Скачать презентацию Health-Related Quality of Life After Transcatheter vs Surgical Скачать презентацию Health-Related Quality of Life After Transcatheter vs Surgical

5ab0054ab82190d36d607d04654c0c31.ppt

  • Количество слайдов: 29

Health-Related Quality of Life After Transcatheter vs. Surgical Aortic Valve Replacement in High-Risk Patients 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 Luke’s Mid-America Heart Institute University of Missouri-Kansas City, Missouri Harvard Clinical Research Institute Harvard Medical School Boston, MA TCT 2011 | San Francisco | November 7, 2011

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

Background • Transcatheter aortic valve replacement (TAVR) has been developed as a less invasive 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 healthrelated quality of life from the patient’s perspective has not yet been reported 3

Study Objectives 1. Compare health-related quality of life outcomes among patients with severe aortic 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 4

PARTNER Study Design Symptomatic Severe Aortic Stenosis ASSESSMENT: High-Risk AVR Candidate 3, 105 Total PARTNER Study Design Symptomatic Severe Aortic Stenosis ASSESSMENT: High-Risk AVR Candidate 3, 105 Total Patients Screened Total = 1, 057 patients N = 699 Yes High-Risk ASSESSMENT: Transfemoral Access Transfemoral (TF) 1: 1 Randomization N = 244 TF TAVR V S Transfemoral Access 1: 1 Randomization N = 104 AVR TA TAVR N = 358 ASSESSMENT: No Transapical (TA) N = 248 Inoperable 2 Parallel Trials: Individually Powered Yes 1: 1 Randomization N = 103 N = 179 AVR TF TAVR V S Primary Endpoint: All-Cause Mortality at 1 yr (Non-inferiority) No Not In Study N = 179 V S Standard Therapy Primary Endpoint: All-Cause Mortality Over Length of Trial (Superiority) Co-Primary Endpoint: Composite of All-Cause Mortality and Repeat Hospitalization (Superiority)

Methods: Quality of Life Instrument Kansas City Cardiomyopathy Questionnaire (KCCQ) 6 Description/Role • Heart Methods: Quality of Life Instrument Kansas City Cardiomyopathy Questionnaire (KCCQ) 6 Description/Role • Heart failure-specific QOL • Domains: symptoms, physical limitations, quality of life, social limitations • Scores: 0 -100 (higher = better)

Methods: Quality of Life Instrument Description/Role Kansas City Cardiomyopathy Questionnaire (KCCQ) SF-12 7 • Methods: Quality of Life Instrument Description/Role Kansas City Cardiomyopathy Questionnaire (KCCQ) SF-12 7 • Heart failure-specific QOL • Domains: symptoms, physical limitations, quality of life, social limitations • Scores: 0 -100 (higher = better) • General physical and mental health • Scores standardized such that mean = 50, standard deviation = 10 (higher = better)

Methods: Quality of Life Instrument Description/Role Kansas City Cardiomyopathy Questionnaire (KCCQ) SF-12 • General Methods: Quality of Life Instrument Description/Role Kansas City Cardiomyopathy Questionnaire (KCCQ) SF-12 • General physical and mental health • Scores standardized such that mean = 50, standard deviation = 10 (higher = better) EQ-5 D (Euro. QOL) 8 • Heart failure-specific QOL • Domains: symptoms, physical limitations, quality of life, social limitations • Scores: 0 -100 (higher = better) • Generic instrument for assessment of utilities and QALYs • Scores: 0 -1 (0 = death; 1 = perfect health) Assessments performed by self-administered questionnaires at baseline and at 1, 6, and 12 months

KCCQ: Development and Validation • 23 items that measure 5 clinically relevant domains of 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 • 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 9 Green CP, et al. JACC. 2000; 35: 1245 -55. Soto G, et al. Circulation. 2004; 110: 546 -51.

KCCQ: Interpretation Change in KCCQ-Overall Summary Score • 546 outpts with HF • KCCQ 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 Large Medium Small Deterioration 10 • Small = 5 points Small Medium Large No • Moderate = 10 points Change Improvement • Large = 20 points Am Heart J. 2005; 150: 707 -15.

