A Randomized Evaluation of the SAPIEN XT
`Transcatheter Valve System in Patients with
`Aortic Stenosis Who Are Not Candidates for
`Surgery: PARTNER II, Inoperable Cohort
`
`
`
`Martin B. Leon, MD
`on behalf of The PARTNER Trial Investigators
`
`ACC 2013 | San Francisco | March 10, 2013
`
`Page 01 of 42
`
`
`Transcatheter Valve System in Patients with
`Aortic Stenosis Who Are Not Candidates for
`Surgery: PARTNER II, Inoperable Cohort
`
`
`
`Martin B. Leon, MD
`on behalf of The PARTNER Trial Investigators
`
`ACC 2013 | San Francisco | March 10, 2013
`
`Page 01 of 42
`
`
`
`Disclosure Statement of Financial Interest
`
`Martin B. Leon, MD
`
`Within the past 12 months, I or my spouse/partner have had a financial
`interest/arrangement or affiliation with the organization(s) listed below.
`
`Affiliation/Financial Relationship
`
`Company
`
`• Grant/Research Support
`
`
`• Consulting Fees/Honoraria
`
`• Major Stock Shareholder/Equity
`
`
`• Abbott, Boston Scientific, Edwards
`Lifesciences, Medtronic
`
`
`• None
`
`
`• Sadra, Claret, Valve Medical, Apica
`
`Page 02 of 42
`
`
`
`Background (1)
`
`• In the PARTNER I randomized trials, patients with
`symptomatic severe aortic stenosis, treated using the
`balloon-expandable SAPIEN transcatheter heart valve
`system, had reduced mortality compared with standard
`therapy in patients who could not undergo surgery
`(“inoperable”) and had similar mortality compared to
`surgical AVR in patients who were at high-risk for surgery.
`
`Page 03 of 42
`
`
`
`Background (2)
`
`• However, SAPIEN was associated with peri-procedural
`complications, including strokes, vascular events, and
`paravalvular regurgitation.
`
`• The new lower-profile SAPIEN XT, currently in general
`clinical use around the world, incorporates important
`enhancements to the valve support frame, the valve
`leaflet geometry, and the delivery system which may be
`associated with improved clinical outcomes.
`
`Page 04 of 42
`
`
`
`Purpose of PARTNER II
`Inoperable Cohort
`
`• To compare the safety and effectiveness of the new
`SAPIEN XT versus the FDA-approved SAPIEN in a
`randomized controlled trial for patients with symptomatic
`severe aortic stenosis who cannot have surgery
`(“inoperable”).
`
`
`• To apply rigorous clinical trial methodologies including
`systematic serial neurologic assessments and VARC 2
`definitions* for clinical outcomes.
`
`* Kappetein AP, et al. J Am Coll Cardiol 2012;60:1438-54
`
`Page 05 of 42
`
`
`
`The PARTNER II Inoperable Cohort
`Study Design
`
`Symptomatic Severe Aortic Stenosis
`
`ASSESSMENT by Heart Valve Team
`
`Inoperable
`
`ASSESSMENT: Transfemoral Access
`
`1:1 Randomization
`
`n = 560
`Randomized
`Patients
`
`TF TAVR
`SAPIEN XT
`
` VS
`
`TF TAVR
`SAPIEN
`
`Primary Endpoint: All-Cause Mortality + Disabling
`Stroke + Repeat Hospitalization at One Year
`(Non-inferiority)
`
`Page 06 of 42
`
`
`
`The PARTNER II Trial
`Study Design
`
`Symptomatic Severe Aortic Stenosis
`
`ASSESSMENT by Heart Valve Team
`
`n = 2000
`Randomized
`Patients
`
`Operable
`(STS ≥4)
`
`Two Parallel
`Randomized Trials
`+6 Nested Registries
`
`Inoperable
`
`n = 560
`Randomized
`Patients
`
`Yes
`
`ASSESSMENT:
`Transfemoral
`Access
`
`No
`
`ASSESSMENT:
`Transfemoral
`Access
`
`Transfemoral (TF)
`
`Transapical (TA) /
`TransAortic (TAo)
`
`Yes
`
`1:1 Randomization
`
`1:1 Randomization
`
`1:1 Randomization
`
`6 Nested
`Registries
`
`Sample
`Size
`
`NR1 (Sm Vessel)
`
`100
`
`NR2 (Transapical)
`
`100
`
`TF TAVR
`SAPIEN XT
`
`Surgical
`AVR
`
` VS
`
`TAVR:
`TA / TAo
`SAPIEN XT
`
` VS
`
`Surgical
`AVR
`
`TF TAVR
`SAPIEN XT
`
` VS
`
`TF TAVR
`SAPIEN
`
`NR3 (ViV)
`
`NR4 (TAo)
`
`Primary Endpoint: All-Cause Mortality +
`Disabling Stroke at Two Years
`(Non-inferiority)
`
`Primary Endpoint: All-Cause
`Mortality + Disabling Stroke +
`Repeat Hospitalization at One Year
`(Non-inferiority)
`
`NR5 (29 mm TF)
`
`NR6 (29 mm TA)
`
`100
`
`100
`
`50
`
`50
`
`Page 07 of 42
`
`
`
`Primary Endpoint
`
`• A non-hierarchical composite of all-cause mortality,
`disabling stroke*, and re-hospitalization for symptoms
`of aortic stenosis and/or complications of the valve
`procedure.
