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