lessons from tavr randomized trials and registries e murat tuzcu, md professor of medicine cleveland...
Post on 15-Jan-2016
217 views
TRANSCRIPT
Lessons from TAVR Randomized Trials and Registries
E Murat Tuzcu, MDProfessor of Medicine
Cleveland Clinic
Financial disclosures: NonePARTNER Executive Committee member
Edwards Transcatheter Valve Evolution
UntreatedEquine Tissue
Edwards SAPIEN™ August, 2007
TreatedBovine Tissue
AndersenPig implant, May ’89
Cribier-Edwards™FIM, April 2002
Sapien XT™ January, 2010
TFX TreatedBovine /CC
UntreatedEquine Tissue
CoreValve Revalving
Generation 1Generation 125 Fr25 Fr
Generation 2Generation 221 Fr21 Fr
Generation 3Generation 318 Fr18 Fr
Dec 2006Dec 2006No Support No Support
No AnesthesiaNo Anesthesia
2005-2006 (June)2005-2006 (June)CP By-Pass + TandemHeartCP By-Pass + TandemHeart
Percutaneous SupportPercutaneous Support
2004-20052004-2005Surgical Fem-FemSurgical Fem-Fem
CP By-PassCP By-Pass
30-day Mortality 30-day Mortality
Study (%)Study (%)
REVIVE/REVIVALREVIVE/REVIVALaa
VANCOUVERVANCOUVERbb
PARTNER EUPARTNER EUcc
SOURCESOURCEdd
CANADIANCANADIANee
FRENCH RegFRENCH Regff
UK RegUK Reggg
nn
161161
114114
5959
463463
345345
9595
172172
AgeAge
83.783.7
83.983.9
82.382.3
81.781.7
8181
83.283.2
8383
Mortality (%)Mortality (%)
11.211.2
7.97.9
8.18.1
6.36.3
10.410.4
8.48.4
8.98.9
ES/STSES/STS
34.3/13.134.3/13.1
30.3/-30.3/-
25.7/11.325.7/11.3
25.7/-25.7/-
-/9.8-/9.8
25.6/15.425.6/15.4
2020
Transfemoral TAVI
a. Kodali et al TCT 2008a. Kodali et al TCT 2008b. Webb TCT 2008b. Webb TCT 2008c. Schachinger et al Euro PCR 2009c. Schachinger et al Euro PCR 2009
d. Thomas et al Euro PCR 2009d. Thomas et al Euro PCR 2009e. Rodes-Cabau et al. JACC 2010;55:In Presse. Rodes-Cabau et al. JACC 2010;55:In Pressf. Eltchaninoff H. AHA 2009f. Eltchaninoff H. AHA 2009g. LudmanEuroPCR 2010g. LudmanEuroPCR 2010
1.01.0
0.00.0
0.20.2
0.40.4
0.60.6
0.80.8
REVIVALVANCOUVER
CANADIAN UK Registry
00 22 44 66 88 1010 1212
MonthMonth
SOURCE
1.01.0
75.8%73.8%81.1%75.0%79.5%
One Year SurvivalOne Year Survival
Transfemoral TAVI
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
ASSESSMENT: High-Risk AVR Candidate3,105 Total Patients Screened
Total = 1,057 patients
2 Parallel Trials: Individually Powered
StandardTherapyStandardTherapy
ASSESSMENT: Transfemoral
Access
ASSESSMENT: Transfemoral
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)
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
All Cause Mortality
Numbers at RiskNumbers at Risk
TAVITAVI 179179 138138 122122 6767 2626 Standard RxStandard Rx 179179 121121 8383 4141 1212
∆ at 1 yr = 20.0%NNT = 5.0 pts
Standard Rx
TAVI
All-
caus
e m
orta
lity
(%)
Months
0
20
40
60
80
100
50.7%
30.7% HR [95% CI] =0.54 [0.38, 0.78]
P (log rank) < 0.0001
TAVI Standard Rx TAVI Standard Rx TAVI Standard Rx TAVI Standard Rx
DeadI II III IV
Per
cent
NYHA Class Over TimeNYHA Class Over TimeAll patientsAll patients
TreatmentTreatmentVisitVisit
P = 0.68 P < 0.0001 P < 0.0001 P < 0.0001
Aortic Valve Mean Gradient (Core Lab) (mmHg)
*
**
*
Douglas et al ACC 2011
Clinical Outcomes at 30 Days and 1 Year
Major VascularComplications
P<0.0001 P<0.0001
TAVI (n=179) Standard Rx (n=179)
per
cent
Major Stroke
P = 0.06 P = 0.18
Published Cost Effectiveness Estimates
Clinical Implications
• Balloon-expandable TAVI should be the new standard of care for patients with aortic stenosis who are not suitable candidates for surgery!
