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Transcatheter Aortic Valve Implantation in Inoperable Patients with Severe Aortic Stenosis. Press Conference. Martin B. Leon, MD on behalf of the PARTNER Investigators. TCT 2010; Washington, DC; September 23, 2010. PARTNER Study Design. Total = 1058 patients. n=358. n= 700. - PowerPoint PPT Presentation
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Martin B. Leon, MDMartin B. Leon, MDon behalf of theon behalf of the
PARTNER InvestigatorsPARTNER InvestigatorsTCT 2010; Washington, DC; September 23, 2010TCT 2010; Washington, DC; September 23, 2010
Transcatheter Aortic Valve Transcatheter Aortic Valve Implantation in Inoperable Patients Implantation in Inoperable Patients
with Severe Aortic Stenosiswith Severe Aortic Stenosis
Press ConferencePress Conference
Symptomatic Severe Aortic StenosisSymptomatic Severe Aortic Stenosis
ASSESSMENT: High Risk AVR Candidate3105 Total Patients Screened
PARTNER Study DesignPARTNER Study Design
High Risk TAHigh Risk TA
ASSESSMENT: Transfemoral
Access
TAVITAVITransTrans
femoralSurgical Surgical
AVRAVR
High Risk TFHigh Risk TF
Primary Endpoint: All Cause Mortality (1 yr)Primary Endpoint: All Cause Mortality (1 yr)(Non-inferiority)(Non-inferiority)
TAVITAVITransTrans
femoralfemoralSurgical Surgical
AVRAVR
1:1 Randomization1:1 Randomization
VS
VS
Standard Standard TherapyTherapy
(usually BAV)(usually BAV)
ASSESSMENT: Transfemoral
Access
Not In Study
TAVITAVITransTrans
femoralfemoral
Primary Endpoint: All Cause Mortality over Primary Endpoint: All Cause Mortality over length of trial (Superiority)length of trial (Superiority)
1:1 Randomization
VS
Total = 1058 patients2 Parallel Trials:
Individually PoweredHigh RiskHigh Riskn= 700 InoperableInoperable n=358
Primary and Co-Primary EndpointsPrimary and Co-Primary Endpoints
• PRIMARY: All-cause mortality over the duration PRIMARY: All-cause mortality over the duration of the studyof the study Superiority test (two-sided), 85% power to detect a Superiority test (two-sided), 85% power to detect a
difference, difference, αα = 0.05, sample size = 350 total patients = 0.05, sample size = 350 total patients
• CO-PRIMARY: Hierarchical composite of CO-PRIMARY: Hierarchical composite of all-cause mortality and repeat hospitalizationall-cause mortality and repeat hospitalization Non-parametric method described by Finkelstein and Non-parametric method described by Finkelstein and
Schoenfeld (multiple pair-wise comparisons)Schoenfeld (multiple pair-wise comparisons) > 95% power to detect a difference, > 95% power to detect a difference, αα = 0.05 = 0.05
• Positive study if both endpoints P < 0.05, or if Positive study if both endpoints P < 0.05, or if either endpoint is < 0.025either endpoint is < 0.025
Study DevicesStudy Devices
Retroflex 1Edwards-SAPIEN THVEdwards-SAPIEN THV
23mm and 26mm23mm and 26mmvalve sizesvalve sizes
22F and 24F22F and 24Fsheath sizessheath sizes
Inclusion CriteriaInclusion Criteria
• Severe calcific aortic stenosis defined as echo derived valve area of < 0.8 cm2 (EOA index <0.5cm2), and mean gradient > 40 mmHg or jet velocity > 4.0 m/s
• NYHA functional class II or greater• Risk of death or serious irreversible Risk of death or serious irreversible
morbidity as assessed by cardiologist morbidity as assessed by cardiologist and two surgeons must exceed 50% and two surgeons must exceed 50%
All Cause All Cause MortalityMortality
Numbers at RiskNumbers at Risk TAVITAVI 179179 138138 122122 6767 2626 Standard RxStandard Rx 179179 121121 8383 4141 1212
All-
caus
e m
orta
lity
(%)
Months
HR [95% CI] =0.54 [0.38, 0.78]
P (log rank) < 0.0001
Standard Rx TAVI
All Cause All Cause MortalityMortality
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%
• Compare, at random, every TAVI patient with every Compare, at random, every TAVI patient with every Standard Rx patient; Standard Rx patient; 179 x 179 (32,041) patient pairs, 179 x 179 (32,041) patient pairs, which did better?which did better?
• #1, compare “time to death”#1, compare “time to death” 72% chance that we know who died first72% chance that we know who died first If so, 63% chance that Standard Rx patient died first and If so, 63% chance that Standard Rx patient died first and
37% chance that TAVI patient died first37% chance that TAVI patient died first• #2, if necessary, compare “time to repeat #2, if necessary, compare “time to repeat
hospitalization” hospitalization” 17% chance that we know who had repeat hosp first17% chance that we know who had repeat hosp first If so, 75% chance that Standard Rx patient had repeat If so, 75% chance that Standard Rx patient had repeat
hosp first and 25% chance that TAVI patient had repeat hosp first and 25% chance that TAVI patient had repeat hosp first hosp first
Finklestein & Schoenfeld AnalysisFinklestein & Schoenfeld Analysis(hierarchical multiple pair-wise comparison)(hierarchical multiple pair-wise comparison)
FS MethodFS MethodProduces a Produces a
P-valueP-value< 0.0001< 0.0001
OutcomeOutcome 30 Days 30 Days n=179n=179
TAVI Standard Rx P-value
1 Year 1 Year n=179n=179
TAVI Standard Rx P-value
Clinical Outcomes at 30 Days & 1 YearClinical Outcomes at 30 Days & 1 Year
Myocardial infarction All (%) 0 0 . 0.6 0.6 1.00 Peri-procedural (% 0 0 . 0 0 .
