craig r. smith, md on behalf of the partner trial investigators
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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 for PARTNER at ACC April 3, 2011
Background
• 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.
Purpose
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 Risk Inoperable
PARTNER Study Design
Symptomatic Severe Aortic Stenosis
ASSESSMENT: High-Risk AVR Candidate3,105 Total Patients Screened
Total = 1,057 patients2 Parallel Trials:
Individually Powered
StandardTherapy
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 N = 179
Inoperable PARTNER CohortPrimary Endpoint: All-Cause Mortality
Numbers at Risk TAVI 179 138 122 67 26 Standard Rx 179 121 83 41 12
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 = 358Inoperable
StandardTherapy
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 VS
VS
N = 248 N = 104 N = 103N = 244
PARTNER Study Design
Symptomatic Severe Aortic Stenosis
ASSESSMENT: High-Risk AVR Candidate3,105 Total Patients Screened
Total = 1,057 patients2 Parallel Trials:
Individually Powered
N = 699 High Risk
ASSESSMENT: Transfemoral
Access
Transapical (TA)Transfemoral (TF)
1:1 Randomization1:1 Randomization
Yes No
Primary Endpoint
All-cause mortality at one year
• Analysis by intent-to-treat
• Event rates by Kaplan-Meier estimates• Crossovers permitted only when assigned
therapy unsuccessful
• All patients followed for ≥ one year
Other Important Endpoints (1)
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)
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 InvestigatorsMartin B. Leon, Craig R. SmithColumbia University Medical Center
Executive CommitteeMartin 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 BoardChairman: Joseph P. CarrozzaTufts University School of Medicine
Clinical Events CommitteeChairman: John L. PetersenDuke University Medical Center
Echo Core LaboratoryChairman: Pamela C. Douglas Duke University Medical Center
Quality of Life and Cost-EffectivenessChairman: David J. CohenMid America Heart Institute, Kansas City
Independent BiostatisticalCore Laboratory
Stuart Pocock, Duolao WangLondon School of Hygiene andTropical Medicine
William N. Anderson
Publications CommitteeCo-Chairman: Jeffrey W. MosesLars G. Svensson
SponsorEdwards Lifesciences: Jodi J. Akin
Study Administration
Executive Committee
John Webb
Murat Tuzcu
Marty Leon
Jeff MosesLars Svensson Craig Miller Michael Mack
Craig Smith
Participating 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 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 Site
Study Devices
Edwards SAPIEN THV23 and 26 mm valves
RetroFlex 22 and 24 F sheaths
Ascendra 24 and 26 F sheaths
Transfemoral Transapical
TAVRTransfemoral and Transapical
Inclusion 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)
• 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:
Key Exclusion Criteria (2)
• Serum Cr > 3.0 mg/dL or dialysis dependent
• Acute MI within 1 month
• Upper GI bleed within 3 months
• CVA or TIA within 6 months
• Any cardiac procedure, other than BAV, within 1 month or within 6 months for DES
• Hemodynamic instability (e.g. requiring inotropic support)
Clinical:
Statistical 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
• 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
1 Year (168)Dead = 47Withdrawal = 8
Study Flow
AVR (248)
30 Days (236)Dead = 8Withdrawal = 0
Randomized = 699 patients
TF = 492TA = 207
Transfemoraln = 492
TAVR (244)
30 Days (223)Dead = 15Withdrawal = 10
