Health Status Benefits of Transcatheter vs. Surgical Aortic Valve - PowerPoint PPT Presentation

Health Status Benefits of Transcatheter vs. Surgical Aortic Valve Replacement in Patients with Severe Aortic Stenosis at Intermediate Surgical Risk Results From The PARTNER 2 Trial David J. Cohen, M.D., M.Sc. On behalf of the PARTNER 2 Investigators Saint Luke’s Mid -America Heart Institute University of Missouri-Kansas City Kansas City, Missouri TCT 2016 | Washington, DC | November 1, 2016

Disclosure The PARTNER 2 Trial was funded by a research grant from Edwards Lifesciences, Inc.

Background • Improved quality of life (QOL) is a key goal of treatment for patients with severe AS and may be even more important than improved survival for many elderly patients • Prior studies have shown that transcatheter aortic valve replacement (TAVR) results in substantial and durable QOL benefits in extreme risk/inoperable patients and an early QOL benefit compared with surgical aortic valve replacement (SAVR) in patients at high surgical risk • However, the early QOL benefit of TAVR was confined to patients who were suitable for transfemoral access and was not seen in patients treated via the transapical approach

Background- 2 • In the PARTNER 2A trial, TAVR was found to be non- inferior to SAVR for the primary endpoint of 2-year death or disabling stroke among patients at intermediate surgical risk • There were differences in procedure-related complications and valve performance at 1 year, however, with some endpoints favoring TAVR and others favoring surgical AVR • The overall impact of these alternative treatments on health- related QOL from the patient’s perspective has not yet been reported

Study Objectives 1. To compare health-related quality of life outcomes among patients with severe AS and intermediate surgical risk treated with either TAVR or SAVR 2. To determine whether the QOL benefits of TAVR vs. SAVR vary over time 3. To examine whether the QOL benefits of TAVR vs. SAVR in the intermediate risk population differ according to access site or other patient characteristics

The PARTNER 2A Trial QOL Study Design Symptomatic Severe Aortic Stenosis at Intermediate Surgical Risk (>4%) based on Heart Team Assessment ASSESSMENT: Yes No Transfemoral Access Transfemoral (TF) Transapical (TA) / TransAortic (TAo) 1:1 Randomization (n=1550) 1:1 Randomization (n=482) TF TAVR Surgical AVR TA/TAo TAVR Surgical AVR VS. VS. (n=775) (n=775) (n=236) (n=246) QOL assessed from all patients using validated questionnaires at baseline, 1 month, 1 year, and 2 years

Methods: Quality of Life Instrument Description/Role • Heart Failure-specific QOL Kansas City Cardiomyopathy • Domains: Symptoms, Physical Questionnaire (KCCQ) Limitations, Quality of Life, Social Limitations • Scores: 0-100 (higher = better) • General physical and mental health SF-36 • Scores standardized such that mean=50, standard deviation=10 (higher = better) • Generic instrument for assessment of EQ-5D (EuroQOL) utilities and QALYs • Scores: 0-1 (0=death; 1=perfect health)

̶ Statistical Methods • Study Population: All patients with baseline QOL data (n=1833, 90.2%)  analyzed by ITT • Primary QOL Endpoint = KCCQ Overall Summary Score All other QOL scales considered secondary endpoints • Scores between groups compared using analysis of covariance (ANCOVA), adjusting for baseline health status and access site • Analytic plan specified that separate analyses would be performed for the transfemoral (TF) and transthoracic (TT) groups in case of a significant interaction between treatment effect and access site

Baseline Characteristics TAVR AVR (n = 950) (n = 883) 81  7 81  7 Age (yrs) Male gender 54.4% 55.4% 5.8  2.1 5.8  1.8 STS risk score Prior MI 18.1% 17.9% Prior CABG 23.7% 25.6% Prior Stroke 10.2% 10.2% COPD (O 2 dependent) 11.2% 9.7% 45  13 45  12 Mean AVG (mmHg) P = NS for all comparisons

Baseline Characteristics- QOL TAVR AVR (n = 950) (n = 883) 53.2  21.8 52.9  21.3 KCCQ Overall Summary 75-100 (~NYHA I) 18.4% 16.9% 60-74 (~NYHA II) 21.4% 22.9% 45-59 (~NYHA III) 23.5% 23.1% 0-45 (~NYHA IV) 36.7% 37.0% 36.1  8.9 35.9  8.7 SF-12 Physical 48.7  11.3 47.7  11.7 SF-12 Mental P = NS for all comparisons

Primary Endpoint KCCQ Overall Summary 90 MCID = 5 points TAVR SAVR 70 2 year D = 19 points 50 D = -0.4 D = 0.5 D = 11.4 P = NS P = NS P < 0.001 Significant interaction (P<0.001) between 30 treatment effect and access site for the -4 0 4 8 12 16 20 24 28 primary endpoint and multiple ANCOVA analysis; adjusted for baseline secondary endpoints MCID = minimum clinically important difference

