollment per SiteTransapical Enrollment per Site

Mean # pts enrolled:

PMA-TA (14 sites) = 7.4

Transapical Aortic Valve Replacement For Critical Aortic Stenosis: Results From the NonTransapical Aortic Valve Replacement For Critical Aortic Stenosis: Results From the Non--Randomized Randomized Continued Access Cohort of The PARTNER Trial ... Continued Access Cohort of The PARTNER Trial ... Todd M. Dewey, MDTodd M. Dewey, MD

Transapical Enrollment per SiteTransapical Enrollment per Site

Mean # pts enrolled:

PMA-TA (14 sites) = 7.4

NRCA-TA (22 sites) = 38.3

Transapical Aortic Valve Replacement For Critical Aortic Stenosis: Results From the NonTransapical Aortic Valve Replacement For Critical Aortic Stenosis: Results From the Non--Randomized Randomized Continued Access Cohort of The PARTNER Trial ... Continued Access Cohort of The PARTNER Trial ... Todd M. Dewey, MDTodd M. Dewey, MD

Additional Experience ThroughNon-Randomized Continued Access

500

600

700

800

900

1000

# of Patients Enrolled

Continued Access PeriodRandomized Clinical Trial

PMA-TA = 104

AVR = 103NRCA-TA = 843

0

100

200

300

400

500

May 2007

Sep2009PMA Sep 21, 2011

PMA Data Lock

April 2008

AllAll--Cause Mortality (AT)Cause Mortality (AT)

23.6%25.3%

29.1%

Early Experience

AVRAVR 9292 7676 7171 7070 6767

PMAPMA--TATA 104104 8787 8282 7676 7373

NRCANRCA--TATA 822822 571571 370370 297297 126126

No. at Risk

Later Experience

Stroke (AT)Stroke (AT)

AVRAVR 9292 7272 6767 6666 6363

PMAPMA--TATA 104104 8181 7777 7070 6767

NRCANRCA--TATA 822822 563563 365365 291291 123123

No. at Risk

3.7.%

7.0%

10.8.%

Why is TAVR the Preferred Strategy Compared Why is TAVR the Preferred Strategy Compared to AVR in the High Risk Patient?to AVR in the High Risk Patient?

• Mortality in high risk aortic stenosis patient at 2 years is the same� Mortality in TF subgroup may be lower?

• CVA is only slightly higher at 2 years (numerically, not statistically)

• Anesthesia time cut by 28% (330-236 min)

• Total procedure time cut by 42% (230-133 min)

• ICU stay cut by 40% (5-3 days)

• Total hospitalization days cut by 33% (12-8 days)

SCRIPPS CLINIC

• Total hospitalization days cut by 33% (12-8 days)

• Faster recovery (6 min walk test)

• TF approach is less costly

• Speculation:

• Mortality may be lower than AVR as clinical experience grows

• Mortality may be lower than AVR if paravalvular leak and vascular complications are improved, along with other technology advances

• Stroke may be equivalent to AVR with use of distal protection devices

TAVR Vs AVR: The Future TAVR Vs AVR: The Future

• TAVR is an infant technology� Less invasive than AVR but not yet minimally invasive

• Targets for improvement � Paravalular leak

Better sizing using advanced imaging and larger valvesPost implant dilatation with larger balloonsCircumferential sealing designs to achieve complete annular apposition

SCRIPPS CLINIC

Circumferential sealing designs to achieve complete annular apposition

� StrokeDistal protection deviceSmaller devicesAnti platelet and anti thrombotic therapies

� Vascular complicationsSmaller 14-8Fr delivery devices

� Clinician education/experienceImproved procedural techniqueImproved case selection

esp avoiding cohort C patients-too sick, even for TAVR

Death Incidence (%)

STS 5STS 5--14.914.9STS <5STS <5

Non operative TAVR

STS ≥15STS ≥15

PARTNER 1B PARTNER 1B –– Inoperable patients Inoperable patients

Mortality Stratified by STS Score (ITT)Mortality Stratified by STS Score (ITT)

Death Incidence (%)

Months


Months

2828 2626 2525 2424 1616

1212 88 77 66 55

Months

4343 3232 2323 1919 1515

4747 2929 1919 1414 88

108108 8080 7676 6767 5252

119119 8484 5959 4242 292947

“No, I don’t need my walker!”

86 year old, 3 days post TAVRLevel of Evidence = E

EMOTION!

“Give this thing to someone else!”

Level of Evidence = E

EMOTION!

“I’m getting out of here!”

Level of Evidence = E

EMOTION!

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