craig r. smith, md on behalf of the partner trial investigators

Craig R. Smith, MDon behalf of The PARTNER Trial Investigators

Transcatheter vs. Surgical Aortic Valve Replacement in High Risk Patients with Severe Aortic Stenosis: Results From The PARTNER Trial

ACC 2011 | New Orleans | April 3, 2011

Craig R. Smith, MD

PARTNER Trial sponsor (Edwards LifeSciences) reimburses customary travel and other expenses

Presenter Disclosure Information Presenter Disclosure Information for PARTNER at ACC April 3, 2011for PARTNER at ACC April 3, 2011

BackgroundBackground

• Surgical aortic valve replacement (AVR) is the standard of care for treating patients with symptomatic aortic stenosis who are candidates for operation.

• Although transcatheter aortic valve replacement (TAVR) reduces mortality in patients who cannot have AVR, there have been no randomized trials comparing TAVR to AVR in patients who are at high-risk for operation.

PurposePurpose

To compare the safety and effectiveness of TAVR (either transfemoral or transapical) to surgical AVR in high-risk, operable patients with symptomatic, severe aortic stenosis.

N = 699 N = 358High RiskHigh Risk InoperableInoperable

PARTNER Study DesignPARTNER Study Design

Symptomatic Severe Aortic StenosisSymptomatic Severe Aortic Stenosis

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


Total = 1,057 patients

2 Parallel Trials: Individually Powered

StandardTherapyStandardTherapy

ASSESSMENT: Transfemoral

Access


Access

Not In StudyNot In Study

TF TAVRTF TAVR

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

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



1:1 Randomization1:1 Randomization

VS

YesYes NoNo

N = 179 N = 179

Inoperable PARTNER CohortInoperable PARTNER CohortPrimary Endpoint: Primary Endpoint: All-Cause MortalityAll-Cause Mortality

Numbers at RiskNumbers at Risk

TAVITAVI 179179 138138 122122 6767 2626 Standard RxStandard Rx 179179 121121 8383 4141 1212

Standard Rx

TAVI

All-

caus

e m

orta

lity

(%)

Months

∆ at 1 yr = 20.0%NNT = 5.0 pts 50.7%

30.7%

HR [95% CI] =0.54 [0.38, 0.78]

P (log rank) < 0.0001

Leon et al, NEJM 2010; 363:1597-1607

N = 179

N = 358InoperableInoperable

StandardTherapyStandardTherapy


Access


Access

Not In StudyNot In Study

TF TAVRTF TAVR





1:1 Randomization1:1 Randomization

VS

YesYes NoNo

N = 179

TF TAVRTF TAVR AVRAVR

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

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

TA TAVRTA TAVR AVRAVR VS

VS

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

PARTNER Study DesignPARTNER Study Design

Symptomatic Severe Aortic StenosisSymptomatic Severe Aortic Stenosis



Total = 1,057 patients

2 Parallel Trials: Individually Powered

N = 699 High RiskHigh Risk


Access


Access

Transapical (TA)Transapical (TA)Transfemoral (TF)Transfemoral (TF)

1:1 Randomization1:1 Randomization1:1 Randomization1:1 Randomization

YesYes NoNo

Primary EndpointPrimary Endpoint

All-cause mortality at one yearAll-cause mortality at one year

•Analysis by intent-to-treat

•Event rates by Kaplan-Meier estimates•Crossovers permitted only when assignedtherapy unsuccessful

•All patients followed for ≥ one year

Other Important Endpoints (1)Other Important Endpoints (1)

Safety:Safety:• Neurologic events

– Prospective: Stroke and stroke plus TIA (all neuro events)

– Retrospective: Major stroke (modified Rankin Score ≥ 2 @ ≥ 30 days)

• Major vascular complications (VARC definition)

• Major bleeding (modified VARC definition)

• Repeat hospitalization

• New pacemakers and new-onset atrial fibrillation (ECG core lab)

• Procedural events (assigned therapy aborted or converted to AVR, multiple valves, etc.)

• Surgical complications (re-op for bleeding, sternal infection, etc.)

Other Important Endpoints (2)Other Important Endpoints (2)

Clinical Effectiveness and Valve Performance:Clinical Effectiveness and Valve Performance:

• NYHA symptoms

• Six-minute walk tests

• Quality-of-life measures and cost-effectiveness (core lab)

• Echocardiography assessment of valve performance (core lab)

– Peak and mean gradients– Effective orifice area– Bioprosthetic valve regurgitation (esp. para-valvular)– Other: LV ejection fraction, MR, LV mass, evidence of structural

valve deterioration

Co-Principal Investigators

Martin B. Leon, Craig R. SmithColumbia University Medical Center

Executive Committee

Martin B. Leon, Michael Mack, D. Craig Miller, Jeffrey W. Moses,Craig R. Smith, Lars G. Svensson, E. Murat Tuzcu, John G. Webb