`
`
`• Intention-to-treat population, all patients followed for at
`least one year, non-inferiority trial arm comparison.
`
`* Disabling stroke = CEC adjudicated stroke event by a neurologist with a modified
` Rankin score of 2 or greater at 90-day evaluation
`
`Page 08 of 42
`
`
`
`Other Important Endpoints
`VARC 2 Definitions
`
`SAFETY
`• Cardiovascular mortality
`• Major vascular complications
`• All strokes and TIAs
`• Peri-procedural Mis
`• Acute kidney injury
`• Life-threatening or disabling
`bleeding
`• No. of transfusions
`• New permanent pacemakers
`• New onset atrial fibrillation
`• ≥ 2 THV implants
`• Repeat intervention
`• Endocarditis
`
`EFFICACY
`• NYHA class
`• QOL instruments
`• 6-minute walk test
`• Days alive out-of-hospital
`• ICU and index hospital LOS
`
`ECHO VALVE
`PERFORMANCE
`• Mean and peak AV gradient
`• Effective orifice area (and index)
`• LV function (ejection fraction)
`• Paravalvular and total AR
`• Structural valve deterioration
`
`Page 09 of 42
`
`
`
`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
`
`
`
`• “Inoperable”: Risk of death or serious irreversible
`morbidity as assessed by a cardiologist and two surgeons
`must exceed 50%
`
`Page 10 of 42
`
`
`
`Key Exclusion Criteria
`
`Anatomic:
`• Aortic annulus diameter (echo measurement) < 18 mm
`or > 25 mm
`
`• Iliac-femoral anatomy precluding safe sheath insertion
`(vessel size ≥7 mm diameter)
`
`• Severe LV dysfunction (LVEF < 20%)
`
`• Untreated CAD requiring revascularization
`
`Clinical:
`• Serum Cr > 3.0 mg/dL or dialysis dependent
`
`• Acute MI within 1 month
`
`• CVA or TIA within 6 months
`
`• Hemodynamic instability
`
`Page 11 of 42
`
`
`
`Edwards SAPIEN vs SAPIEN XT
`Transcatheter Heart Valves
`
`SAPIEN THV
`
`Stainless Steel
`
`SAPIEN XT THV
`
`Cobalt-chromium
`
`NEW FRAME GEOMETRY
`• Less metal content
`• Lower crimp profile
`
`
`NEW FRAME MATERIAL
`• Cobalt-chromium
`• Greater tensile and yield
`strength
`
`
`
`NEW LEAFLET GEOMETRY
`• Partially closed
`
`RetroFlex 3
`
`NovaFlex
`
`Page 12 of 42
`
`
`
`Sheath Size Comparison
`
`Valve
`
`Valve
`Size
`
`Sheath
`ID
`
`Sheath
`OD
`
`SAPIEN THV
`
`23mm
`
`22F
`
`SAPIEN XT THV 23mm
`
`18F
`
`SAPIEN THV
`
`26mm
`
`24F
`
`SAPIEN XT THV 26mm
`
`19F
`
`25F
`(8.4mm)
`
`22F
`(7.2mm)
`
`28F
`(9.2mm)
`
`23F
`(7.5mm)
`
`Minimum
`Vessel
`Diameter
`
`7.0mm
`
`6.0mm
`
`8.0mm
`
`6.5mm
`
`33% reduction in CSA
`
`Page 13 of 42
`
`
`
`The PARTNER II Inoperable Cohort
`Participating Sites
`
`Univ. of Washington
`Seattle, WA
`
`
`Intermountain
`Medical Center
`Murray, UT
`
`Stanford
`University
`Palo Alto, CA
`
`Cedars-Sinai
`Medical Center
`Los Angeles, CA
`
`Scripps Green Hospital
`La Jolla, CA
`
`MN Heart Institute
`Minneapolis, MN
`
`Mayo Clinic
`Rochester, MN
`
`Rush Univ.
