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Health-Related Quality of Life After Transcatheter vs. Surgical Aortic Valve Replacement in High-Risk Patients With Severe Aortic Stenosis Results From The PARTNER Trial (Cohort A) TCT 2011 | San Francisco | November 7, 2011 David J. Cohen, M.D., M.Sc. On behalf of The PARTNER Investigators Saint Luke’s Mid-America Heart Institute Harvard Clinical Research Institute University of Missouri-Kansas City Harvard Medical School Kansas City, Missouri Boston, MA

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Page 1: Health-Related Quality of Life After Transcatheter vs. Surgical Aortic Valve Replacement in High-Risk Patients With Severe Aortic Stenosis Results From

Health-Related Quality of Life After Transcatheter vs. Surgical Aortic Valve Replacement in High-Risk Patients With Severe Aortic Stenosis Results From The PARTNER Trial (Cohort A)

TCT 2011 | San Francisco | November 7, 2011

David J. Cohen, M.D., M.Sc. On behalf of The PARTNER Investigators

Saint Luke’s Mid-America Heart Institute Harvard Clinical Research InstituteUniversity of Missouri-Kansas City Harvard Medical SchoolKansas City, Missouri Boston, MA

Page 2: Health-Related Quality of Life After Transcatheter vs. Surgical Aortic Valve Replacement in High-Risk Patients With Severe Aortic Stenosis Results From

Disclosures

The PARTNER Trial was funded by a research grant from Edwards Lifesciences, Inc.

Page 3: Health-Related Quality of Life After Transcatheter vs. Surgical Aortic Valve Replacement in High-Risk Patients With Severe Aortic Stenosis Results From

BackgroundBackground

• Transcatheter aortic valve replacement (TAVR) has been developed as a less invasive alternative to surgical valve replacement for high-risk patients with severe aortic stenosis

• In PARTNER Cohort A, TAVR was found to be non-inferior to surgical AVR for the primary endpoint of 1-year mortality among patients at high surgical risk

• There were differences in procedure-related complications and valve performance at 1 year – with some endpoints favoring TAVR and others favoring surgical AVR

• The overall impact of these alternative treatments on health-related quality of life from the patient’s perspective has not yet been reported

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Page 4: Health-Related Quality of Life After Transcatheter vs. Surgical Aortic Valve Replacement in High-Risk Patients With Severe Aortic Stenosis Results From

Study ObjectivesStudy Objectives

1. Compare health-related quality of life outcomes among patients with severe aortic stenosis and high surgical risk treated with either TAVR or surgical AVR

2. Determine whether the QOL benefits of TAVR vs. AVR

vary over time

3. Examine whether the QOL benefits of TAVR vs. AVR differ according to access site or other patient characteristics

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Page 5: Health-Related Quality of Life After Transcatheter vs. Surgical Aortic Valve Replacement in High-Risk Patients With Severe Aortic Stenosis Results From

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 AVRAVR VS

VS

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

Page 6: Health-Related Quality of Life After Transcatheter vs. Surgical Aortic Valve Replacement in High-Risk Patients With Severe Aortic Stenosis Results From

Methods: Quality of LifeMethods: Quality of Life

InstrumentInstrument Description/RoleDescription/Role

Kansas City Cardiomyopathy Questionnaire (KCCQ)

• Heart failure-specific QOL

• Domains: symptoms, physical limitations, quality of life, social limitations

• Scores: 0-100 (higher = better)

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Page 7: Health-Related Quality of Life After Transcatheter vs. Surgical Aortic Valve Replacement in High-Risk Patients With Severe Aortic Stenosis Results From

Methods: Quality of LifeMethods: Quality of Life

InstrumentInstrument Description/RoleDescription/Role

Kansas City Cardiomyopathy Questionnaire (KCCQ)

• Heart failure-specific QOL

• Domains: symptoms, physical limitations, quality of life, social limitations

• Scores: 0-100 (higher = better)