Stroke or TIA
All (%) 6.7 1.7 0.03 10.6 4.5 0.04 TIA (%) 0 0 . 0.6 0 1.00 Minor stroke (%) 1.7 0.6 0.62 2.2 0.6 0.37 Major stroke (%) 5.0 1.1 0.06 7.8 3.9 0.18
Death (all) or major stroke (%) 8.4 3.9 0.12 33.0 50.3 0.001
Repeat hospitalization (%) 5.6 10.1 0.17 22.3 44.1 <.0001
Death (all) or repeat hosp (%) 10.6 12.3 0.74 42.5 70.4 <.0001
Death All (%) 5.0 2.8 0.41 30.7 49.7 0.0004 Cardiovascular (%) 4.5 1.7 0.22 19.6 41.9 <.0001
OutcomeOutcome 30 Days 30 Days n=179n=179
TAVI Standard Rx P-value
1 Year 1 Year n=179n=179
TAVI Standard Rx P-value
Clinical Outcomes at 30 Days & 1 YearClinical Outcomes at 30 Days & 1 Year
Acute kidney injury Creatinine >3 mg/dL (%) 0 1 1.00 1.1 2.8 0.45 RRT (%) 1.1 1.7 1.00 1.7 3.4 0.50
Cardiac re-intervention BAV (%) 0.6 1.1 1.0 0.6 36.9 <.0001
Re-TAVI (%) 1.7 na 1.7 na
AVR (%) 0 1.7 0.25 1.1 9.5 <.0001Endocarditis (%) 0 0 . 1.1 0.6 0.31
Vascular complications All (%) 30.7 5.0 <.0001 32.4 7.3 <.0001
Major (%) 16.2 1.1 <.0001 16.8 2.2 <.0001
Bleeding - major (%) 16.8 3.9 <.0001 22.3 11.2 0.007
Arrhythmias New atrial fibrillation (%) 0.6 1.1 1.00 0.6 1.7 0.62
New pacemaker (%) 3.4 5.0 0.60 4.5 7.8 0.27
Walking Distance
P = 0.002
Wal
king
dis
tanc
e (m
eter
s)
Baseline 30 Days
Six-Minute Walk TestsSix-Minute Walk Tests
P = 0.004
1 Year
P = 0.67
P = 0.55
NYHA Class Over TimeNYHA Class Over TimeSurvivorsSurvivors
P = 0.68 P < 0.0001 P < 0.0001 P < 0.0001
I II III IV
TAVI Standard Rx TAVI Standard Rx TAVI Standard Rx TAVI Standard Rx
Perc
ent
TreatmentTreatmentVisitVisit
Baseline 30 Day 6 Month 1 Year
BaselineN=163
30 DayN=143
6 MonthsN=100
1 YearN=89
Mea
n G
radi
ent (
mm
Hg)
50
40
30
20
60
70
10
0
Error bars = ± 1 Std DevError bars = ± 1 Std Dev
Mean Gradients Over TimeMean Gradients Over Time
P < 0.0001P < 0.0001
33.033.039.539.5
44.444.4
43.243.2 12.111.310.8
44.6
Standard Rx TAVI
Paravalvular Regurgitation: TAVIParavalvular Regurgitation: TAVI
No changes over time
None/Trace
MildModerate
Severe
30 Day 6 Month 1 Year
Conclusions - 1Conclusions - 1
In patients with severe AS and symptoms, In patients with severe AS and symptoms, who are not suitable candidates for surgery…who are not suitable candidates for surgery…
• Standard therapy (including BAV in 83.8% of pts) did not alter the dismal natural history of AS; all-cause and cardiovascular mortality at 1 year was 50.7% and 44.6% respectively
• Transfemoral balloon-expandable TAVI, despite limited operator experience and an early version of the system, was associated with acceptable 30-day survival (5% after randomization in the intention-to-treat population)
Conclusions - 2Conclusions - 2
• TAVI was superior to standard therapy, markedly reducing the rate of… all-cause mortality by 46%, P < 0.0001,
NNT = 5.0 pts cardiovascular mortality by 61%, P < 0.0001,
NNT = 4.1 pts all-cause mortality and repeat hospitalization
hierarchical (FS method), P < 0.0001 non-hierarchical (KM analysis) by 54%,
P < 0.0001, NNT = 3.4 pts
Conclusions - 3Conclusions - 3
• TAVI improved cardiac symptoms (NYHA class, P < 0.0001) and six minute walking distance (P = 0.002), after 1-year follow-up
• TAVI resulted in more frequent complications at 30 days, including… major vascular complications, 16.2% vs.
1.1%, P < 0.0001 major bleeding episodes, 16.8% vs. 3.9%,
P < 0.0001 major strokes, 5.0% vs. 1.1%, P = 0.06
Conclusions - 4Conclusions - 4
• Serial echocardiograms in TAVI patients indicated… reduced mean gradients (P < 0.0001) which
were unchanged during 1-year FU frequent paravalvular AR, which was usually
trace or mild (~90%), remained stable during 1-year FU, and rarely required further Rx.
Clinical Implications Clinical Implications
• Balloon-expandable TAVI should be the new standard of care for patients with aortic stenosis who are not suitable candidates for surgery!
• Next generation devices (e.g. SAPIEN XT) may help to reduce the frequency of procedure-related complications in the future.
• The ultimate value of TAVI will depend on careful assessment of bioprosthetic valve durability, which will mandate obligatory long-term clinical and echocardiography FU of all TAVI patients.
September 22, 2010 on NEJM.orgSeptember 22, 2010 on NEJM.org
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