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)

1
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)
David J. Cohen, M.D., M.Sc. On behalf of The
PARTNER Investigators
Saint Lukes Mid-America Heart Institute Harvard
Clinical Research Institute University of
Missouri-Kansas City Harvard Medical
School Kansas City, Missouri Boston, MA
TCT 2011 San Francisco November 7, 2011
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Disclosures

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

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Background

• 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 patients perspective has not yet been
  reported

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Study 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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PARTNER Study Design
Symptomatic Severe Aortic Stenosis
ASSESSMENT High-Risk AVR Candidate 3,105 Total
Patients Screened
Total 1,057 patients
High-Risk
N 699
2 Parallel Trials Individually Powered
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Methods Quality of Life
Instrument Description/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 Life
Instrument Description/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 Life
Instrument Description/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)
Assessments performed by self-administered questio
nnaires at baseline and at 1, 6, and 12 months
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KCCQ Development and Validation

• 23 items that measure 5 clinically relevant
  domains of health status from the patients
  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. 2000351245-55.
• Soto G, et al. Circulation. 2004110546-51.

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KCCQ Interpretation
Change in KCCQ-Overall Summary Score

• 546 outpts with HF
• KCCQ assessed at baseline and 5 weeks
• Extent of deterioration or improvement assessed
  by physician based on sx and exam and correlated
  with KCCQ-Overall Summary

• Clinically Important Change
• Small 5 points
• Moderate 10 points
• Large 20 points

Large
Medium
Small
Small
Medium
Large
No Change
Deterioration
Improvement
Am Heart J. 2005150707-15.
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Analytic 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 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 Characteristics
TAVR (n 328) AVR(n 300)
Age (yrs) 84 ? 7 84 ? 6
Male gender 57.6 56.7
STS risk score 11.8 ? 3.4 11.5 ? 3.2
Prior MI 27.4 27.7
Prior CABG 42.7 45.0
Cerebrovascular Dz 26.8 24.7
COPD (O2 dependent) 9.1 7.3
Frailty 15.4 17.1
P NS for all comparisons
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Results

• There were highly significant interactions
  between treatment effect and access site for the
  primary endpoint (P 0.001) and multiple
  secondary endpoints (P lt 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)TF
Subgroup
D 9.9P lt 0.001
D -0.5P NS
D -1.2P NS
P-values are for mean treatment effect of TAVR
vs. AVR
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KCCQ SubscalesTF Subgroup
Physical Limitations
Symptom Score
Quality of Life
Social Limitations
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Generic QOL and UtilitiesTF Subgroup
SF-12 Physical
SF-12 Mental
EQ-5D Utilities
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KCCQ Overall Summary (Primary Endpoint)TA
Subgroup
D -5.8P NS
D -7.9P 0.04
D 0.8P NS
P-values are for mean treatment effect of TAVR
vs. AVR
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KCCQ SubscalesTA Subgroup
Physical Limitations
Symptom Score
Quality of Life
Social Limitations
20
Generic QOL and UtilitiesTA Subgroup
SF-12 Physical
SF-12 Mental
EQ-5D Utilities
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KCCQ-Summary Substantial ImprovementTF Subgroup
P NS
P NS
P 0.008
Improvement 20 points vs. baseline among
patients with available QOL data
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KCCQ-Summary Substantial ImprovementTA Subgroup
P NS at all timepoints
Improvement 20 points vs. baseline among
patients with available QOL data
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Sensitivity 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-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-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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Conclusions

• 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
  patients 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