`Chicago, IL
`
`NorthShore Univ.
`Evanston, IL
`
`William Beaumont Hospital
`Royal Oak, MI
`
`
`Northwestern Univ.
`Chicago, IL
`
`Brigham Women’s
`Hospital
`Mass. General Hospital
`Boston, MA
`Boston, MA
`The Christ Hospital
`Cincinnati, OH
`
`
`Columbia University
`New York, NY
`Cornell University
`New York, NY
`
`Univ. of Pennsylvania
`
`Philadelphia, PA
`
`St. Luke’s Hospital
`Kansas City, MO
`
`Cleveland Clinic
`Cleveland, OH
`
`Barnes-Jewish Hospital
`
`Saint Louis, MO
`
`
`
`
`OK Cardiology
`Research Group
`Oklahoma City, OK
`
`
`Medical City
`Dallas
`Dallas, TX
`
`
`Univ. of Virginia
`Charlottesville, VA
`
`Washington Hospital Center
`Washington, DC
`
`Emory University
`Atlanta, GA
`
`Ochsner Foundation
`New Orleans, LA
`
`Univ. of TX, Houston
`Houston, TX
`
`560 Patients Enrolled at
`28 US Participating Sites
`
`Univ. of Miami
`Miami, FL
`
`Page 14 of 42
`
`
`
`PARTNER II Inoperable Cohort
`Enrollment by Site (1 of 2)
`
`Cedars-Sinai Medical Ctr.
`Los Angeles, CA
`Wen Cheng & Raj Makkar
`
`Columbia University
`New York, NY
`Susheel Kodali & Mathew Williams
`
`Emory University
`Atlanta, GA
`Vasilis Babaliaros & Vinod Thourani
`
`University of Pennsylvania
`Philadelphia, PA
`Joseph Bavaria & Howard Herrmann
`
`Washington Hospital Ctr.
`Washington, DC
`Paul Corso & Augusto Pichard
`
`Medical City Dallas
`Dallas, TX
`David Brown & Todd Dewey
`
`Cleveland Clinic
`Cleveland, OH
`Lars Svensson & Murat Tuzcu
`
`OK Cardiology Research
`Oklahoma City, OK
`Mark Bodenhamer & Mohammad Ghani
`
`87
`
`75
`
`58
`
`56
`
`37
`
`33
`
`25
`
`19
`
`Intermountain Medical Ctr.
`Murray, UT
`Kent Jones & Brian Whisenant
`
`Ochsner Hospital
`New Orleans, LA
`Stephen Ramee & Patrick Parrino
`
`Barnes-Jewish Hospital
`Saint Louis, MO
`Hersh Maniar, Jr. & Alan Zajarias
`
`The Christ Hospital
`Cincinnati, OH
`Tom Ivey & Dean Kereiakes
`
`Cornell University
`New York, NY
`Karl Krieger & Chiu Wong
`
`Stanford University
`Palo Alto, CA
`Craig Miller & Alan Yeung
`
`Mayo Clinic
`Rochester, MN
`Kevin Greason & Verghese Mathew
`
`Scripps Green Hospital
`La Jolla, CA
`Scot Brewster & Paul Teirstein
`
`18
`
`17
`
`16
`
`15
`
`13
`
`12
`
`10
`
`9
`
`Page 15 of 42
`
`
`
`PARTNER II Inoperable Cohort
`Enrollment by Site (2 of 2)
`
`William Beaumont Hospital
`Royal Oak, MI
`George Hanzel & Francis Shannon
`
`Northwestern University
`Chicago, IL
`Charles Davidson & Chris Malaisrie
`
`University of Texas, Houston
`Houston, TX
`Anthony Estrera & Richard Smalling
`
`Massachusetts General Hospital
`Boston, MA