Data & Safety Monitoring Board

Chairman: Joseph P. CarrozzaTufts University School of Medicine

Clinical Events Committee

Chairman: John L. PetersenDuke University Medical Center

Echo Core Laboratory

Chairman: Pamela C. Douglas Duke University Medical Center

Quality of Life and Cost-Effectiveness

Chairman: David J. CohenMid America Heart Institute, Kansas City

Independent BiostatisticalCore Laboratory

Stuart Pocock, Duolao WangLondon School of Hygiene andTropical Medicine

William N. Anderson

Publications Committee

Co-Chairman: Jeffrey W. MosesLars G. Svensson

Sponsor

Edwards Lifesciences: Jodi J. Akin

Study AdministrationStudy Administration

Executive Committee Executive Committee

John Webb

Murat Tuzcu

Marty Leon

Jeff MosesLars Svensson Craig Miller Michael Mack

Craig Smith

Participating Study SitesParticipating Study Sites

Intermountain Medical CenterSalt Lake City, UT

Emory UniversityAtlanta, GA

Univ. of MiamiMiami, FL

Univ. of Virginia Charlottesville, VA

St. Luke’s Hospital Kansas City, MO

Barnes-Jewish HospitalSt. Louis, MO

Medical City DallasDallas, TX

St. Paul's HospitalVancouver, Canada

Univ. of WashingtonSeattle, WA

Mayo ClinicRochester, MN

Stanford UniversityPalo Alto, CA

Hospital LavalQuebec City,

Canada

Ochsner FoundationNew Orleans, LA

Scripps ClinicLa Jolla, CA

Cedars-Sinai Medical CenterLos Angeles, CA

Cleveland ClinicCleveland, OH

Columbia UniversityCornell University New York, NY

Washington Hosp. CenterWash., DC

Univ. of Penn Phila., PA

Brigham & Women’sMass GeneralBoston, MA

Northwestern Univ.Chicago, IL

Toronto Gen. Hospital

Toronto, Canada

Evanston Hospital

Leipzig Heart Center Leipzig, Germany

n = 1,057 patients26 investigator sites22 USA, 3 Canada, 1 Germany

High-Risk Enrollment by SiteHigh-Risk Enrollment by Site

Cedars-Sinai Medical CtrLos Angeles, CAG. Fontana, R. Makkar

116

Columbia University New York City, NYM. Leon, C. Smith

97

Medical City DallasDallas, TXD. Brown, T. Dewey

95

Emory UniversityAtlanta, GAP. Block, R. Guyton

67

University of PennsylvaniaPhiladelphia, PAJ. Bavaria, H. Herrmann

52

Cleveland Clinic FoundCleveland, OHL. Svensson, M. Tuzcu

47

Washington Hospital CtrDistrict of ColumbiaP. Corso, A. Pichard

40

University of MiamiMiami, FLW. O’Neill, D. Williams

25

Barnes-Jewish HospitalSt. Louis, MOR. Damiano, J, Lasala

24

Stanford UniversityPalo Alto, CAC. Miller, A. Yeung

23

Northwestern UniversityChicago, ILC. Davidson, P. McCarthy

20

St. Paul's HospitalVancouver, BC, CanadaA. Cheung, J. Webb

19

Mass General Hospital Boston, MAI. Palacios, G. Vlahakis

15

St. Luke’s HospitalKansas City, MOK. Allen, D. Cohen

13

Universitaire de QuebecLaval, Quebec, CAD. Doyle, J. Rodes-Cabau

8

Scripps Clinic La Jolla, CAS. Brewster, P. Teirstein

7

Herzzentrum LeipzigLeipzig, GermanyF. Mohr, G. Schuler

7

Mayo ClinicRochester, MNC. Rihal, T. Sundt

6

Univ of WashingtonSeattle, WAM. Reisman, E. Verrier

5

Northshore Univ Health SysEvanston, ILJ. Alexander, T. Feldman

4

University of Virginia Charlottesville, VAI. Kron, S. Lim

3

Brigham & Women’s HospBoston, MAM. Davidson, A. Eisenhauer

2

Ochsner FoundationNew Orleans, LAE. Parrino, S. Ramee

2

Intermountain Med CenterSalt Lake City, UTK. Jones, B. Whisenant

1

Cornell University New York City, NYK. Krieger, C. Wong

1

Toronto General HospitalToronto, Ontario, CAC. Feindel, E. Horlick

0

High-Risk Enrollment by SiteHigh-Risk Enrollment by Site

Study DevicesStudy Devices

Edwards SAPIEN THV23 and 26 mm valves

RetroFlex 22 and 24 F sheaths

Ascendra 24 and 26 F sheaths

TransfemoralTransfemoral TransapicalTransapical

TAVRTAVRTransfemoral and TransapicalTransfemoral and Transapical

Inclusion CriteriaInclusion Criteria

• Severe AS: Echo-derived AVA < 0.8 cm2 (or AVA index < 0.5 cm2/m2) and mean AVG > 40 mm Hg or peak jet velocity > 4.0 m/s

• Cardiac Symptoms: NYHA Functional Class ≥ II

• High surgical risk: Predicted risk of operative mortality ≥ 15% (determined by site surgeon and cardiologist); guideline = STS score ≥ 10

Key Exclusion Criteria (1)Key Exclusion Criteria (1)

