ACC 2015 | San Diego | March 15, 2015 ACC 2015 | San Diego | March 15, 2015 Susheel Kodali, MD Susheel Kodali, MD on behalf of The PARTNER Trial Investigators on behalf of The PARTNER Trial Investigators Clinical and Echocardiographic Clinical and Echocardiographic Outcomes at 30 Days with the Outcomes at 30 Days with the SAPIEN 3 TAVR System in SAPIEN 3 TAVR System in Inoperable, High-Risk and Inoperable, High-Risk and Intermediate-Risk AS Patients Intermediate-Risk AS Patients
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ACC 2015 | San Diego | March 15, 2015 Susheel Kodali, MD on behalf of The PARTNER Trial Investigators Clinical and Echocardiographic Outcomes at 30 Days.
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ACC 2015 | San Diego | March 15, 2015ACC 2015 | San Diego | March 15, 2015
Susheel Kodali, MDSusheel Kodali, MDon behalf of The PARTNER Trial Investigatorson behalf of The PARTNER Trial Investigators
Clinical and Echocardiographic Clinical and Echocardiographic Outcomes at 30 Days with the SAPIEN 3 Outcomes at 30 Days with the SAPIEN 3 TAVR System in Inoperable, High-Risk TAVR System in Inoperable, High-Risk and Intermediate-Risk AS Patientsand Intermediate-Risk AS Patients
Susheel Kodali, MDSusheel Kodali, MD
Within the past 12 months, I or my spouse/partner have had a financial Within the past 12 months, I or my spouse/partner have had a financial interest/arrangement or affiliation with the organization(s) listed below.interest/arrangement or affiliation with the organization(s) listed below.
• Grant/Research SupportGrant/Research Support
• Steering CommitteeSteering Committee
• SAB (Equity)SAB (Equity)
• HonorariaHonoraria
• Edwards Lifesciences, Medtronic, Edwards Lifesciences, Medtronic, Boston Scientific, Claret MedicalBoston Scientific, Claret Medical
Disclosure Statement of Financial InterestDisclosure Statement of Financial Interest
BackgroundBackground
• Based on randomized trials with first generation devices, Based on randomized trials with first generation devices, transcatheter aortic valve replacement (TAVR) has been transcatheter aortic valve replacement (TAVR) has been incorporated into the treatment strategy for high-risk and incorporated into the treatment strategy for high-risk and inoperable patients with severe AS.inoperable patients with severe AS.
• Procedural complications remain a concern with TAVR, Procedural complications remain a concern with TAVR, including stroke, vascular complications, paravalvular leak including stroke, vascular complications, paravalvular leak (PVL) and conduction disturbances.(PVL) and conduction disturbances.
• Addressing these limitations will support TAVR use in Addressing these limitations will support TAVR use in lower risk populations.lower risk populations.
Evolution of the Edwards Balloon-Evolution of the Edwards Balloon-Expandable Transcatheter ValvesExpandable Transcatheter Valves
* Sheath compatibility for a 23 mm valve
2002
Cribier-Edwards
2006
SAPIEN
2009
SAPIEN XT
2013
SAPIEN 3
SAPIEN 3 Transcatheter Heart ValveSAPIEN 3 Transcatheter Heart ValveDistinguishing Features Distinguishing Features
The PARTNER II S3 TrialThe PARTNER II S3 TrialPurposePurpose
To evaluate the safety and efficacy of the SAPIEN 3 To evaluate the safety and efficacy of the SAPIEN 3 transcatheter heart valve system at 30 days in transcatheter heart valve system at 30 days in inoperable, high-risk, and intermediate-risk patients.inoperable, high-risk, and intermediate-risk patients.