`Igor Palacios & Gus Vlahakes
`
`3
`
`2
`
`2
`
`1
`
`University of Miami
`Miami, FL
`Alan Heldman & Donald B. Williams
`
`University of Virginia
`Charlottesville, VA
`Irving Kron & Scott Lim
`
`NorthShore University
`Evanston, IL
`Ted Feldman & Paul Pearson
`
`Rush University
`Chicago, IL
`Zyiad M. Hijazi & Robert March
`
`Minneapolis Heart Institute
`Minneapolis, MN
`Vibhu Kshettry & Wesley Pedersen
`
`St. Luke’s Hospital (MAHI)
`Kansas City, MO
`Michael Borkon & Adnan Chhatriwalla
`
`University of Washington
`Seattle, WA
`Mark Reisman & Edward Verrier
`
`Brigham Women’s Hospital
`Boston, MA
`Ralph Bolman, III & Frederick G. Welt
`
`9
`
`9
`
`8
`
`8
`
`7
`
`4
`
`4
`
`3
`
`Page 16 of 42
`
`
`
`PARTNER II Inoperable Cohort
`Enrollment Cadence
`
`Monthly Enrollment
`
`140
`
`120
`
`100
`
`80
`
`60
`
`40
`
`20
`
`0
`
`Last pt enrolled: February 10, 2012
`Last pt follow-up: March 1, 2013
`
`58
`
`55
`
`60
`
`57
`
`74
`
`41
`
`42
`
`29
`
`120
`
`23
`
`600
`
`500
`
`400
`
`300
`
`200
`
`100
`
`Cumulative Enrollment
`
`1
`
`0
`
`Apr-11 May-11 Jun-11 Jul-11 Aug-11 Sep-11 Oct-11 Nov-11 Dec-11 Jan-12 Feb-12
`
`Page 17 of 42
`
`
`
`Study Administration
`
`Co-Principal Investigators
`
`Echo Core Laboratory
`
`Martin B. Leon, Craig R. Smith
`Columbia University Medical Ctr, NYC
`
`Chairman: Wael A. Jaber
`Cleveland Clinic, C5 Research
`
`Executive Committee
`
`Quality of Life and Cost-Effectiveness
`
`Martin B. Leon, Michael Mack,
`D. Craig Miller, Jeffrey W. Moses,
`Craig R. Smith, Lars G. Svensson,
`E. Murat Tuzcu, John G. Webb
`Neurology: Thomas Brott
`
`Data & Safety Monitoring Board
`
`Chairman: Joseph P. Carrozza
`Caritas, St. Elizabeth Med Ctr, Boston
`
`Members: Blase Carabello, Andrew
`Wechsler, Eric Peterson
`Neurology: K. Michael Welch
`
`Clinical Events Committee
`
`Chairman: Venu Menon
`Cleveland Clinic, C5 Research
`
`
`
`
`
`Chairman: David J. Cohen
`Mid America Heart Institute, Kansas City
`
`Independent Biostatistical
`Core Laboratory
`
`Helen Parise
`Cardiovascular Research Foundation, NYC
`
`Eugene Blackstone
`Cleveland Clinic Foundation, Cleveland, OH
`
`Publications Committee
`
`Co-Located at: Columbia-CRF and Cleveland
`Clinic Foundation
`
`Sponsor
`
`Edwards Lifesciences: Jodi J. Akin
`
`Page 18 of 42
`
`
`
`Study Methodology
`
`• Every case reviewed by web-based conference call
`before enrollment
`
`• All patients followed for at least one year
`
`• Primary analysis performed by intention-to-treat (ITT),
`although as-treated (AT) analyses performed when
`appropriate
`