• Bicuspid or non-calcified aortic valve

• Aortic annulus diameter (echo measurement) < 18 mm or > 25 mm

• Aortic dissection or iliac-femoral dimensions or diseaseprecluding safe sheath insertion (esp. calcification)

• Severe LV dysfunction (LVEF < 20%)

• Untreated CAD requiring revascularization

• Severe AR or MR (> 3+) or prosthetic valve (any location)

Anatomic:Anatomic:

Key Exclusion Criteria (2)Key Exclusion Criteria (2)

• Serum Cr > 3.0 mg/dL or dialysis dependent

• Acute MI within 1 monthAcute MI within 1 month

• Upper GI bleed within 3 monthsUpper GI bleed within 3 months

• CVA or TIA within 6 monthsCVA or TIA within 6 months

• Any cardiac procedure, other than BAV, within 1 month Any cardiac procedure, other than BAV, within 1 month or within 6 months for DESor within 6 months for DES

• Hemodynamic instability (e.g. requiring inotropic support)Hemodynamic instability (e.g. requiring inotropic support)

Clinical:Clinical:

Statistical Analysis PlanStatistical Analysis Plan

• Primary hypothesis is non-inferiority of test (TAVR)vs. control (AVR) for all-cause mortality at 1 year

• Non-inferior if one-sided 95% upper confidence limit forthe treatment difference is < 7.5% (α =0.05)

• Primary Endpoint: All TF and TA patients– Assuming true 1-year mortality 32% after AVR and 29% after TAVR– Intended sample size = 650 patients for ≥ 85% power

• Powered Secondary Endpoint: Only TF patients– Assuming true 1-year mortality 35% after AVR and 25% after TAVR– Intended sample size = 450 patients for ≥ 85% power

Study Methodology Study Methodology

• Preliminary eligibility determined by site investigators

• Every case reviewed by web-based conference callbefore enrollment

• Randomized to TF-TAVR vs. AVR, or TA-TAVR vs. AVR, to be treated within 2 weeks

• Intent-to-treat (ITT) analysis for the primary and most secondary endpoints; defined as the time of randomization

• As-treated (AT) analysis for some procedural endpointsand for echo assessments; defined as thetime of procedural anesthesia induction

1 Year (189)Dead = 46Withdrawal = 1




Study FlowStudy Flow

AVR (248)AVR (248)

30 Days (236)Dead = 8Withdrawal = 0


Randomized = 699 patients

TF = 492TA = 207

Transfemoraln = 492

Transfemoraln = 492

TAVR (244)TAVR (244)



1 Year (73)Dead = 26Withdrawal = 0LTFU = 1




AVR (103)AVR (103)



Transapicaln = 207

Transapicaln = 207

TAVR (104)TAVR (104)



42 Patients not treated as assigned

ReasonReason TAVR (N = 348)TAVR (N = 348) AVR (N = 351)AVR (N = 351)

Died before treatment - no. (%) 2 (0.6) 5 (1.4)

Deterioration before treatment - no. (%) 1 (0.3) 5 (1.4)

Refusal - no. (%) 1 (0.3) 17 (4.8)

Withdrawal - no. (%) 0 11 (3.1)

Total – no. (%)Total – no. (%) 4 (1.1)4 (1.1) 38 (10.8)38 (10.8)

Reasons for Non-treatmentReasons for Non-treatment

ITT = 699 patients │ AT = 657 patients

NOTE: Time from randomization to treatment = TAVR 10.6 [SEM 0.7] daysvs. AVR 15.6 [SEM 1.1] days; P <0.001

CharacteristicCharacteristic TAVR (N = 348)TAVR (N = 348) AVR (N = 351)AVR (N = 351) p-valuep-value

Age (yr) 83.6 ± 6.8 84.5 ± 6.4 0.07

Male sex - % 57.8 56.7 0.82

STS Score 11.8 ± 3.3 11.7 ± 3.5 0.61

Logistic EuroSCORE 29.3 ± 16.5 29.2 ± 15.6 0.93

NYHAII - %

III or IV - % 94.3 94.0 0.79

CAD - % 74.9 76.9 0.59

Previous MI - % 26.8 30.0 0.40

Prior CV Intervention - % 72.1 71.6 0.93

Prior CABG - % 42.6 44.2 0.70

Prior PCI - % 34.0 32.5 0.68

Prior BAV - % 13.4 10.2 0.24

29.3 27.4 0.60

Patient Characteristics (1) Patient Characteristics (1)

Cerebrovascular disease - %

5.7 6.0

CharacteristicCharacteristic TAVR (N = 348)TAVR (N = 348) AVR (N = 351)AVR (N = 351) p-valuep-value

Peripheral vascular disease - % 43.0 41.6 0.76

COPD Any 43.4

Oxygen dependent 9.2 7.1 0.34

Creatinine > 2mg/dL - % 11.1 7.0 0.06

Atrial fibrillation - % 40.8 42.7 0.75

Permanent pacemaker - % 20.0 21.9 0.58

Pulmonary hypertension - % 42.4 36.4 0.15

Frailty - % 15.6 17.6 0.58

Porcelain aorta - % 0.6 1.1 0.69

Chest wall radiation - % 0.9 0.9 1.00

Liver disease - % 2.0 2.6 0.80

Patient Characteristics (2) Patient Characteristics (2)