1 Year (73)Dead = 26Withdrawal = 0LTFU = 1
1 Year (68)Dead = 20Withdrawal = 3LTFU = 1
AVR (103)
30 Days (100)Dead = 4Withdrawal = 0
Transapicaln = 207
TAVR (104)
30 Days (92)Dead = 7Withdrawal = 4
42 Patients not treated as assigned
Reason TAVR (N = 348) 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. (%) 4 (1.1) 38 (10.8)
Reasons 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
Characteristic TAVR (N = 348) AVR (N = 351) p-value
Age (yr) 83.6 ± 6.8 84.5 ± 6.4 0.07Male sex - % 57.8 56.7 0.82STS Score 11.8 ± 3.3 11.7 ± 3.5 0.61Logistic EuroSCORE 29.3 ± 16.5 29.2 ± 15.6 0.93NYHA
II - %III or IV - % 94.3 94.0 0.79
CAD - % 74.9 76.9 0.59Previous MI - % 26.8 30.0 0.40Prior CV Intervention - % 72.1 71.6 0.93
Prior CABG - % 42.6 44.2 0.70Prior PCI - % 34.0 32.5 0.68Prior BAV - % 13.4 10.2 0.24
29.3 27.4 0.60
Patient Characteristics (1)
Cerebrovascular disease - %
5.7 6.0
Characteristic TAVR (N = 348) AVR (N = 351) p-value
Peripheral vascular disease - % 43.0 41.6 0.76COPD 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)
43.0 0.94
Baseline Echocardiography
Echo Findings TAVR (N = 348) AVR (N = 351) p-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 AVR
*Converted to transapical TAVR due to porcelain aorta
AVR TAVR
3 failed access2 new TEE findings
2 diedAborted 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 AVR
*Converted to transapical TAVR due to porcelain aorta
AVR TAVR
5 valve embolization3 annulus size on TEE
1 large sigmoid septumConverted to AVR - no. (%)
5 converted to AVR2 valve-in-valve
2 not treatedValve embolization - no. (%)
0
0.1
0.2
0.3
0.4
0.5
0 6 12 18 24
TAVRAVR
Months
348 298 260 147 67
351 252 236 139 65
No. at Risk
TAVR
AVR
26.8
24.2
Primary Endpoint:All-Cause Mortality at 1 Year
HR [95% CI] =0.93 [0.71, 1.22]
P (log rank) = 0.62
Primary Endpoint:All-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%
TAVR (N = 348)
24.2%
Difference -2.6%
Upper 1-sided 95% CI3.0%
Primary Non-Inferiority Endpoint Met
Non-inferiority
P value= 0.001
Zone of non-inferiority pre-specified margin = 7.5%
0 6 12 18 240
0.1
0.2
0.3
0.4
0.5TAVRAVR
All-Cause MortalityTransfemoral (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
Zone of non-inferiority pre-specified margin = 7.5%
1.0 2.0
Non-inferior
Upper one-sided 95% CI
Secondary TF Non-Inferiority Endpoint Met
8.0 %
Difference -4.2%
Upper 1-sided 95% CI2.3%
Non-inferiority
P value= 0.002
-2.0-3.0
AVR (N = 244)
26.4%
TAVR (N = 248)
22.2%
0 6 12 18 240
0.1
0.2
0.3
0.4
0.5TAVRAVR
104 83 72 28 8
103 72 68 30 9
29.0
27.9
TAVR
AVR
MonthsNo. at Risk
All-Cause MortalityTransapical (N=207)
HR [95% CI] =1.22 [0.75, 1.98]
P (log rank) = 0.41
Surgical 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 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 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 ITT and ATT by Subgroup
30 Days 1 Year
Outcome TAVR(N = 348)
AVR(N = 351) p-value TAVR
(N = 348)AVR
(N = 351) p-value
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. (%) 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 All Patients (N=699)
* Renal replacement therapy
30 Days 1 Year
Outcome TAVR(N = 348)
AVR(N = 351) p-value TAVR
(N = 348)AVR
(N = 351) p-value
Vascular complications
All – no. (%) 59 (17.0) 13 (3.8) <0.01 62 (18.0) 16 (4.8) <0.01
Major – no. (%) 38 (11.0) 11 (3.2) <0.01 39 (11.3) 12 (3.5) <0.01
Major bleeding – no. (%) 32 (9.3) 67 (19.5) <0.01 49 (14.7) 85 (25.7) <0.01
Endocarditis – no. (%) 0 (0.0) 1 (0.3) 0.32 2 (0.6) 3 (1.0) 0.63