`• Event rates as Kaplan-Meier estimates
`
`• Composite analyses pre-specified
`
`• 100% data monitoring of clinical events
`
`• All 30-day events CEC adjudicated (>99%)
`
`• 1-year primary endpoint events = CEC adjudicated (89%)
`
`Page 19 of 42
`
`
`
`Baseline Patient Characteristics:
`Demographics (ITT)
`
`SAPIEN
`(n=276)
`
`SAPIEN XT
`(n=284)
`
`Characteristic
`
`n
`
`n
`
`p-value
`
`Age - yrs (mean ± SD)
`
`276
`
`84.6 ± 8.6
`
`284
`
`84.0 ± 8.7
`
`0.44
`
`Male (%)
`
`142
`
`51.4%
`
`141
`
`49.6%
`
`0.67
`
`BMI - kg/m2 (mean ± SD)
`
`275
`
`27.4 ± 6.2
`
`283
`
`28.1 ± 7.3
`
`0.42
`
`STS Score (mean ± SD)
`
`276
`
`11.0 ± 5.7
`
`284
`
`10.3 ± 5.4
`
`0.15
`
`NYHA Class III or IV (%) 265
`
`96.0%
`
`275
`
`96.8%
`
`0.65
`
`Page 20 of 42
`
`
`
`Baseline Patient Characteristics:
`Vasculopathy (ITT)
`
`SAPIEN
`(n=276)
`
`SAPIEN XT
`(n=284)
`
`Characteristic
`
`n
`
`%
`
`n
`
`%
`
`p-value
`
`186
`
`67.4
`
`186
`
`65.5
`
`0.66
`
`55
`
`76
`
`90
`
`31
`
`24
`
`88
`
`19.4
`
`0.67
`
`26.8
`
`0.92
`
`31.7
`
`0.28
`
`10.9
`
`0.60
`
`8.5
`
`0.39
`
`31.0
`
`0.35
`
`CAD
`
`Previous MI
`
`Previous CABG
`
`58
`
`72
`
`21.0
`
`26.1
`
`Previous PCI
`
`100
`
`36.2
`
`Previous CVA
`
`Previous TIA
`
`Periph vasc disease
`
`35
`
`30
`
`75
`
`12.7
`
`10.9
`
`27.2
`
`Page 21 of 42
`
`
`
`Baseline Patient Characteristics:
`Other Co-morbidities (ITT)
`
`SAPIEN
`(n=276)
`
`SAPIEN XT
`(n=284)
`
`n
`
`%
`
`n
`
`%
`
`p-value
`
`100
`
`36.2
`
`102
`
`35.9
`
`0.99
`
`Characteristic
`
`Diabetes
`
`COPD - Any
`
`COPD - O2 dependent
`
`CKD - creat. ≥ 2mg/dL
`
`Cancer Hx
`
`Previous BAV
`
`72
`
`43
`
`33
`
`99
`
`55
`
`26.1
`
`15.6
`
`12.0
`
`84
`
`38
`
`31
`
`29.6
`
`0.40
`
`13.4
`
`0.47
`
`10.9
`
`0.79
`
`0.93
`
`35.9
`
`100
`
`35.2
`
`19.9
`
`51
`
`18.0
`
`0.59
`
`Atrial fibrillation
`
`112
`
`40.6
`
`104
`
`36.6
`
`0.34
`
`Permanent pacemaker
`
`47
`
`17.0
`
`59
`
`20.8
`
`0.28
`
`Page 22 of 42
`
`
`
`Baseline Patient Characteristics:
`Inoperable Co-morbidities (ITT)
`
`SAPIEN
`(n=276)
`
`SAPIEN XT
`(n=284)
`
`Characteristic
`
`COPD - Inoperable
`
`Dementia
`
`Liver disease
`
`Porcelain aorta
`
`Chest wall radiation
`
`Chest wall deformity
`
`n
`
`22
`
`12
`
`13
`
`11
`
`9
`
`10
`
`%
`
`8.0
`
`4.3
`
`4.7
`
`4.0
`
`3.3
`
`3.6
`
`n
`
`28
`
`22
`
`12
`
`19
`
`13
`
`10
`
`%
`
`9.9
`
`7.7
`
`4.2
`
`6.7
`
`4.6
`
`3.5
`
`p-value
`
`0.46
`
`0.11
`
`0.84
`
`0.19
`
`0.52
`
`0.99
`
`Frailty
`
`166
`
`60.1
`
`168
`
`59.2
`
`0.86
`
`Pulmonary HTN
`
`57
`
`20.7
`
`72
`
`25.4
`
`0.19
`
`Page 23 of 42
`
`
`
`Baseline Echocardiography (ITT)
`