43.0 0.94

Baseline Echocardiography Baseline Echocardiography

Echo FindingsEcho Findings TAVR (N = 348)TAVR (N = 348) AVR (N = 351)AVR (N = 351) p-valuep-value

AVA - cm2 0.7 ± 0.2 0.6 ± 0.2 0.13

AVG - mm Hg 42.7 ± 14.6 43.5 ± 14.3 0.45

Mean LVEF - % 52.5 ± 13.5 53.3 ± 12.8 0.45

Moderate or severe MR - % 19.8 21.3 0.63

Anesthesia time - min 330

Total procedure time - min 230

Aborted procedure - no. (%) 0

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

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

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

Aortic dissection - no. (%) 3 (0.9)

Median ICU stay (days) 5.0

Anesthesia time - min 236

Total procedure time - min 133

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

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

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

Aortic perforation - no. (%) 0

Aortic dissection - no. (%) 3 (0.9)

Median ICU stay (days) 3.0

Procedural Outcomes - TAVR vs AVRProcedural Outcomes - TAVR vs AVR

*Converted to transapical TAVR due to porcelain aorta

AVR TAVR

3 failed access2 new TEE findings

2 died

3 failed access2 new TEE findings

2 diedAborted procedure - no. (%)Aborted procedure - no. (%)

Sternal wound infection - no. (%) 7 (2.0)

Total cross clamp time - min 74

Pump time - min 105

Access site infection - no. (%) 7 (2.0)

Fluoroscopy time - min 31

Converted to AVR - no. (%) 9 (2.6)

Multiple (≥2) valves - no. (%) 7 (2.0)

Valve embolization - no. (%) 9 (2.6)

Procedural Outcomes - TAVR vs AVRProcedural Outcomes - TAVR vs AVR

*Converted to transapical TAVR due to porcelain aorta

AVR TAVR

5 valve embolization3 annulus size on TEE

1 large sigmoid septum

5 valve embolization3 annulus size on TEE

1 large sigmoid septumConverted to AVR - no. (%)Converted to AVR - no. (%)

5 converted to AVR2 valve-in-valve

2 not treated

5 converted to AVR2 valve-in-valve

2 not treatedValve embolization - no. (%)Valve embolization - no. (%)

0

0.1

0.2

0.3

0.4

0.5

0 6 12 18 24

TAVR

AVR

Months

348 298 260 147 67

351 252 236 139 65

No. at Risk

TAVR

AVR

26.8

24.2

Primary Endpoint:Primary Endpoint:All-Cause Mortality at 1 YearAll-Cause Mortality at 1 Year

HR [95% CI] =0.93 [0.71, 1.22]

P (log rank) = 0.62

Primary Endpoint:Primary Endpoint:All-Cause Mortality at 1 YearAll-Cause Mortality at 1 Year

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 %

AVR (N = 351)

26.8%

AVR (N = 351)

26.8%

TAVR (N = 348)

24.2%

TAVR (N = 348)

24.2%

Difference -2.6%

Upper 1-sided Upper 1-sided 95% CI95% CI3.0%3.0%

Difference -2.6%


Primary Non-Inferiority Endpoint MetPrimary Non-Inferiority Endpoint Met

Non-inferiority

P value

= 0.001

Non-inferiority

P value

= 0.001

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

All-Cause MortalityAll-Cause MortalityTransfemoral (N=492)Transfemoral (N=492)

Months

244 215 188 119 59

248 180 168 109 56

No. at Risk

TAVR

AVR

26.4

22.2

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

P (log rank) = 0.25

Powered Secondary Endpoint (ITT):TF All-Cause Mortality at 1 Year

7.0-4.0 -1.0 0.0 6.03.0 4.0 5.0-5.0


1.0 2.0

Non-inferior


Secondary TF Non-Inferiority Endpoint MetSecondary TF Non-Inferiority Endpoint Met

8.0 %

Difference -4.2%


Difference -4.2%


Non-inferiority

P value

= 0.002

Non-inferiority

P value

= 0.002

-2.0-3.0

AVR (N = 244)

26.4%

AVR (N = 244)

26.4%

TAVR (N = 248)

22.2%

TAVR (N = 248)

22.2%

104 83 72 28 8

103 72 68 30 9

29.0

27.9

TAVR

AVR

MonthsNo. at Risk

All-Cause MortalityAll-Cause MortalityTransapical (N=207)Transapical (N=207)

HR [95% CI] =1.22 [0.75, 1.98]

P (log rank) = 0.41

Surgical AVR OutcomesSurgical AVR Outcomes

• Using an established predictive risk model (STS), the expected (“E”) 30-day mortality after AVR was 11.8%.

• The observed (“O”) 30-day mortality in the as-treated AVR control group was 8.0%.

• O:E = 0.68 indicates better than predicted surgical outcomes in the control AVR patients.

• There were no significant site or surgeon differences.