New AF – no. (%) 30 (8.6) 56 (16.0) < 0.01 42 (12.1) 60 (17.1) 0.07
New PM – no. (%) 13 (3.8) 12 (3.6) 0.89 19 (5.7) 16 (5.0) 0.68
Clinical Outcomes at 30 Days and 1 Year All Patients (N=699)
30 Days 1 Year
Outcome TAVR(N = 348)
AVR(N = 351)
TAVR(N = 348)
AVR(N = 351)
All Stroke or TIA – no. (%) 19 (5.5) 8 (2.4) 0.04 27 (8.3) 13 (4.3) 0.04
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. (%) 13 (3.8) 7 (2.1) 0.20 17 (5.1) 8 (2.4) 0.07
Minor Stroke – no. (%) 3 (0.9) 1 (0.3) 0.34 3 (0.9) 2 (0.7) 0.84
Death/maj stroke – no. (%) 24 (6.9) 28 (8.2) 0.52 92 (26.5) 93 (28.0) 0.68
Neurological Events at 30 Days and 1 Year All Patients (N=699)
p-value p-value
0 6 12 18 240
0.1
0.2
0.3
0.4
0.5TAVRAVR
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 Patients (N=699)
NYHA Functional Class
TAVR AVR TAVR AVR TAVR AVR TAVR AVR0
20
40
60
80
100
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 TestAll Patients (N=699)
Baseline 30 Days 6 Months 1 Year0
50
100
150
200
71 75
192
175
75
128
165152
AVR TAVR
Med
ian
Dis
tanc
e, m
eter
sP = 0.73 P = 0.002 P = 0.33 P = 0.76
SubgroupTAVR (%)
n=348AVR (%)
n=351RR
(95% CI) RR
(95% CI)P-value for
interaction
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 Effect All-Cause Mortality at 1 Year
TAVR better AVR better0.5 1 2
SubgroupTAVR (%)
n=348AVR (%)
n=351RR
(95% CI) RR
(95% CI)P-value for
interactionPulmonary 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 22.4
26.425.125.4
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 better AVR better0.5 1 2
Subgroup Analyses of Treatment Effect All-Cause Mortality at 1 Year
Mean Gradient - AVRMean Gradient - TAVR
Peak Gradient - AVRPeak Gradient - TAVR
Mea
n an
d P
eak
Gra
dien
tA
s-Tr
eate
d Tr
ial 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 FindingsAortic 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 Regurgitation
TAVR AVR TAVR AVR TAVR AVR0
20
40
60
80
100P < 0.001 P < 0.001 P < 0.001
1 Year6 Months30 Days
Pat
ient
s, %
None Trace Mild Moderate Severe
Study 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)
• 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%)
Conclusions (2)
• 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
Conclusions (3)
• 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
Implications
• 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 Slides
PARTNER Comparison of OutcomesHigh-Risk vs. Inoperable Patients
Mortality (TF) Maj Stroke Maj Vascular Maj Bleed New PM PVL (1 yr)0
5
10
15
20
25
6.4
16.2 16.8
3.4
11.8
3.7 3.8
9.3
3.8
6.8
Inoperable High-Risk
Per
Cen
t (%
)
5.0
11.0
TAVR AVR
Complication With Without With Without
Stroke or TIA
All Patients – no. 31 313 16 297
Died ≤ 30 days – no. (%) 2 (6.5) 16 (5.1) 1 (6.3) 24 (8.1)
Died ≤ 1 year – no. (%) 10 (32.3) 71 (22.8) 3 (18.8) 75 (25.6)
Major Stroke
All Patients – no. 18 326 11 302
Died ≤ 30 days – no. (%) 2 (11.1) 16 (4.9) 1 (9.1) 24 (8.0)
Died ≤ 1 year – no. (%) 9 (50.0) 72 (22.2) 3 (27.3) 75 (25.1)
Neurological Events and Mortality at 30 Days and 1 Year (as treated)
TAVR AVR
Complication With Without With Without
Major Vascular
All Patients – no. 38 306 11 302
Died ≤ 30 days – no. (%) 6 (15.8) 12 (3.9) 2 (19.2) 23 (7.6)
Died ≤ 1 year – no. (%) 14 (37.3) 67 (22.0) 5 (49.5) 73 (24.4)
Major Bleeding
All Patients – no. 52 292 88 225
Died ≤ 30 days – no. (%) 2 (3.8) 16 (5.5) 15 (17.1) 10 (4.5)
Died ≤ 1 year – no. (%) 16 (31.1) 65 (22.3) 36 (41.3) 42 (18.9)
Vascular/Bleeding Events and Mortality at 30 Days and 1 Year (as treated)