`Characteristic
`
`AV area - cm²
`(mean ± SD)
`
`AV gradient - mmHg
`(mean ± SD)
`
`SAPIEN
`(n=276)
`
`SAPIEN XT
`(n=284)
`
`n
`
`n
`
`p-value
`
`229
`
`0.6 ± 0.2
`
`256
`
`0.6 ± 0.2
`
`0.59
`
`237
`
`45.5 ± 14.4
`
`263
`
`45.2 ± 14.0
`
`0.85
`
`LV ejection fraction (%)
`
`178
`
`53.0 ± 13.7
`
`197
`
`52.4 ± 13.4
`
`0.68
`
`Mod-severe MR (%)
`
`72
`
`31.3
`
`71
`
`28.1
`
`0.49
`
`Page 24 of 42
`
`
`
`Study Flow – Inoperable
`Vital Status
`
`n=560
`Randomized Inoperable
`
`n=276
`SAPIEN
`
`n=284
`SAPIEN XT
`
`6 = Withdrawal = 2
`
`0 = LTFU = 0
`
`17 = Death = 13
`
`11 = Withdrawal = 3
`
`0 = LTFU = 0
`
`65 = Death = 62
`
`269/269 or 100% followed
`at 30 Days
`
`219/219 or 100% followed
`at 1 Year
`
`253/253 or 100% followed
`at 30 Days
`
`200/200 or 100% followed
`at 1 Year
`
`Page 25 of 42
`
`
`
`Procedural Factors (AT)
`
`Events
`
`SAPIEN
`(n=271)
`
`SAPIEN XT
`(n=282)
`
`n
`
`n
`
`p-value
`
`Procedure time (mins)
`
`271 109.6 ± 57.2
`
`282 101.0 ± 43.2
`
`0.18
`
`Anesthesia time (mins)
`
`266 212.0 ± 75.7
`
`277 197.6 ± 60.8
`
`0.02
`
`≥ 2 valves implanted
`
`10
`
`Valve embolization
`
`Aborted procedure
`
`Aortic rupture
`
`Aortic dissection
`
`IABP during procedure
`
`Cardiopulmonary Bypass
`
`0
`
`8
`
`2
`
`1
`
`6
`
`5
`
`3.7
`
`0
`
`3.0
`
`0.7
`
`0.4
`
`2.2
`
`1.8
`
`3
`
`0
`
`2
`
`1
`
`1
`
`1
`
`5
`
`1.1
`
`0
`
`0.7
`
`0.4
`
`0.4
`
`0.4
`
`1.8
`
`0.05
`
`NA
`
`0.06
`
`0.62
`
`0.99
`
`0.06
`
`0.99
`
`Page 26 of 42
`
`
`
`Primary Endpoint Events:
`At 30 Days (ITT)
`
`Events
`
`Death:
`
`All-Cause
`
`Cardiovascular
`
`Stroke:
`
`Disabling
`
`All
`
`All + TIA
`
`Death (all-cause)
`and Stroke (disabling)
`
`Re-hospitalizations
`
`Death (all-cause),Stroke
`(disabling), and Re-hosp
`
`*p-values are KM - Log Rank
`
`n
`
`14
`
`9
`
`8
`
`11
`
`13
`
`19
`
`27
`
`42
`
`SAPIEN
`(n=276)
`
`SAPIEN XT
`(n=284)
`
`%
`
`5.1
`
`3.3
`
`3.0
`
`4.1
`
`4.8
`
`6.9
`
`10.2
`
`15.3
`
`n
`
`10
`
`5
`
`9
`
`12
`
`12
`
`18
`
`32
`
`48
`
`%
`
`p-value*
`
`3.5
`
`1.8
`
`3.2
`
`4.3
`
`4.3
`
`6.4
`
`11.6
`
`17.0
`
`0.36
`
`0.26
`
`0.85
`
`0.88
`
`0.78
`
`0.80
`
`0.59
`
`0.60
`
`Page 27 of 42
`
`
`
`Other Clinical Outcomes:
`At 30 Days (ITT)
`
`Events
`
`MI
`
`AKI
`
`New onset AF
`
`New onset LBBB
`
`New Permanent
`Pacemaker
`
`Re-intervention
`
`Endocarditis
`
`SAPIEN
`(n=276)
`
`SAPIEN XT
`(n=284)
`
`n
`
`2
`
`%
`
`0.7
`
`n
`
`5
`
`%
`
`1.8
`
`38
`
`14.2
`
`37
`
`13.3
`
`8
`
`3
`
`16
`
`8
`
`0
`
`2.9
`
`1.3
`
`5.9
`
`2.9
`
`0
`
`4
`
`4
`
`18
`
`7
`
`0
`
`1.4
`
`1.2
`
`6.4
`
`2.5
`
`0
`
`p-value
`
`0.27
`
`0.78
`