All-Cause Mortality at 30 DaysAll-Cause Mortality at 30 DaysAll Patients

no. of patients ( %)TF Patients

no. of patients ( %)TA Patients

no. 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

All-Cause Mortality at 1 YearAll-Cause Mortality at 1 YearAll Patients

no. of patients ( %)TF Patients

no. of patients ( %)TA Patients

no. of patients ( %)

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

ITT 84 (24.2) 89 (26.8) 0.44 54 (22.2) 62 (26.4) 0.29 30 (29.0) 27 (27.9) 0.85

AT 81 (23.7) 78 (25.2) 0.64 51 (21.3) 55 (25.2) 0.33 30 (29.1) 23 (25.3) 0.55

All-Cause Mortality at 30 Days and 1 Year All-Cause Mortality at 30 Days and 1 Year ITT and ATT by SubgroupITT and ATT by Subgroup

30 Days 1 Year

OutcomeOutcome TAVRTAVR(N = 348)(N = 348)

AVRAVR(N = 351)(N = 351) p-valuep-value TAVRTAVR

(N = 348)(N = 348)AVRAVR

(N = 351)(N = 351) p-valuep-value

All mortality – no. (%)All mortality – no. (%) 12 (3.4) 22 (6.5) 0.07 84 (24.2) 89 (26.8) 0.44

Cardiac mortality – no. (%) 11 (3.2) 10 (3.0) 0.90 47 (14.3) 40 (13.0) 0.63

Rehospitalization – no. (%) 15 (4.4) 12 (3.7) 0.64 58 (18.2) 45 (15.5) 0.38

Death or rehosp – no. (%)Death or rehosp – no. (%) 25 (7.2) 33 (9.7) 0.24 120 (34.6) 119 (35.9) 0.73

MI – no. (%) 0 2 (0.6) 0.16 1 (0.4) 2 (0.6) 0.69

Acute kidney inj* – no. (%) 10 (2.9) 10 (3.0) 0.95 18 (5.4) 20 (6.5) 0.56

Clinical Outcomes at 30 Days and 1 Year Clinical Outcomes at 30 Days and 1 Year All Patients (N=699)All Patients (N=699)

* Renal replacement therapy

30 Days 1 Year


AVRAVR(N = 351)(N = 351) p-valuep-value TAVRTAVR

(N = 348)(N = 348)AVRAVR

(N = 351)(N = 351) p-valuep-value

Vascular complications

All – no. (%) 59 (17.0)59 (17.0) 13 (3.8)13 (3.8) <0.01<0.01 62 (18.0)62 (18.0) 16 (4.8)16 (4.8) <0.01<0.01

Major – no. (%)Major – no. (%) 38 (11.0)38 (11.0) 11 (3.2)11 (3.2) <0.01<0.01 39 (11.3)39 (11.3) 12 (3.5)12 (3.5) <0.01<0.01

Major bleeding – no. (%)Major bleeding – no. (%) 32 (9.3)32 (9.3) 67 (19.5)67 (19.5) <0.01<0.01 49 (14.7)49 (14.7) 85 (25.7)85 (25.7) <0.01<0.01

Endocarditis – no. (%) 0 (0.0)0 (0.0) 1 (0.3)1 (0.3) 0.320.32 2 (0.6)2 (0.6) 3 (1.0)3 (1.0) 0.630.63

New AF – no. (%)New AF – no. (%) 30 (8.6)30 (8.6) 56 (16.0)56 (16.0) < 0.01< 0.01 42 (12.1)42 (12.1) 60 (17.1)60 (17.1) 0.070.07

New PM – no. (%)New PM – no. (%) 13 (3.8)13 (3.8) 12 (3.6)12 (3.6) 0.890.89 19 (5.7)19 (5.7) 16 (5.0)16 (5.0) 0.680.68

Clinical Outcomes at 30 Days and 1 Year Clinical Outcomes at 30 Days and 1 Year All Patients (N=699)All Patients (N=699)

30 Days 1 Year


AVRAVR(N = 351)(N = 351)

TAVRTAVR(N = 348)(N = 348)

AVRAVR(N = 351)(N = 351)

All Stroke or TIA – no. (%)All Stroke or TIA – no. (%) 19 (5.5)19 (5.5) 8 (2.4)8 (2.4) 0.040.04 27 (8.3)27 (8.3) 13 (4.3)13 (4.3) 0.040.04

TIA – no. (%) 3 (0.9) 1 (0.3) 0.33 7 (2.3) 4 (1.5) 0.47

All Stroke – no. (%) 16 (4.6) 8 (2.4) 0.12 20 (6.0) 10 (3.2) 0.08

Major Stroke – no. (%)Major Stroke – no. (%) 13 (3.8)13 (3.8) 7 (2.1)7 (2.1) 0.200.20 17 (5.1)17 (5.1) 8 (2.4)8 (2.4) 0.070.07

Minor Stroke – no. (%) 3 (0.9) 1 (0.3) 0.34 3 (0.9) 2 (0.7) 0.84

Death/maj stroke – no. (%)Death/maj stroke – no. (%) 24 (6.9)24 (6.9) 28 (8.2)28 (8.2) 0.520.52 92 (26.5)92 (26.5) 93 (28.0)93 (28.0) 0.680.68