SF-12 • General physical and mental health

• Scores standardized such that mean = 50, standard deviation = 10 (higher = better)

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Page 8: Health-Related Quality of Life After Transcatheter vs. Surgical Aortic Valve Replacement in High-Risk Patients With Severe Aortic Stenosis Results From

Methods: Quality of LifeMethods: Quality of Life

Assessments performed by self-administeredquestionnaires at baseline and at 1, 6, and 12 months

InstrumentInstrument Description/RoleDescription/Role

Kansas City Cardiomyopathy Questionnaire (KCCQ)

• Heart failure-specific QOL

• Domains: symptoms, physical limitations, quality of life, social limitations

• Scores: 0-100 (higher = better)

SF-12 • General physical and mental health

• Scores standardized such that mean = 50, standard deviation = 10 (higher = better)

EQ-5D (EuroQOL) • Generic instrument for assessment of utilities and QALYs

• Scores: 0-1 (0 = death; 1 = perfect health)

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Page 9: Health-Related Quality of Life After Transcatheter vs. Surgical Aortic Valve Replacement in High-Risk Patients With Severe Aortic Stenosis Results From

KCCQ: Development and KCCQ: Development and ValidationValidation

• 23 items that measure 5 clinically relevant domains of health status from the patient’s perspective– Symptoms Physical limitation

– Quality of life Social limitation

– Self-efficacy

• Extensive validation and reliability testing

• Individual scales combined into a global summary scale (KCCQ Overall Summary)– Independently predictive of mortality and cost among patients

with HF

Green CP, et al. JACC. 2000;35:1245-55.Soto G, et al. Circulation. 2004;110:546-51.9

Page 10: Health-Related Quality of Life After Transcatheter vs. Surgical Aortic Valve Replacement in High-Risk Patients With Severe Aortic Stenosis Results From

KCCQ: InterpretationKCCQ: Interpretation

Am Heart J. 2005;150:707-15.

Large Medium Small

Deterioration

No Change

• 546 outpts with HF546 outpts with HF

• KCCQ assessed at KCCQ assessed at baseline and 5 weeksbaseline and 5 weeks

• Extent of deterioration Extent of deterioration or improvement or improvement assessed by physician assessed by physician based on sx and exam based on sx and exam and correlated with and correlated with KCCQ-Overall KCCQ-Overall SummarySummary

Change in KCCQ-Overall Summary Score

Small Medium Large

Improvement

Clinically Important Change • Small = 5 points

• Moderate = 10 points

• Large = 20 points

Clinically Important Change • Small = 5 points

• Moderate = 10 points

• Large = 20 points

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Page 11: Health-Related Quality of Life After Transcatheter vs. Surgical Aortic Valve Replacement in High-Risk Patients With Severe Aortic Stenosis Results From

Analytic ApproachAnalytic Approach

Analytic Population

• All patients with baseline QOL assessment, analyzed by assigned treatment (ITT)

Primary QOL Endpoint

• KCCQ Overall Summary Score

• All other QOL scales considered secondary endpoints

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Page 12: Health-Related Quality of Life After Transcatheter vs. Surgical Aortic Valve Replacement in High-Risk Patients With Severe Aortic Stenosis Results From

Statistical MethodsStatistical Methods

• Scores at each time point compared within treatment group using paired t-tests

• Scores between groups compared using random effect growth curve models, adjusted for baseline, age, sex, and access site (TA vs. TF)

• Analytic plan specified that separate analyses would be performed for the TA and TF groups in case of a significant interaction between treatment effect and access site

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Page 13: Health-Related Quality of Life After Transcatheter vs. Surgical Aortic Valve Replacement in High-Risk Patients With Severe Aortic Stenosis Results From

Baseline CharacteristicsBaseline Characteristics

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TAVR TAVR (n = 328)(n = 328)