Intermediate Risk Operable
(PII S3i)
Intermediate Risk Operable
(PII S3i)
High Risk Operable / Inoperable
(PII S3HR)
High Risk Operable / Inoperable
(PII S3HR)
Symptomatic Severe Aortic Stenosis
ASSESSMENT by Heart Valve Team
n = 1076 Patients
n = 583Patients
ASSESSMENT: Optimal Valve
Delivery Access
ASSESSMENT: Optimal Valve
Delivery Access
SAPIEN 32 Single Arm Non-RandomizedHistorical-Controlled Studies
Transfemoral (TF)
TF TAVRSAPIEN 3
TAA TAVRSAPIEN 3
Transapical /Transaortic (TA/TAo)
TF TAVRSAPIEN 3
PI A SAPIEN
PII A SAVR
Transfemoral (TF)
TAA TAVRSAPIEN 3
Transapical /Transaortic (TA/TAo)
The PARTNER II S3 TrialThe PARTNER II S3 TrialStudy DesignStudy Design
Key Inclusion CriteriaKey Inclusion Criteria
• Risk determined by STS score and heart team:Risk determined by STS score and heart team:– High Risk / Inoperable (S3HR): High Risk / Inoperable (S3HR): STS score > 8 or heart team STS score > 8 or heart team
determinationdetermination
– Intermediate Risk (S3i): Intermediate Risk (S3i): STS score between 4 and 8 or heart STS score between 4 and 8 or heart team determinationteam determination
• Severe aortic stenosis determined by echocardiography:Severe aortic stenosis determined by echocardiography:– Valve area < 0.8 cmValve area < 0.8 cm22 or Valve area index < 0.5 cm or Valve area index < 0.5 cm22/m/m22 and and mean mean
gradient > 40mmHg or peak velocity > 4 m/sgradient > 40mmHg or peak velocity > 4 m/s
Key Exclusion CriteriaKey Exclusion Criteria
Study MethodologyStudy Methodology
• All patients presented on a screening call for approval prior to All patients presented on a screening call for approval prior to implant.implant.
• 3D imaging of annulus (CT or 3D TEE) recommended for S3HR and 3D imaging of annulus (CT or 3D TEE) recommended for S3HR and required for majority of S3i with core lab analysis prior to implant.required for majority of S3i with core lab analysis prior to implant.
• All patients evaluated by a neurologist at baseline and at follow-up All patients evaluated by a neurologist at baseline and at follow-up time points.time points.
• Primary Analysis: Primary Analysis: As treated patientsAs treated patients
• S3HR and S3i combined for echocardiographic analyses (valve S3HR and S3i combined for echocardiographic analyses (valve implant patients).implant patients).
The PARTNER II S3 Trial: The PARTNER II S3 Trial: S3HRS3HRParticipating SitesParticipating Sites
583 Patients Enrolled at 583 Patients Enrolled at 29 US Participating Sites29 US Participating Sites
The PARTNER II S3 Trial: The PARTNER II S3 Trial: S3iS3iParticipating SitesParticipating Sites
1076 Patients Enrolled at 1076 Patients Enrolled at 51 US Participating Sites51 US Participating Sites
The PARTNER II S3 Trial: The PARTNER II S3 Trial: S3HR & S3iS3HR & S3iTop 10 Enrollment SitesTop 10 Enrollment Sites
S3HRS3HR S3iS3iCedars-Sinai Medical Ctr.Cedars-Sinai Medical Ctr.Los Angeles, CALos Angeles, CA
7373 Cedars-Sinai Medical Ctr.Cedars-Sinai Medical Ctr.Los Angeles, CALos Angeles, CA
106106
Columbia University Medical Ctr.Columbia University Medical Ctr.New York, NYNew York, NY
6565 University of PennsylvaniaUniversity of PennsylvaniaPhiladelphia, PAPhiladelphia, PA
6666
Emory UniversityEmory UniversityAtlanta, GAAtlanta, GA
6363 Emory UniversityEmory UniversityAtlanta, GAAtlanta, GA
6262
University of PennsylvaniaUniversity of PennsylvaniaPhiladelphia, PAPhiladelphia, PA
4343 University of Texas, HoustonUniversity of Texas, HoustonHouston, TXHouston, TX
Neil J. WeissmanNeil J. WeissmanMedstar Health Res. Inst., Wash DCMedstar Health Res. Inst., Wash DC
ECG Core LaboratoryECG Core Laboratory
Jose M. DizonJose M. DizonColumbia University/CRF, NYCColumbia University/CRF, NYC
CT Core LaboratoryCT Core Laboratory
Jonathan LeipsicJonathan LeipsicSt. Paul’s Hospital, Vancouver, BCSt. Paul’s Hospital, Vancouver, BC
Study AdministrationStudy Administration
Study Flow: Study Flow: S3HR & S3iS3HR & S3i30 Day Patient Status30 Day Patient Status
0 Withdrawal
3 LTFU
13 Deaths
0 Withdrawal
5 LTFU
12 Deaths
S3HRS3HR S3iS3i
n = 583n = 583n = 583n = 583
n = 570n = 570SAPIEN 3SAPIEN 3n = 570n = 570