Neurological Events at 30 Days and 1 Year Neurological Events at 30 Days and 1 Year All Patients (N=699)All Patients (N=699)

p-valuep-value p-valuep-value

Months

348 289 252 143 65

351 247 232 138 63

No. at Risk

TAVR

AVR

28.0

26.5

HR [95% CI] =0.95 [0.73, 1.23]

P (log rank) = 0.70

All-Cause Mortality or StrokeAll-Cause Mortality or StrokeAll Patients (N=699)All Patients (N=699)

NYHA Functional Class NYHA Functional Class

Baseline 1 Year6 Months30 Days

Pat

ient

s S

urvi

ving

, %

I II III IV

P = 1.00 P < 0.001 P = 0.05 P = 0.75

Six-Minute Walk TestSix-Minute Walk TestAll Patients (N=699)All Patients (N=699)

Med

ian

Dis

tanc

e, m

eter

s

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

SubgroupSubgroupTAVR (%)TAVR (%)

n=348n=348AVR (%) AVR (%)

n=351n=351RR RR

(95% CI) (95% CI) RR RR

(95% CI)(95% CI)P-value for P-value for

interactioninteraction

Overall 24.1 25.4 0.95(0.73-1.23)

Age<85>85

21.627.0

24.926.1

0.87(0.60-1.27)1.03(0.72-1.47)

0.52

SexMaleFemale

28.418.4

24.227.2

1.17(0.84-1.63)1.17(0.84-1.63)

0.045

BMI<26>26

27.321.0

27.423.8

0.68(0.44-1.04)0.99(0.71-1.40)

0.66

STS score<11>11

19.928.1

21.729.3

0.88(0.59-1.31)0.92(0.61-1.38)

0.87

LV ejection fraction

<55>55

26.222.4

27.722.1

0.96(0.69-1.34)1.01(0.68-1.50)

0.80

Subgroup Analyses of Treatment EffectSubgroup Analyses of Treatment Effect All-Cause Mortality at 1 YearAll-Cause Mortality at 1 Year

TAVR betterTAVR better AVR betterAVR better

0.5 1 2

SubgroupSubgroupTAVR (%)TAVR (%)

n=348n=348AVR (%) AVR (%)

n=351n=351RR RR

(95% CI) (95% CI) RR RR

(95% CI)(95% CI)P-value for P-value for

interactioninteraction

Pulmonary hypertension

NoYes

21.327.4

21.729.9

0.98(0.64-1.50)0.92(0.66-1.28)

0.80

Mitral regurgitation

NoYes

24.624.2

22.135.2

1.11(0.82-1.52)0.69(0.41-1.17)

0.12

Prior CABGNoYes

22.225.9

30.719.1

0.72(0.52-1.01)1.35(0.88-2.08)

0.02

Peripheral vasc disease

NoYes

22.426.4

25.125.4

0.89(0.63-1.27)1.04(0.70-1.54)

0.57

Cohort TA TF

28.822.1

26.225.0

1.10(0.71-1.71)0.89(0.64-1.22)

0.43

TAVR betterTAVR better AVR betterAVR better

0.5 1 2

Subgroup Analyses of Treatment EffectSubgroup Analyses of Treatment Effect All-Cause Mortality at 1 YearAll-Cause Mortality at 1 Year

Mean Gradient - AVR

Mean Gradient - TAVR

Peak Gradient - AVR

Peak Gradient - TAVR

Mea

n an

d P

eak

Gra

dien

tA

s-T

reat

ed T

rial A

rms

(mm

Hg)

50

40

30

20

60

70

10

0

80

Baseline 30 Days 6 Months 1 YearTAVR

n = 327AVR

n = 301TAVR

n = 287AVR

n = 231TAVR

n = 246AVR

n = 170TAVR

n = 227AVR

n = 159

Echo FindingsEcho FindingsAortic Valve GradientsAortic Valve Gradients

Echo FindingsHemodynamic Assessments

30 Days 1 Year

Finding TAVR AVR TAVR AVR

AVG – mmHg 9.9 ± 4.8 10.8 ± 5.0 0.04 10.2 ± 4.3 11.5 ± 5.4 0.008

AVA - cm2 1.7 ± 0.5 1.5 ± 0.4 0.001 1.6 ± 0.5 1.4 ± 0.5 0.002

LVEF - % 55.5 ± 11.4 56.0 ± 11.4 0.63 56.6 ± 10.5 57.1 ± 10.3 0.64

p-value p-value

Paravalvular Aortic RegurgitationParavalvular Aortic Regurgitation

P < 0.001 P < 0.001 P < 0.001

1 Year6 Months30 Days

Pat

ient

s, %

None Trace Mild Moderate Severe

Study LimitationsStudy Limitations

• 8% of the control (AVR) group withdrew or refused assignedtherapy

• 5% of patients randomized to TAVR did not receiveassigned therapy (procedure aborted or converted to AVR)

• Significantly longer interval between randomization andtreatment in controls (AVR)

• An early version large TAVR delivery system was used

• Most sites had no previous TAVR experience - learningcurve impact inherent in TAVR, but not in AVR

