Transcript The Detrimental Impact of Chronic Renal Insufficiency

Health Related Quality of Life after
Transcatheter Aortic Valve Implantation
vs. Non-Surgical Therapy among
Inoperable Patients with Severe Aortic Stenosis:
Results from the PARTNER Trial (Cohort B)
David J. Cohen, M.D., M.Sc.
On Behalf of the PARTNER Investigators
Saint Luke’s Mid America Heart and Vascular Institute
University of Missouri-Kansas City
Kansas City, Missouri
Disclosures
The PARTNER trial was funded by a research
grant from Edwards Lifesciences, Inc.
Background
• Over the past decade, transcatheter aortic valve implantation
(TAVI) has been developed as a less-invasive alternative to
surgical valve replacement for high-risk patients with severe
aortic stenosis
• Recently, the PARTNER trial demonstrated that for patients
who are not suitable candidates for surgery, TAVI led to a
significant reduction in all-cause mortality (20% ARR at 1-year,
p<0.001) but also an but also an increase in the incidence of
major strokes and vascular complications
• Given the advanced age and multiple comorbid conditions in
these inoperable patients, improvements in quality of life may
be an equally important therapeutic goal as improved survival
Study Objectives
1. To compare health-related quality of life outcomes
among inoperable patients with severe aortic stenosis,
treated with either TAVI or standard therapy
2. To examine whether the HRQOL benefits of TAVI are
influenced by pre-specified patient characteristics
3. To provide key “input” data for ongoing economic
evaluation of TAVI for the inoperable patient population
Patient Population
Inclusion Criteria
• Severe, symptomatic AS (AVA <0.8 cm2, mean gradient > 40
mmHg, or peak aortic jet velocity >4.0 m/sec)
• “Inoperable”  Predicted risk of mortality or irreversible
morbidity >50% as determined by 2 independent surgeons
Exclusion Criteria (Selected)
•
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•
•
•
•
LVEF < 20%
Severe (>3+) MR or AR
Untreated CAD requiring revascularization
Serum creatinine > 3.0 mg/dl or hemodialysis
Recent MI (1 month), stroke or TIA (6 months)
Life expectancy < 12 months
Methods: Quality of Life
Instrument
Kansas City
Cardiomyopathy
Questionnaire (KCCQ)
Description/Role
• Heart Failure-specific QOL
• Domains: Symptoms, Physical
Limitations, Quality of Life, Social
Limitations
• Scores: 0-100 (higher = better)
• General physical and mental health
SF-12
• 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
questionnaires at baseline, 1, 6, & 12 months
KCCQ:
Development and Validation
• 23 items that measure 5 clinically relevant domains
of health status from the patient’s perspective
• Symptoms
• Quality of Life
• Self-Efficacy
Physical Limitation
Social Limitation
• Individual scales combined into an 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
Statistical Analysis
• Primary QOL Endpoint = KCCQ Overall Summary
Score
• All other QOL scales considered secondary
endpoints
• Scores at each follow-up time point compared
between groups by ANCOVA, adjusting for baseline
• Longitudinal analyses performed using random
effect growth curve models, adjusting for treatment
group (TAVI vs. control), time (linear, quadratic, cubic
effects), and all potential 2-way and 3-way
interactions
Baseline Characteristics
TAVI
Control
(N=179)
(N=179)
Age (yrs)
83  9
83  8
Female gender
54.2%
54.1%
STS Risk Score
11.2  5.8
12.2  6.1
21.2%
24.7%
Prior MI
18.6%
26.4%
Prior CABG
37.4%
45.6%
Cerebrovascular Dz
27.4%
27.5%
COPD (O2 dependent)
21.2%
25.7%
Creatinine > 2.0 mg/dl
5.6%
9.6%
Frailty
18.1%
28.0%
STS > 15%
P=NS for all comparisons
Baseline QOL
TAVI
Control
(N=179)
(N=179)
36.2  20.5
34.4  20.1
75-100 (~NYHA I)
4.1%
3.8%
60-74 (~NYHA II)
10.6%
7.0%
45-59 (~NYHA III)
15.9%
17.8%
0-45 (~NYHA IV)
69.4%
71.3%
SF-12 Physical
28.2  7.7
27.7  6.9
SF-12 Mental
44.5  12.2
45.2  11.0
EQ-5D Utilities
0.59  0.23
0.57  0.23
KCCQ Overall Summary
P=NS for all comparisons
KCCQ-Summary:
Significant Improvement *
100%
P <0.001 for all time points
TAVI
Control
78.5%
80%
77.3%
65.3%
60%
40%
40.3%
43.5%
34.3%
20%
0%
1 month
6 months
12 months
* Improvement ≥ 10 points vs. baseline among patients with available QOL data
KCCQ-Summary:
Favorable Outcome *
80%
P <0.001 for all time points
TAVI
60%
Control
53.6%
53.1%
47.5%
40%
30.3%
23.0%
20%
13.8%
0%
1 month
6 months
12 months
*Favorable Outcome = Alive and KCCQ-Summary Score improved ≥ 10 points vs. baseline
KCCQ-Summary:
Excellent Outcome *
80%
P <0.001 for all time points
TAVI
Control
60%
45.3%
43.6%
38.0%
40%
20%
19.1%
16.1%
9.2%
0%
1 month
6 months
12 months
* Excellent Outcome = Alive and KCCQ-Summary Score improved ≥ 20 points vs. baseline
Summary
• Among patients with severe, inoperable aortic
stenosis, TAVI– as compared with non-operative
therapy (including BAV in ~80%)-- led to substantial
and sustained improvement across a broad range of
health status and quality of life domains
• The extent of benefit was large for both diseasespecific and general QOL and was consistent across
all pre-specified subgroups
• KCCQ Summary Score 20-25 points (~2-level NHYA Class
improvement on average)
• SF-12 Physical Component 5 points (~10 year reduction in
effective age)
Summary- 2
• When QOL was considered along with survival, the
number needed to treat to obtain an excellent outcome
(i.e., 1-year survival with at least a 20 point improvement
in the KCCQ ) was ~3
Clinical Implications:
These findings add further support to the concept
that TAVI should be considered an emerging
standard of care for patients with severe aortic
stenosis who are not candidates for surgical AVR
Study Administration
• Co-Principal Investigators