`0.38
`
`0.99
`
`0.78
`
`0.75
`
`NA
`
`Page 28 of 42
`
`
`
`Vascular and Bleeding Events:
`At 30 Days (AT)
`
`Events
`
`Vascular:
`
`Major
`
`Minor
`
`Bleeding:
`
`Disabling
`
`Major
`
`Patients with Transfusions
`
`SAPIEN
`(n=271)
`
`SAPIEN XT
`(n=282)
`
`n
`
`%
`
`n
`
`%
`
`p-value
`
`42
`
`20
`
`34
`
`44
`
`6
`
`15.5
`
`7.4
`
`12.6
`
`16.4
`
`2.2
`
`27
`
`14
`
`22
`
`44
`
`7
`
`9.6
`
`5.0
`
`7.8
`
`15.7
`
`2.5
`
`0.04
`
`0.23
`
`0.06
`
`0.84
`
`0.84
`
`Page 29 of 42
`
`
`
`Vascular Complication Categories:
`At 30 Days (AT)
`
`SAPIEN
`(n=271)
`
`SAPIEN XT
`(n=282)
`
`Events
`
`Perforation
`
`Dissection
`
`Hematoma
`
`n
`
`13
`
`25
`
`16
`
`%
`
`4.8
`
`9.2
`
`5.9
`
`n
`
`2
`
`12
`
`10
`
`%
`
`0.4
`
`4.3
`
`3.6
`
`p-value
`
`0.003
`
`0.03
`
`0.23
`
`Page 30 of 42
`
`
`
`23.7%
`
`22.5%
`
`12
`
`137
`
`147
`
`HR [95% CI] =
`0.93 [0.66, 1.33]
`p (log rank) = 0.706
`
`All-Cause Mortality (ITT)
`
`SAPIEN
`
`SAPIEN XT
`
`5.1%
`3.5%
`
`70%
`
`60%
`
`50%
`
`40%
`
`30%
`
`20%
`
`10%
`
`0%
`
`All-Cause Mortality
`
`0
`No. at Risk
`
`SAPIEN 276
`
`SAPIEN XT 284
`
`3
`
`246
`
`255
`
`6
`Months post Randomization
`
`227
`
`242
`
`9
`
`213
`
`232
`
`Page 31 of 42
`
`
`
`4.6%
`4.5%
`
`12
`
`134
`
`145
`
`HR [95% CI] =
`0.96 [0.43, 2.14]
`p (log rank) = 0.926
`
`Disabling Stroke (ITT)
`
`SAPIEN
`
`SAPIEN XT
`
`3.2%
`3.0%
`
`70%
`
`60%
`
`50%
`
`40%
`
`30%
`
`20%
`
`10%
`
`0%
`
`Disabling Stroke
`
`0
`No. at Risk
`
`SAPIEN 276
`
`SAPIEN XT 284
`
`3
`
`241
`
`250
`
`6
`Months post Randomization
`
`223
`
`238
`
`9
`
`209
`
`227
`
`Page 32 of 42
`
`
`
`19.0%
`
`17.4%
`
`12
`
`120
`
`123
`
`HR [95% CI] =
`0.92 [0.62, 1.38]
`p (log rank) = 0.691
`
`Re-hospitalization (ITT)
`
`SAPIEN
`
`SAPIEN XT
`
`11.6%
`10.2%
`
`70%
`
`60%
`
`50%
`
`40%
`
`30%
`
`20%
`
`10%
`
`0%
`
`Re-hospitalization
`
`0
`No. at Risk
`
`SAPIEN 276
`
`SAPIEN XT 284
`
`3
`
`209
`
`225
`
`6
`Months post Randomization
`
`196
`
`208
`
`9
`
`184
`
`200
`
`Page 33 of 42
`
`
`
`34.7%
`
`33.9%
`
`12
`
`118
`
`122
`
`All-Cause Mortality, Disabling Stroke,
`and Re-hospitalization (ITT)
`
`HR [95% CI] =
`0.97 [0.73, 1.30]
`p (log rank) = 0.863
`p (non-inferiority) = 0.0034*
`
`SAPIEN
`
`SAPIEN XT
`
`17.0%
`
`15.3%
`
`70%
`
`60%
`
`50%
`
`40%
`
`30%
`
`20%
`
`10%
`
`0%
`
`All-Cause Mortality, Disabling Stroke, and Re-hosp.
`
`0
`No. at Risk
`
`SAPIEN 276
`
`SAPIEN XT 284
`
`3
`
`207
`
`221
`
`6
`Months post Randomization
`
`194
`
`205
`
`9
`
`182
`
`197
`
`*Preliminary based upon 100% CEC adjudication at 30 days and 89% CEC adjudication at 1 year.
