health related quality of life after transcatheter aortic valve implantation vs. non-surgical...
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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 InstituteUniversity of Missouri-Kansas City
Kansas City, Missouri
Disclosures
The PARTNER trial was funded by a research grant from Edwards Lifesciences, Inc.
BackgroundBackground
• 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 ObjectivesStudy 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 PopulationPatient 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)• 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 LifeMethods: Quality of Life
Assessments performed by self-administeredquestionnaires at baseline, 1, 6, & 12 months
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)
KCCQ: KCCQ: Development and ValidationDevelopment and Validation
• 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
• 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 AnalysisStatistical 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 CharacteristicsBaseline Characteristics
TAVI TAVI (N=179)(N=179)
Control 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
STS > 15% 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%
P=NS for all comparisons
Baseline QOLBaseline QOL
TAVI TAVI (N=179)(N=179)
Control Control (N=179)(N=179)
KCCQ Overall Summary 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
P=NS for all comparisons
KCCQ-Summary: KCCQ-Summary: Significant Improvement Significant Improvement **
77.3%78.5%
65.3%
34.3%
43.5%40.3%
0%
20%
40%
60%
80%
100%
1 month 6 months 12 months
TAVI Control
* Improvement ≥ 10 points vs. baseline among patients with available QOL data
P <0.001 for all time points
KCCQ-Summary: KCCQ-Summary: Favorable Outcome Favorable Outcome **
53.6% 53.1%
47.5%
30.3%
23.0%
13.8%
0%
20%
40%
60%
80%
1 month 6 months 12 months
TAVI Control
*Favorable Outcome = Alive and KCCQ-Summary Score improved ≥ 10 points vs. baseline
P <0.001 for all time points
KCCQ-Summary: KCCQ-Summary: Excellent Outcome Excellent Outcome **
43.6% 45.3%
38.0%
19.1%16.1%
9.2%
0%
20%
40%
60%
80%
1 month 6 months 12 months
TAVI Control
* Excellent Outcome = Alive and KCCQ-Summary Score improved ≥ 20 points vs. baseline
P <0.001 for all time points
SummarySummary
• 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 disease-specific 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- 2Summary- 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 These findings add further support to the concept
that TAVI should be considered an emerging that TAVI should be considered an emerging
standard of care for patients with severe aortic standard of care for patients with severe aortic
stenosis who are not candidates for surgical AVRstenosis who are not candidates for surgical AVR
Study AdministrationStudy Administration
• Co-Principal InvestigatorsCo-Principal Investigators Martin B. Leon, Craig R. SmithMartin B. Leon, Craig R. Smith
Columbia University Med Center Columbia University Med Center
• Executive CommitteeExecutive Committee Martin B. Leon, Michael Mack, Martin B. Leon, Michael Mack,
D. Craig Miller, Jeffrey W. Moses, Craig R. D. Craig Miller, Jeffrey W. Moses, Craig R. Smith, Lars G. Svensson, Smith, Lars G. Svensson, E. Murat Tuzcu, John G. Webb E. Murat Tuzcu, John G. Webb
• Data & Safety Monitoring BoardData & Safety Monitoring Board Chairman: Joseph P. CarrozzaChairman: Joseph P. Carrozza
Tufts University School of MedTufts University School of Med
• Clinical Events CommitteeClinical Events Committee Chairman: John L. PetersenChairman: John L. Petersen
Duke University Med CenterDuke University Med Center
• Echo Core LaboratoryEcho Core Laboratory Chairman: Pamela C. Douglas Chairman: Pamela C. Douglas
Duke University Med CenterDuke University Med Center
• Quality of Life and Cost Quality of Life and Cost Effectiveness AssessmentsEffectiveness Assessments
Chairman: David J. CohenChairman: David J. CohenMid-America Heart Inst, KCMid-America Heart Inst, KC
• Independent Biostatistical Core Independent Biostatistical Core LaboratoryLaboratory
Chairman: Stuart PocockLondon School of Hygiene &Tropical Medicine
William N. Anderson
• Publications CommitteePublications Committee Co-Chairman: Jeffrey W. Moses, Co-Chairman: Jeffrey W. Moses,
Lars G. SvenssonLars G. Svensson
• Sponsor Sponsor Edwards Lifesciences: Edwards Lifesciences:
Jodi J. AkinJodi J. Akin
Enrollment by Site - InoperableEnrollment by Site - Inoperable
Cedars-Sinai Medical CtrCedars-Sinai Medical Ctr Los Angeles, CA G. Fontana, R. Makkar
36
Columbia University Columbia University New York City, NY M. Leon, C. Smith
33
Medical City DallasMedical City Dallas Dallas, TX D. Brown, M. Mack
21
Emory UniversityEmory University Atlanta, GA P. Block, R. Guyton
43
Washington Hospital CtrWashington Hospital Ctr District of Columbia P. Corso, A. Pichard
50
Cleveland Clinic FoundCleveland Clinic Found Cleveland, OH L. Svensson, M. Tuzcu
45
University of PennsylvaniaUniversity of Pennsylvania Philadelphia, PA J. Bavaria, H. Herrmann
21
University of MiamiUniversity of Miami Miami, FL W. O’Neill, D. Williams
15
Barnes-Jewish HospitalBarnes-Jewish Hospital St. Louis, MO R. Damiano, J, Lasala
12
St. Paul's HospitalSt. Paul's Hospital Vancouver, BC, Canada A. Cheung, J. Webb
22
Stanford UniversityStanford University Palo Alto, CA C. Miller, A. Yeung
6
Northwestern UniversityNorthwestern University Chicago, IL C. Davidson, P. McCarthy
6
St. Luke’s HospitalSt. Luke’s Hospital Kansas City, MO K. Allen, D. Cohen
5
Mass General HospitalMass General Hospital Boston, MA I. Palacios, G. Vlahakis
2
Mayo ClinicMayo Clinic Rochester, MN C. Rihal, T. Sundt
7
Scripps Clinic Scripps Clinic La Jolla, CA S. Brewster, P. Teirstein
8
Univ of WashingtonUniv of Washington Seattle, WA M. Reisman, E. Verrier
8
Northshore Univ Health SysNorthshore Univ Health Sys Evanston, IL J. Alexander, T. Feldman
10
Universitaire de QuebecUniversitaire de Quebec Laval, Quebec, CA D. Doyle, J. Rodes-Cabau
4
Herzzentrum LeipzigHerzzentrum Leipzig Leipzig, Germany F. Mohr, G. Schuler
2
University of Virginia University of Virginia Charlottesville, VA I. Kron, S. Lim
0
Brigham & Women’s HospBrigham & Women’s Hosp Boston, MA M. Davidson, A. Eisenhauer
0
Cornell UniversityCornell University New York City, NY K. Krieger, C. Wong
0
Ochsner FoundationOchsner Foundation New Orleans, LA E. Parrino, S. Ramee
0
Intermountain Med CenterIntermountain Med Center Salt Lake City, UT K. Jones, B. Whisenant
0
Toronto General HospitalToronto General Hospital Toronto, Ontario, CA C. Feindel, E. Horlick
2
Enrollment by Site - InoperableEnrollment by Site - Inoperable