Martin B. Leon, Craig R. Smith
Columbia University Med Center
• Executive Committee

Martin B. Leon, Michael Mack,
D. Craig Miller, Jeffrey W. Moses,
Craig R. Smith, Lars G. Svensson,
E. Murat Tuzcu, John G. Webb
• Data & Safety Monitoring Board

Chairman: Joseph P. Carrozza
Tufts University School of Med
• Clinical Events Committee

Chairman: John L. Petersen
Duke University Med Center
• Echo Core Laboratory

Chairman: Pamela C. Douglas
Duke University Med Center
• Quality of Life and Cost
Effectiveness Assessments
 Chairman: David J. Cohen
Mid-America Heart Inst, KC
• Independent Biostatistical Core
Laboratory
 Chairman: Stuart Pocock
London School of Hygiene &
Tropical Medicine
 William N. Anderson
• Publications Committee
 Co-Chairman: Jeffrey W. Moses,
Lars G. Svensson
• Sponsor
 Edwards Lifesciences:
Jodi J. Akin
Enrollment by Site - Inoperable
Cedars-Sinai Medical Ctr
36
Los Angeles, CA
G. Fontana, R. Makkar
Columbia University
33
21
43
Cleveland, OH
L. Svensson, M. Tuzcu
Barnes-Jewish Hospital
12
St. Paul's Hospital
22
Vancouver, BC, Canada
A. Cheung, J. Webb
50
District of Columbia
P. Corso, A. Pichard
Cleveland Clinic Found
15
St. Louis, MO
R. Damiano, J, Lasala
Atlanta, GA
P. Block, R. Guyton
Washington Hospital Ctr
University of Miami
Miami, FL
W. O’Neill, D. Williams
Dallas, TX
D. Brown, M. Mack
Emory University
21
Philadelphia, PA
J. Bavaria, H. Herrmann
New York City, NY
M. Leon, C. Smith
Medical City Dallas
University of Pennsylvania
Stanford University
6
Palo Alto, CA
C. Miller, A. Yeung
45
Northwestern University
Chicago, IL
C. Davidson, P. McCarthy
6
Enrollment by Site - Inoperable
St. Luke’s Hospital
Kansas City, MO
K. Allen, D. Cohen
5
Herzzentrum Leipzig
Leipzig, Germany
F. Mohr, G. Schuler
2
Mass General Hospital
Boston, MA
I. Palacios, G. Vlahakis
2
University of Virginia
Charlottesville, VA
I. Kron, S. Lim
0
Mayo Clinic
Rochester, MN
C. Rihal, T. Sundt
7
0
Scripps Clinic
La Jolla, CA
S. Brewster, P. Teirstein
8
Brigham & Women’s Hosp
Boston, MA
M. Davidson, A.
Eisenhauer
0
Univ of Washington
Seattle, WA
M. Reisman, E. Verrier
8
Cornell University
New York City, NY
K. Krieger, C. Wong
Ochsner Foundation
New Orleans, LA
E. Parrino, S. Ramee
0
Intermountain Med Center
Salt Lake City, UT
K. Jones, B. Whisenant
0
Toronto General Hospital
Toronto, Ontario, CA
C. Feindel, E. Horlick
2
Northshore Univ Health Sys
Evanston, IL
J. Alexander, T. Feldman
10
Universitaire de Quebec
Laval, Quebec, CA
D. Doyle, J. Rodes-Cabau
4