• Insufficient statistical power to compare TA to either AVRor TF

• Long-term follow-up not available to assess TAVR durability

Conclusions (1)Conclusions (1)

• The primary endpoint of the trial was met:– In patients with aortic stenosis at high risk for operation, TAVR

was non-inferior to AVR for all-cause mortality at 1 year (24.2% vs. 26.8%, p=0.001 for non inferiority)

– Transfemoral TAVR subgroup was also non-inferior toAVR (p=0.002 for non-inferiority)

• Death at 30 days was lower than expected in botharms of the trial:

– TAVR mortality (3.4%) was the lowest reported in any series, despite an early generation device and limited previous operator experience

– AVR mortality (6.5%) was lower than the expected operative mortality (11.8%)


• Both TAVR and AVR were associated with important but different peri-procedural hazards:

– Major strokes at 30 days (3.8 vs. 2.1%, p=0.20) and one year (5.1% vs. 2.4%, p=0.07) and major vascular complications were more frequent with TAVR (11.0% vs. 3.2%, p<0.001)

– Major bleeding (9.3% vs. 19.5%, p<0.001) and new onset atrial fibrillation (8.6% vs. 16.0%, p<0.001) were more frequent with AVR

• TAVR and AVR are both acceptable therapies in these high-risk patients; differing peri-procedural hazards should influence case-based decision-making


• Symptom improvement (NYHA class and 6-min walkdistance) favored TAVR at 30 days and was similar to AVR at one year

• Echo findings indicate:– Small hemodynamic benefit with TAVR vs. AVR at 1 year

(mean gradient p=0.008, AVA p=0.002)– Increased para-valvular regurgitation associated with

TAVR (p<0.001)

• Preliminary subgroup analyses should be interpretedcautiously:

– Possible TAVR benefit in women and patients without prior CABG

ImplicationsImplications

• A multidisciplinary valve team approach benefits patients and is recommended for all future valve centers.

• TAVR is already the standard-of-care for inoperable patients with severe aortic stenosis. These results indicate that TAVR is an acceptable alternative to AVR in selected high-risk operable patients.

• Future randomized studies should focus on lower risk patients who are candidates for operation.

Back-up SlidesBack-up Slides

PARTNER Comparison of OutcomesPARTNER Comparison of OutcomesHigh-Risk vs. Inoperable PatientsHigh-Risk vs. Inoperable Patients

Per

Cen

t (%

)

5.0

11.0

TAVR AVR

ComplicationComplication WithWith WithoutWithout WithWith WithoutWithout

Stroke or TIA

All Patients – no. 31 313 16 297

Died Died ≤ 30 days – no. (≤ 30 days – no. (%)%) 2 (6.5)2 (6.5) 16 (5.1)16 (5.1) 1 (6.3)1 (6.3) 24 (8.1)24 (8.1)

Died ≤ 1 year – no. (%)≤ 1 year – no. (%) 10 (32.3) 71 (22.8) 3 (18.8) 75 (25.6)

Major Stroke


Died Died ≤ 30 days – no. (≤ 30 days – no. (%)%) 2 (11.1) 16 (4.9) 1 (9.1) 24 (8.0)


Neurological Events and Mortality Neurological Events and Mortality at 30 Days and 1 Year (as treated)at 30 Days and 1 Year (as treated)

TAVR AVR

ComplicationComplication WithWith WithoutWithout WithWith WithoutWithout

Major Vascular


Died Died ≤ 30 days – no. (≤ 30 days – no. (%)%) 6 (15.8)6 (15.8) 12 (3.9)12 (3.9) 2 (19.2)2 (19.2) 23 (7.6)23 (7.6)


Major Bleeding


Died Died ≤ 30 days – no. (≤ 30 days – no. (%)%) 2 (3.8) 16 (5.5) 15 (17.1) 10 (4.5)


Vascular/Bleeding Events and Mortality Vascular/Bleeding Events and Mortality at 30 Days and 1 Year (as treated)at 30 Days and 1 Year (as treated)

All-Cause Mortality (As Treated TAVR Trial Arm)All-Cause Mortality (As Treated TAVR Trial Arm)Stratified by Major StrokeStratified by Major Stroke

Months

All-Cause Mortality (As Treated TAVR Trial Arm)All-Cause Mortality (As Treated TAVR Trial Arm)Stratified by Major Vascular EventStratified by Major Vascular Event

Months

All-Cause Mortality (As Treated TAVR Trial Arm)All-Cause Mortality (As Treated TAVR Trial Arm)Stratified by Major BleedStratified by Major Bleed

Months

All-Cause Mortality (As Treated AVR Trial Arm)All-Cause Mortality (As Treated AVR Trial Arm)Stratified by Major StrokeStratified by Major Stroke

Months

All-Cause Mortality (As Treated AVR Trial Arm)All-Cause Mortality (As Treated AVR Trial Arm)Stratified by Major BleedStratified by Major Bleed

Months

All-Cause Mortality (As Treated AVR Trial Arm)All-Cause Mortality (As Treated AVR Trial Arm)Stratified by New Atrial fibrillationStratified by New Atrial fibrillation