KCCQ Overall Summary (Primary Endpoint) TF Subgroup 20 15 Treatment Difference (TAVR - AVR) 10 5 0 -5 -10 D = 9.9 D = -0.5 D = -1.2 D = 14.1 D = -0.1 D = 1.0 P<0.001 P=NS P=NS P<0.001 P=NS P=NS -15 -20 1 month 12 months 24 months P-values are for mean treatment effect of TAVR vs. SAVR

KCCQ Overall Summary (Primary Endpoint) TT Subgroup 20 15 Treatment Difference (TAVR -AVR) 10 5 0 -5 -10 D = 3.5 D = 3.5 D = -0.5 D = -0.5 D = -1.2 D = -1.2 P=NS P=NS P=NS P=NS P=NS P=NS -15 -20 1 month 12 months 24 months P-values are for mean treatment effect of TAVR vs. SAVR

Generic QOL and Utilities TF Subgroup SF-36 Mental SF-36 Physical 10.0 10.0 7.5 7.5 Treatment Difference (TAVR - AVR) Treatment Difference (TAVR - AVR) 5.0 5.0 2.5 2.5 0.0 0.0 -2.5 -2.5 -5.0 -5.0 D = 4.6 D = 0.1 D = 5.4 D = -0.8 D = 5.5 D = 1.2 D =0.6 D = -0.1 D = 0.4 P <0.001 P = NS P < 0.001 P = NS -7.5 P <0.001 P = NS P = NS P = NS -7.5 P = NS -10.0 -10.0 1 month 12 months 24 months 1 month 12 months 24 months EQ-5D Utilities 0.20 0.15 Treatment Difference (TAVR - AVR) 0.10 0.05 0.00 -0.05 -0.10 D = 0.066 D = -0.011 D = -0.002 P-values are for mean -0.15 P <0.001 P = NS P = NS treatment effect of TAVR vs. SAVR -0.20 1 month 12 months 24 months

Generic QOL and Utilities TT Subgroup SF-36 Mental SF-36 Physical 10.0 10.0 7.5 7.5 Treatment Difference (TAVR -AVR) Treatment Difference (TAVR -AVR) 5.0 5.0 2.5 2.5 0.0 0.0 -2.5 -2.5 D = 0.6 D = -0.1 D = 0.3 D = -0.1 D = 0.0 D = -.04 -5.0 -5.0 P = NS P = NS P = NS P = NS P = NS P = NS -7.5 -7.5 -10.0 -10.0 1 month 12 months 24 months 1 month 12 months 24 months EQ-5D Utilities 0.20 0.15 Treatment Difference (TAVR -AVR) 0.10 0.05 0.00 -0.05 D =0.007 D = 0.000 D = 0.018 -0.10 P = NS P = NS P = NS P-values are for mean -0.15 treatment effect of -0.20 TAVR vs. SAVR 1 month 12 months 24 months

KCCQ-Summary: Moderate or Substantial Improvement*: TF Subgroup * Improvement ≥ 10 points vs. baseline among patients with available QOL data

KCCQ-Summary: Moderate or Substantial Improvement*: TT Subgroup * Improvement ≥ 10 points vs. baseline among patients with available QOL data

Overall Clinical Status TF Cohort *P-values from ordinal logistic regression

Overall Clinical Status TT Cohort *P-values from ordinal logistic regression

TT vs. TF: Indirect Comparison KCCQ Summary Scale Non-randomized comparison

Summary-1 • Among patients with severe AS who were at intermediate risk for surgical valve replacement, both surgical and transcatheter AVR resulted in substantial improvement in disease-specific and generic HRQOL over 2 year follow-up – KCCQ Summary Scale ~ 20 points (MCID = 5) – SF-36 Physical ~ 4 points (MCID = 2) – SF-36 Mental ~ 3 points (MCID = 2) • Although the extent of improvement at 2 years was similar with TAVR and SAVR, there were important differences in the rate and extent of recovery at the earlier time points

Summary-2 • For patients eligible for a TF approach, TAVR resulted in substantial QOL benefits compared with SAVR at 1 month with similar QOL at later time points • For patients eligible only for a transthoracic approach (i.e., transapical or transaortic), there was no benefit of TAVR over SAVR at any time point • When both mortality and the extent of quality of life improvement were evaluated together, TF-TAVR was superior to SAVR at all follow-up timepoints

Conclusions • Taken together with previous data, these findings demonstrate that for intermediate risk patients suitable for a TF approach, TAVR provides both early and late benefits compared with surgical AVR from the patient’s perspective • The lack of benefit among patients ineligible for the TF approach suggests that a TT approach may not be preferable to SAVR in such patients – at least in the short to intermediate term • Further studies will be necessary to determine whether use of other alternative access sites (e.g., subclavian, carotid, transcaval) can overcome these limitations of the TT approach

Thank You MAHI Health Economics and Technology Assessment • Suzanne J. Baron, MD, MSc Elizabeth A. Magnuson, Sc.D. • Kaijun Wang, Ph.D. Suzanne Arnold, MD, MHA • Khaja Chinnakondepalli, MS PARTNER Investigators and Publications Office • Maria Alu, MS