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