Months

All-Cause Mortality All-Cause Mortality (As Treated)(As Treated)Pooled Implant Approaches (N= 657)Pooled Implant Approaches (N= 657)

Months

344 291 258 139 64

313 243 226 128 60

No. at Risk

TAVR

AVR

25.2

23.7

HR [95% CI] =1.02 [0.77, 1.36]

P (log rank) = 0.88

Primary Endpoint: (As Treated)Primary Endpoint: (As Treated)All-Cause Mortality at 1 YearAll-Cause Mortality at 1 Year

7.0-2.0 -1.0 0.0 6.03.0 4.0 5.0-3.0


1.0 2.0

Non-inferior


Primary Non-Inferiority Endpoint MetPrimary Non-Inferiority Endpoint Met

8.0 %

Difference -1.6%


Difference -1.6%


Non-inferiority

P value

= 0.004

Non-inferiority

P value

= 0.004

AVR (N = 313)

25.2%

AVR (N = 313)

25.2%

TAVR (N = 344)

23.6%

TAVR (N = 344)

23.6%

All-Cause Mortality All-Cause Mortality (As Treated)(As Treated)Transfemoral (N=461)Transfemoral (N=461)

Months

240 209 186 112 58

221 172 161 100 53

No. at Risk

TAVR

AVR

25.2

21.3

HR [95% CI] =0.90 [0.64, 1.26]

P (log rank) = 0.53

Powered Secondary Endpoint (AT):Powered Secondary Endpoint (AT):TF All-Cause Mortality at 1 YearTF All-Cause Mortality at 1 Year

7.0-4.0 -1.0 0.0 6.03.0 4.0 5.0-5.0


1.0 2.0

Non-inferior


Secondary TF Non-Inferiority Endpoint MetSecondary TF Non-Inferiority Endpoint Met

8.0 %

Difference -3.9%


Difference -3.9%


Non-inferiority

P value

= 0.002

Non-inferiority

P value

= 0.002

-2.0-3.0

AVR (N = 221)

25.2%

AVR (N = 221)

25.2%

TAVR (N =240 )

21.3%

TAVR (N =240 )

21.3%

All-Cause Mortality All-Cause Mortality (As Treated)(As Treated)Transapical (N=196)Transapical (N=196)

Months

104 82 72 27 6

92 71 65 28 7

No. at Risk

TAVR

AVR

25.3

29.1

HR [95% CI] =1.36 [0.82, 2.26]

P (log rank) = 0.23

All-Cause Mortality All-Cause Mortality Stratified by ITT Trial Arm and Patient GenderStratified by ITT Trial Arm and Patient Gender

All-Cause Mortality All-Cause Mortality Stratified by ITT Trial Arm and Prior CABGStratified by ITT Trial Arm and Prior CABG

All-Cause Mortality All-Cause Mortality Stratified by ITT trial arm and Moderate/Severe MRStratified by ITT trial arm and Moderate/Severe MR

Echo FindingsEcho FindingsValvular RegurgitationValvular Regurgitation

30 Days 1 Year

Finding – no. (%)Finding – no. (%) TAVRTAVR AVRAVR TAVRTAVR AVRAVR

Transvalv. Regurg.

Mod/Severe3 (1.0) 2 (0.9) <.0001 2 (0.9) 0 (0.0) <.0001

Paravalv. Regurg.Paravalv. Regurg.

Mod/SevereMod/Severe35 (12.2)35 (12.2) 2 (0.9)2 (0.9) <.0001<.0001 15 (6.8)15 (6.8) 3 (1.9)3 (1.9) <.0001<.0001

All Regurg.

Mod/Severe21 (7.7) 4 (1.7) <0.001 12 (5.5) 3 (1.9) <0.001


Echo FindingsEcho FindingsParavalvular RegurgitationParavalvular Regurgitation

30 Days 1 Year

Finding – no. (%)Finding – no. (%) TAVRTAVR AVRAVR TAVRTAVR AVRAVR

None 65 (22.6) 168 (73.7) <.0001 73 (32.9) 123 (77.8) <.0001

Trace/Mild Trace/Mild 187 (65.2)187 (65.2) 58 (25.4)58 (25.4) <.0001<.0001 134 (60.4)134 (60.4) 32 (20.3)32 (20.3) <.0001<.0001

Mod/Severe 35 (12.2)35 (12.2) 2 (0.9)2 (0.9) <.0001<.0001 15 (6.8)15 (6.8) 3 (1.9)3 (1.9) <.0001<.0001


AVR

TAVR

Val

ve A

rea,

cm

2

Aortic Valve AreaAortic Valve AreaAs Treated Trial ArmsAs Treated Trial Arms

TAVRn = 319

AVRn = 297

TAVRn = 279

AVRn = 228

TAVRn = 235

AVRn = 165

TAVRn = 219

AVRn = 155

craig r. smith, md on behalf of the partner trial investigators

Documents

surgical avr

symptomatic aortic stenosis

operable patients

high risk patients

partner trialacc

highrisk avr candidate3

total patients screenedtotal

craig miller