N = 179
N = 358InoperableInoperable
StandardTherapyStandardTherapy
ASSESSMENT: Transfemoral
Access
ASSESSMENT: Transfemoral
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)
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
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 AVRAVRVSVS
N = 248 N = 104 N = 103N = 244
PARTNER Study DesignPARTNER Study Design
Symptomatic Severe Aortic StenosisSymptomatic 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: Transfemoral
Access
ASSESSMENT: Transfemoral
Access
Transapical (TA)Transapical (TA)Transfemoral (TF)Transfemoral (TF)
1:1 Randomization1:1 Randomization1:1 Randomization1:1 Randomization
YesYes NoNo
Characteristic TAVR (N = 348) AVR (N = 351) p-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
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 6.00.79
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
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:All-Cause Mortality at 1 Year
HR [95% CI] =0.93 [0.71, 1.22]
P (log rank) = 0.62
30 Days 1 Year
OutcomeTAVR
(N = 348)AVR
(N = 351)p-value
TAVR(N = 348)
AVR(N = 351)
p-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 All Patients (N=699)
30 Days 1 Year
OutcomeTAVR
(N = 348)AVR
(N = 351)TAVR
(N = 348)AVR
(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 All Patients (N=699)
p-value p-value
0 - No symptoms. 1 - No significant disability. Able to carry out all usual activities, despite
some symptoms.
2 - Slight disability. Able to look after own affairs without assistance, but unable to carry out all previous activities.
3 - Moderate disability. Requires some help, but able to walk unassisted. 4 - Moderately severe disability. Unable to attend to own bodily needs
without assistance, and unable to walk unassisted. 5 - Severe disability. Requires constant nursing care and attention,
bedridden, incontinent. 6 - Dead.
The Modified Rankin Scale
Minor
Major
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) 0.046 9 (8.7) 7 (7.6) 0.79
Mortality and Major Stroke at 30 Days
Major Stroke 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 13 (3.8) 7 (2.1) 0.20 7 (2.9) 4 (1.7) 0.37 6 (5.8) 3 (3.2) 0.37
AT 13 (3.8) 7 (2.3) 0.25 6(2.5) 3 (1.4) 0.37 7 (7.0) 4 (4.4) 0.45
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
Major Stroke 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 17 (5.1) 8 (2.4) 0.07 9 (3.8) 4(1.7) 0.15 8 (8.3) 4 (4.3) 0.26
AT 17 (5.2) 8 (2.7) 0.11 8 (3.5) 3(1.4) 0.15 9 (9.4) 5(5.9) 0.37
Mortality and Major Stroke at 1 year
5
4
3
9
0
2
4
6
8
10
0-5 Days 6-30 Days 31Days - 1 Year >1Year
TAVR Neuro Events in PARTNER BN
um
be
r of
Eve
nts
Nu
mb
er
of E
ven
ts
00
22
44
66
88
1010
5strokes0-3 day
8 strokes occurred when patients were in AF
Paravalvular Aortic Regurgitation
P< 0.001 P< 0.001 P< 0.001
1 Year6 Months30 Days
Pat
ient
s, %
None Trace Mild Moderate Severe
ImplicationsImplications
•TAVR is an acceptable alternative to AVR in selected high-risk operable patients.
• A multidisciplinary valve team benefits patients and recommended for all valve centers.
• Future RCT should focus on lower risk patients who are candidates for operation.