SAPIEN 3SAPIEN 3
567 / 570 or 99.5% follow-up567 / 570 or 99.5% follow-upvisits performed at 30 Days visits performed at 30 Days 567 / 570 or 99.5% follow-up567 / 570 or 99.5% follow-upvisits performed at 30 Days visits performed at 30 Days
n = 1076n = 1076n = 1076n = 1076
n = 1064n = 1064SAPIEN 3SAPIEN 3n = 1064n = 1064
SAPIEN 3SAPIEN 3
1059 / 1064 or 99.5% follow-up1059 / 1064 or 99.5% follow-upvisits performed at 30 Days visits performed at 30 Days
1059 / 1064 or 99.5% follow-up1059 / 1064 or 99.5% follow-upvisits performed at 30 Days visits performed at 30 Days
Moderate/Severe PVL at 30 DaysModerate/Severe PVL at 30 DaysEdwards SAPIEN Valves Edwards SAPIEN Valves
PARTNER I and II Trials
SAPIEN SAPIEN XT SAPIEN 3
Conclusions (1)Conclusions (1)
• In high-risk and inoperable patients (S3HR), the SAPIEN 3 In high-risk and inoperable patients (S3HR), the SAPIEN 3 TAVR system demonstrated low mortality and stroke and TAVR system demonstrated low mortality and stroke and excellent clinical outcomes at 30 days:excellent clinical outcomes at 30 days:– Mortality: Mortality: 2.2% (TF 1.6%, TA/TAo 5.4%)2.2% (TF 1.6%, TA/TAo 5.4%)
– Disabling Stroke: Disabling Stroke: 0.9%0.9%
• In intermediate-risk patients (S3i), SAPIEN 3 was In intermediate-risk patients (S3i), SAPIEN 3 was associated with strikingly low mortality and strokes at 30 associated with strikingly low mortality and strokes at 30 days:days:– Mortality:Mortality: 1.1% (TF 1.1%, TA/TAo 1.6%) 1.1% (TF 1.1%, TA/TAo 1.6%)
– Disabling Stroke: Disabling Stroke: 1.0%1.0%
Conclusions (2)Conclusions (2)
• Other important clinical findings with SAPIEN 3 Other important clinical findings with SAPIEN 3 (both S3HR & S3i) include:(both S3HR & S3i) include:– Major vascular complications: Major vascular complications: ~5%~5%
• Significant paravalvular regurgitation with SAPIEN 3 (both Significant paravalvular regurgitation with SAPIEN 3 (both S3HR & S3i) was rare:S3HR & S3i) was rare:– Severe: Severe: 0.1%0.1%
– Moderate: Moderate: 3.7%3.7%
ImplicationsImplications
• The rapid evolution of balloon-expandable TAVR, The rapid evolution of balloon-expandable TAVR, both procedural developments and technical both procedural developments and technical enhancements, represented in the SAPIEN 3 clinical enhancements, represented in the SAPIEN 3 clinical and echo results, indicates at least parity with the and echo results, indicates at least parity with the best surgical outcomes in comparable patients.best surgical outcomes in comparable patients.
• SAPIEN 3 TAVR should now be considered as an SAPIEN 3 TAVR should now be considered as an alternative to surgery, even in lower risk patients with alternative to surgery, even in lower risk patients with aortic stenosis. aortic stenosis.
Dedicated to the Memory of Mike Davidson,Dedicated to the Memory of Mike Davidson,a Cherished Member of Our PARTNER Teama Cherished Member of Our PARTNER Team
Backup SlidesBackup Slides
Primary Endpoint: Primary Endpoint: S3HR S3HR
• Primary Endpoint: Primary Endpoint: Non-Hierarchical composite of Death + Non-Hierarchical composite of Death + All Stroke + Total AR ≥ ModerateAll Stroke + Total AR ≥ Moderate
• Patients in S3HR cohort are confirmed to be comparable Patients in S3HR cohort are confirmed to be comparable to patients in P1A SAPIEN group via propensity modeling to patients in P1A SAPIEN group via propensity modeling on baseline characteristics.on baseline characteristics.
• Overall treatment effect is adjusted for propensity quintiles Overall treatment effect is adjusted for propensity quintiles defined by propensity scores.defined by propensity scores.
• Patients that received SAPIEN 3 have 9% lower event rate Patients that received SAPIEN 3 have 9% lower event rate than patients that received SAPIEN.than patients that received SAPIEN.
Zone of non-inferiorityZone of non-inferioritypre-specified pre-specified margin = 7.5%margin = 7.5%-4.5-4.5-13.9-13.9
-14.0-14.0
*Weighted*WeightedPrimary Endpoint: Primary Endpoint: Non-Hierarchical Composite ofNon-Hierarchical Composite ofDeath + All Stroke + Total AR ≥ ModerateDeath + All Stroke + Total AR ≥ Moderate