`
`Page 34 of 42
`
`
`
`NYHA Class Survivors (ITT)
`
`100%
`
`%
`
`80%
`
`60%
`
`40%
`
`20%
`
`0%
`
`p = NS
`
`p = NS
`
`p = NS
`
`p = NS
`
`24%
`
`15%
`22%
`
`16%
`
`12%
`
`12%
`
`96%
`
`97%
`
`IV
`
`III
`
`II
`
`I
`
`SAPIEN SAPIEN
`XT
`
`SAPIEN SAPIEN
`XT
`
`SAPIEN SAPIEN
`XT
`
`276
`
`284
`
`Baseline
`
`249
`
`263
`
`30 Days
`
`207
`
`217
`
`6 Months
`
`SAPIEN SAPIEN
`XT
`
`186
`
`199
`
`1 Year
`
`Page 35 of 42
`
`
`
`Echocardiographic Findings:
`Aortic Valve Area (AT, Valve Implanted)
`
`Error bars at 1 standard deviation
`
`1.6
`
`1.5
`
`p = NS
`
`1.5
`
`1.4
`
`p = NS
`
`2.5
`
`SAPIEN
`
`2
`
`SAPIEN XT
`
`0.6
`
`0.6
`
`p = NS
`
`1.5
`
`1
`
`0.5
`
`0
`
`Valve Area (cm²)
`
`Baseline
`
`30 Days
`
`1 Year
`
`No. of Echos
`
`SAPIEN
`
`SAPIEN XT
`
`229
`
`256
`
`215
`
`233
`
`112
`
`117
`
`Page 36 of 42
`
`
`
`Echocardiographic Findings:
`Mean & Peak Gradients (AT, Valve Implant)
`
`Peak Gradient - SAPIEN
`
`Peak Gradient - SAPIEN XT
`
`Mean Gradient - SAPIEN
`
`Mean Gradient - SAPIEN XT
`
`20.7
`
`19.9
`10.4
`
`10.0
`
`30 Days
`
`224
`
`237
`
`23.8
`
`21.4
`
`11.9
`10.8
`
`1 Year
`
`113
`
`118
`
`78.9
`
`78.2
`
`45.5
`
`45.2
`
`90
`
`80
`
`70
`
`60
`
`50
`
`40
`
`30
`
`20
`
`10
`
`0
`
`Gradient (mmHg)
`
`No. of Echos
`
`SAPIEN
`
`SAPIEN XT
`
`Baseline
`
`237
`
`263
`
`Page 37 of 42
`
`
`
`Paravalvular Aortic Regurgitation
`(AT, Valve Implant)
`
`None
`
`Trace Mild Moderate
`
`Severe
`
`p = 0.12
`
`p = 0.20
`
`100%
`
`80%
`
`16.9%
`
`24.2%
`
`20.9%
`
`60%
`
`44.4%
`
`37.7%
`
`40.9%
`
`40%
`
`29.2%
`
`30.8%
`
`20%
`
`38.6%
`
`38.2%
`
`38.2%
`
`40.0%
`
`0%
`
`SAPIEN SAPIEN XT
`
`SAPIEN SAPIEN XT
`
`30 Days
`
`1 Year
`
`No. of Echos
`
`225
`
`236
`
`110
`
`120
`
`Percent of evaluable echos
`
`Page 38 of 42
`
`
`
`Conclusions (1)
`
`In the inoperable cohort of the PARTNER II trial,
`comparing the SAPIEN versus the SAPIEN XT
`THV systems…
`
`• During the TAVR procedure,
`
`− SAPIENT XT treatment was associated with reductions
`in anesthesia time (p = 0.02), multiple valve implants
`(p = 0.05), aborted procedures (p = 0.06), and the
`need for IABP hemodynamic support (p = 0.06).
`
`Page 39 of 42
`
`
`
`Conclusions (2)
`
`In the inoperable cohort of the PARTNER II trial,
`comparing the SAPIEN versus the SAPIEN XT
`THV systems…
`
`• At 30 days,
`– All-cause mortality and disabling strokes were similar
`(Mortality: SAPIEN 5.1% vs. SAPIEN XT 3.5%;
`Strokes: SAPIEN 3.0% vs. SAPIEN XT 3.2%)
`– Major vascular complications were reduced after
`SAPIENT XT (from 15.5% to 9.6%, p = 0.04), including
`perforations, dissections, and hematomas
`– All other clinical endpoints were similar
`
`Page 40 of 42
`
`
`
`Conclusions (3)
`
`In the inoperable cohort of the PARTNER II trial,
`comparing the SAPIEN versus the SAPIEN XT
`THV systems…
`
`• At 1 year,
`– All-cause mortality, disabling strokes, and re-
`hospitalizations were similar, including the non-
`hierarchical composite primary endpoint
`(SAPIEN XT 33.9% vs. SAPIEN 34.7%, the
`non-inferiority p-value = 0.0034)
`– Improvement in NYHA class was similar
`– Echo valve performance (EOA and gradients) was
`similar
`
`Page 41 of 42
`
`
`
`Implications
`
`In the inoperable cohort of The PARTNER II Trial,
`the new lower profile SAPIEN XT THV system was
`associated with…
`
`
`
`• Improved procedural outcomes
`• Similar low 30-day mortality and strokes
`• Reduced vascular complications
`• Similar 1-year major clinical events and
` valve performance
`
`Therefore, SAPIEN XT represents a worthwhile
`advance with incremental clinical value and is the
`preferred balloon-expandable THV system.
`
`Page 42 of 42
`
`
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