AVRAVR(n = 300)(n = 300)

Age (yrs)Age (yrs) 84 84 7 7 84 84 6 6

Male genderMale gender 57.6%57.6% 56.7%56.7%

STS risk scoreSTS risk score 11.8 11.8 3.4 3.4 11.5 11.5 3.2 3.2

Prior MIPrior MI 27.4%27.4% 27.7%27.7%

Prior CABGPrior CABG 42.7%42.7% 45.0%45.0%

Cerebrovascular DzCerebrovascular Dz 26.8%26.8% 24.7%24.7%

COPD (OCOPD (O22 dependent) dependent) 9.1%9.1% 7.3%7.3%

FrailtyFrailty 15.4%15.4% 17.1%17.1%

P = NS for all comparisons

Page 14: Health-Related Quality of Life After Transcatheter vs. Surgical Aortic Valve Replacement in High-Risk Patients With Severe Aortic Stenosis Results From

ResultsResults

• There were highly significant interactions between treatment effect and access site for the primary endpoint (P = 0.001) and multiple secondary endpoints (P < 0.01) – mainly at the 1 month and 6 month time points

• Therefore, all QOL analyses were performed separately for TF and TA subgroups

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Page 15: Health-Related Quality of Life After Transcatheter vs. Surgical Aortic Valve Replacement in High-Risk Patients With Severe Aortic Stenosis Results From

KCCQ Overall Summary (Primary Endpoint)KCCQ Overall Summary (Primary Endpoint)TF SubgroupTF Subgroup

15 P-values are for mean treatment effect of TAVR vs. AVR

= 9.9P < 0.001

= -0.5P = NS

=-1.2P = NS

Page 16: Health-Related Quality of Life After Transcatheter vs. Surgical Aortic Valve Replacement in High-Risk Patients With Severe Aortic Stenosis Results From

KCCQ SubscalesKCCQ SubscalesTF SubgroupTF Subgroup

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Physical Limitations Symptom Score

Quality of Life Social Limitations

= 10.9P = 0.001

= -0.5P = NS

= 2.3P = NS

= 6.6P = 0.006

= -2.1P = NS

= -1.1P = NS

= 9.8P < 0.001

= 0.3P = NS

= -1.9P = NS

= 10.6P = 0.006

= -2.9P = NS

= -2.9P = NS

Page 17: Health-Related Quality of Life After Transcatheter vs. Surgical Aortic Valve Replacement in High-Risk Patients With Severe Aortic Stenosis Results From

Generic QOL and UtilitiesGeneric QOL and UtilitiesTF SubgroupTF Subgroup

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SF-12 Physical SF-12 Mental

EQ-5D Utilities

= 2.0P = 0.04

= -0.9P = NS

= -0.4P = NS

= 0.061P = 0.008

= 0.012P = NS

= 0.028P = NS

= 5.4P < 0.001

= 1.2P = NS

= 0.4P = NS

Page 18: Health-Related Quality of Life After Transcatheter vs. Surgical Aortic Valve Replacement in High-Risk Patients With Severe Aortic Stenosis Results From

KCCQ Overall Summary (Primary Endpoint)KCCQ Overall Summary (Primary Endpoint)TA SubgroupTA Subgroup

18 P-values are for mean treatment effect of TAVR vs. AVR

= -5.8P = NS

= -7.9P = 0.04

= 0.8P = NS

Page 19: Health-Related Quality of Life After Transcatheter vs. Surgical Aortic Valve Replacement in High-Risk Patients With Severe Aortic Stenosis Results From

KCCQ SubscalesKCCQ SubscalesTA SubgroupTA Subgroup

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Physical Limitations Symptom Score