All-Cause Mortality (As Treated TAVR Trial Arm)Stratified by Major Stroke
Months
0 6 12 18 240
0.10.2
0.30.40.50.60.7
0.80.9
1No Event
Event
All-Cause Mortality (As Treated TAVR Trial Arm)Stratified by Major Vascular Event
Months
0 6 12 18 240
0.10.20.30.40.50.60.7
0.80.9
1No Event
Event
All-Cause Mortality (As Treated TAVR Trial Arm)Stratified by Major Bleed
Months
0 6 12 18 240
0.10.20.30.40.50.60.7
0.80.9
1No Event
Event
All-Cause Mortality (As Treated AVR Trial Arm)Stratified by Major Stroke
Months
0 6 12 18 240
0.10.20.30.40.50.60.7
0.80.9
1No Event
Event
All-Cause Mortality (As Treated AVR Trial Arm)Stratified by Major Bleed
Months
0 6 12 18 240
0.10.20.30.40.50.60.7
0.80.9
1No Event
Event
All-Cause Mortality (As Treated AVR Trial Arm)Stratified by New Atrial fibrillation
Months
0 6 12 18 240
0.10.20.30.40.50.60.7
0.80.9
1No Event
Event
0 6 12 18 240
0.1
0.2
0.3
0.4
0.5AVR
TAVR
All-Cause Mortality (As Treated)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)All-Cause Mortality at 1 Year
7.0-2.0 -1.0 0.0 6.03.0 4.0 5.0-3.0
Zone of non-inferiority pre-specified margin = 7.5%
1.0 2.0
Non-inferior
Upper one-sided 95% CI
Primary Non-Inferiority Endpoint Met
8.0 %
Difference -1.6%
Upper 1-sided 95% CI4.0%
Non-inferiority
P value= 0.004
AVR (N = 313)
25.2%
TAVR (N = 344)
23.6%
0 6 12 18 240
0.1
0.2
0.3
0.4
0.5AVR
TAVR
All-Cause Mortality (As Treated)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):TF All-Cause Mortality at 1 Year
7.0-4.0 -1.0 0.0 6.03.0 4.0 5.0-5.0
Zone of non-inferiority pre-specified margin = 7.5%
1.0 2.0
Non-inferior
Upper one-sided 95% CI
Secondary TF Non-Inferiority Endpoint Met
8.0 %
Difference -3.9%
Upper 1-sided 95% CI2.6%
Non-inferiority
P value= 0.002
-2.0-3.0
AVR (N = 221)
25.2%
TAVR (N =240 )
21.3%
0 6 12 18 240
0.1
0.2
0.3
0.4
0.5AVR
TAVR
All-Cause Mortality (As Treated)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 Stratified by ITT Trial Arm and Patient Gender
0 6 12 18 240
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1
TAVR Female
AVR Female
Months
All-Cause Mortality Stratified by ITT Trial Arm and Prior CABG
0 6 12 18 240
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1
AVR: CABG No
AVR: CABG Yes
Months
All-Cause Mortality Stratified by ITT Trial Arm and Prior CABG
0 6 12 18 240
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1
TAVR: CABG No
AVR: CABG No
Months
All-Cause Mortality Stratified by ITT trial arm and Moderate/Severe MR
0 6 12 18 240
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1
TAVR MR No TAVR MR Yes AVR MR No AVR MR Yes
Months
P = 0.027 (log rank)
Echo FindingsValvular Regurgitation
30 Days 1 Year
Finding – no. (%) TAVR AVR TAVR AVR
Transvalv. Regurg.Mod/Severe 3 (1.0) 2 (0.9) <.0001 2 (0.9) 0 (0.0) <.0001
Paravalv. Regurg.Mod/Severe 35 (12.2) 2 (0.9) <.0001 15 (6.8) 3 (1.9) <.0001
All Regurg.Mod/Severe
21 (7.7) 4 (1.7) <0.001 12 (5.5) 3 (1.9) <0.001
p-value p-value
Echo FindingsParavalvular Regurgitation
30 Days 1 Year
Finding – no. (%) TAVR AVR TAVR AVR
None 65 (22.6) 168 (73.7) <.0001 73 (32.9) 123 (77.8) <.0001
Trace/Mild 187 (65.2) 58 (25.4) <.0001 134 (60.4) 32 (20.3) <.0001
Mod/Severe 35 (12.2) 2 (0.9) <.0001 15 (6.8) 3 (1.9) <.0001
p-value p-value
Baseline 30 Day 6 Month 1 Year 0.00
0.25
0.50
0.75
1.00
1.25
1.50
1.75
2.00
AVRTAVR
Valv
e A
rea,
cm
2
Aortic Valve AreaAs Treated Trial Arms
TAVRn = 319
AVRn = 297
TAVRn = 279
AVRn = 228
TAVRn = 235
AVRn = 165
TAVRn = 219
AVRn = 155
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