Analytic Approach Analytic Population • All patients with baseline QOL assessment, analyzed by assigned 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 11

Statistical Methods • Scores at each time point compared within treatment group using paired 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 12

Baseline Characteristics TAVR (n = 328) (n = 300) Age (yrs) 84 7 84 Baseline Characteristics TAVR (n = 328) (n = 300) Age (yrs) 84 7 84 6 Male gender 57. 6% 56. 7% 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 (O 2 dependent) 9. 1% 7. 3% Frailty 15. 4% 17. 1% STS risk score 13 P = NS for all comparisons

QOL Compliance ITT Population (n = 699) 14 (n = 656) (n = 574) QOL Compliance ITT Population (n = 699) 14 (n = 656) (n = 574) (n = 528) * Among pts eligible for QOL assessment

Results • There were highly significant interactions between treatment effect and access site for Results • 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 15

KCCQ Overall Summary (Primary Endpoint) TF Subgroup D = 9. 9 P < 0. KCCQ Overall Summary (Primary Endpoint) TF Subgroup D = 9. 9 P < 0. 001 16 D = -0. 5 P = NS D = -1. 2 P = NS P-values are for mean treatment effect of TAVR vs. AVR

KCCQ Subscales TF Subgroup Physical Limitations D = 10. 9 P = 0. 001 KCCQ Subscales TF Subgroup Physical Limitations D = 10. 9 P = 0. 001 D = -0. 5 P = NS Symptom Score D = 2. 3 P = NS 17 D = -2. 1 P = NS D = -1. 1 P = NS D = -2. 9 P = NS Social Limitations Quality of Life D = 9. 8 P < 0. 001 D = 6. 6 P = 0. 006 D = 0. 3 P = NS D = -1. 9 P = NS D = 10. 6 P = 0. 006

Generic QOL and Utilities TF Subgroup SF-12 Physical D = 2. 0 P = Generic QOL and Utilities TF Subgroup SF-12 Physical D = 2. 0 P = 0. 04 SF-12 Mental D = -0. 4 P = NS D = -0. 9 P = NS D = 5. 4 P < 0. 001 EQ-5 D Utilities D = 0. 061 P = 0. 008 18 D = 0. 012 P = NS D = 0. 028 P = NS D = 1. 2 P = NS D = 0. 4 P = NS

KCCQ Overall Summary (Primary Endpoint) TA Subgroup D = -5. 8 P = NS KCCQ Overall Summary (Primary Endpoint) TA Subgroup D = -5. 8 P = NS 19 D = -7. 9 P = 0. 04 D = 0. 8 P = NS P-values are for mean treatment effect of TAVR vs. AVR

KCCQ Subscales TA Subgroup Physical Limitations D = -5. 8 P = NS D KCCQ Subscales TA Subgroup Physical Limitations D = -5. 8 P = NS D = -9. 6 P = 0. 04 Symptom Score D = -4. 1 P = NS Quality of Life D = -4. 7 P = NS 20 D = -5. 1 P = NS D = -13. 2 P < 0. 001 D = -2. 3 P = NS Social Limitations D = -8. 4 P = 0. 06 D = 4. 8 P = NS D = -5. 8 P = NS D = -3. 8 P = NS D = 6. 1 P = NS

Generic QOL and Utilities TA Subgroup SF-12 Physical D = 0. 3 P = Generic QOL and Utilities TA Subgroup SF-12 Physical D = 0. 3 P = NS SF-12 Mental D = 0. 2 P = NS D = -3. 3 P = 0. 05 D = -4. 3 P = 0. 02 EQ-5 D Utilities D = -0. 057 P = NS 21 D = -0. 065 P = 0. 05 D = -0. 051 P = NS D = -2. 5 P = NS

Overall Clinical Status TF Subgroup P < 0. 001 P = 0. 007 P Overall Clinical Status TF Subgroup P < 0. 001 P = 0. 007 P = NS KCCQ Categories 1 month 22 6 months 1 year *P-values from ordinal logistic regression

Overall Clinical Status TA Subgroup P = NS KCCQ Categories 1 month 23 6 Overall Clinical Status TA Subgroup P = NS KCCQ Categories 1 month 23 6 months 1 year *P-values from ordinal logistic regression

KCCQ-Summary: Substantial Improvement* TF Subgroup P = NS P = 0. 008 24 * KCCQ-Summary: Substantial Improvement* TF Subgroup P = NS P = 0. 008 24 * Improvement ≥ 20 points vs. baseline among patients with available QOL data

KCCQ-Summary: Substantial Improvement* TA Subgroup P = NS at all timepoints 25 * Improvement KCCQ-Summary: Substantial Improvement* TA Subgroup P = NS at all timepoints 25 * Improvement ≥ 20 points vs. baseline among patients with available QOL data

Sensitivity Analyses Results similar when: • Analysis restricted to patients who underwent attempted valve Sensitivity Analyses Results similar when: • Analysis restricted to patients who underwent attempted valve treatment (“As treated” cohort; n = 607) • “Worst case” values (at the 90 th 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 26

Summary-1 • Among patients with severe AS who were at high risk for standard 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) 27

Summary-2 • Although the extent of improvement at 1 year was similar with TAVR 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 28

Conclusions • Taken together with previous data, these findings demonstrate that for patients suitable 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 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 29