Quality of Life Social Limitations

= -5.8P = NS

= -9.6P = 0.04

= -4.1P = NS

= -4.7P = NS

= -8.4P = 0.06

= 4.8P = NS

= -5.1P = NS

= -13.2P < 0.001

= -2.3P = NS

= -5.8P = NS

= -3.8P = NS

= 6.1P = NS

Page 20: Health-Related Quality of Life After Transcatheter vs. Surgical Aortic Valve Replacement in High-Risk Patients With Severe Aortic Stenosis Results From

Generic QOL and UtilitiesGeneric QOL and UtilitiesTA SubgroupTA Subgroup

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SF-12 Physical SF-12 Mental

EQ-5D Utilities

= 0.3P = NS

= -3.3P = 0.05

= 0.2P = NS

= -4.3P = 0.02

= -2.5P = NS

= -2.5P = NS

= -0.057P = NS

= -0.065P = 0.05

= -0.051P = NS

Page 21: Health-Related Quality of Life After Transcatheter vs. Surgical Aortic Valve Replacement in High-Risk Patients With Severe Aortic Stenosis Results From

KCCQ-Summary: Substantial Improvement*KCCQ-Summary: Substantial Improvement*TF SubgroupTF Subgroup

* Improvement ≥ 20 points vs. baseline among patients with available QOL data

P = 0.008

P = NSP = NS

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Page 22: Health-Related Quality of Life After Transcatheter vs. Surgical Aortic Valve Replacement in High-Risk Patients With Severe Aortic Stenosis Results From

KCCQ-Summary: Substantial Improvement*KCCQ-Summary: Substantial Improvement*TA SubgroupTA Subgroup

* Improvement ≥ 20 points vs. baseline among patients with available QOL data

P = NS at all timepoints

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Page 23: Health-Related Quality of Life After Transcatheter vs. Surgical Aortic Valve Replacement in High-Risk Patients With Severe Aortic Stenosis Results From

Sensitivity AnalysesSensitivity Analyses

Results similar when:

• Analysis restricted to patients who underwent attempted valve treatment (“As treated” cohort; n = 607)

• “Worst case” values (at the 90th percentile) were imputed to all patients with missing data

• Outcomes analyzed categorically according to either significant improvement (≥ 10-point change from baseline) or a multilevel ordinal outcome

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Page 24: Health-Related Quality of Life After Transcatheter vs. Surgical Aortic Valve Replacement in High-Risk Patients With Severe Aortic Stenosis Results From

Summary-1Summary-1

• Among patients with severe AS who were at high risk for standard valve replacement, both surgical and transcatheter AVR resulted in substantial improvement in disease-specific and generic HRQOL over 1 year follow-up

– KCCQ Summary Scale ~ 25-30 points (MCID = 5)

– SF-12 Physical ~ 6 points (MCID = 2)

– SF-12 Mental ~ 5 points (MCID = 2)

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Page 25: Health-Related Quality of Life After Transcatheter vs. Surgical Aortic Valve Replacement in High-Risk Patients With Severe Aortic Stenosis Results From

Summary-2Summary-2

• Although the extent of improvement at 1 year was similar with TAVR and AVR, there were important differences in the rate and extent of recovery at the earlier time points

• For patients eligible for the TF approach, TAVR resulted in substantial QOL benefits compared with AVR at 1 month with similar QOL at later time points

• For patients eligible only for the TA approach, there was no benefit of TAVR over AVR at any time point, and QOL tended to be better with AVR both at 1 and 6 months

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Page 26: Health-Related Quality of Life After Transcatheter vs. Surgical Aortic Valve Replacement in High-Risk Patients With Severe Aortic Stenosis Results From

ConclusionsConclusions

• Taken together with previous data, these findings demonstrate that for patients suitable for a TF approach, TAVR provides meaningful clinical benefits compared with surgical AVR from the patient’s perspective

• The lack of benefit (and suggestion of worse QOL) among patients ineligible for the TF approach suggests that the TA approach may not be preferable to surgical AVR in such patients

• Whether further experience and refinements in the TA approach can overcome these limitations should be the subject of future investigation

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