Five-Year Outcomes of Transcatheter Aortic Valve Replacement (TAVR) in Inoperable Patients With Severe Aortic Stenosis: The PARTNER Trial

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1 Five-Year Outcomes of Transcatheter Aortic Valve Replacement (TAVR) in Inoperable Patients With Severe Aortic Stenosis: The PARTNER Trial Samir R. Kapadia, MD On behalf of The PARTNER Trial Investigators TCT 2014 September 13, 2014

2 Background Transcatheter aortic valve replacement (TAVR) is the recommended treatment for inoperable patients with severe aortic stenosis (AS). Long term clinical benefit and valve performance in this population remain unknown.

3 PARTNER Study Design Symptomatic Severe Aortic Stenosis Inoperable N = 358 Severe Symptomatic AS with AVA< 0.8 cm 2 (EOA index < 0.5 cm 2 /m 2 ), and mean gradient > 40 mmhg or jet velocity > 4.0 m/s ASSESSMENT: Transfemoral Access 1:1 Randomization Inoperable defined as risk of death or serious irreversible morbidity of AVR as assessed by cardiologist and two surgeons exceeding 50%. TF TAVR n = 179 VS Standard Therapy n = 179 Primary Endpoint: All-Cause Mortality Over Length of Trial (Superiority) Primary endpoint evaluated when all patients reached one year follow-up. After primary endpoint analysis reached, patients were allowed to cross-over to TAVR.

4 Key End-Points for 5 Year Analysis All-Cause Mortality Cardiac Mortality Re-hospitalization Stroke NYHA functional class Echo-derived valve areas, transvalvular gradients, and paravalvular leak. Mortality outcomes stratified by STS score, paravalvular leak and age.

5 Study Flow Inoperable Cohort N = 358 Randomized Inoperable N = 179 Standard Therapy 85 / 85 patients 100% followed at 1 Yr 19 / 19 patients 100% followed at 3 Yrs 6 / 6 patients 100% followed at 5 Yrs* 10 Patients Withdrew Cross Over 11 pts Cross Over 9 pts N = 179 TAVR 124 / 124 patients 100% followed at 1 Yr 81 / 83 patients 97.6% followed at 3 Yrs 50 / 51 patients 98.0% followed at 5 Yrs* * ± 2 months follow-up window

6 Patient Characteristics Characteristic TAVR N = 179 Standard Rx N = 179 p-value Age yr 83.1 ± ± Male sex (%) STS Score 11.2 ± ± NYHA I or II (%) III or IV (%) CAD (%) COPD Any (%) O 2 dependent (%) Creatinine > 2 mg/dl (%) Frailty (%) Porcelain aorta (%) Chest wall radiation (%)

7 All-Cause Mortality (ITT) Crossover Patients Censored at Crossover Standard Rx (n = 179) TAVR (n = 179) 80.9% 87.5% 93.6% All-Cause Mortality (%) 50.8% 30.7% 68.0% 43.0% 53.9% 64.1% HR [95% CI] = 0.50 [0.39, 0.65] p (log rank) < % Months * In an age and gender matched US population without comorbidities, the mortality at 5 years is 40.5%.

8 Median Survival 11.1 Months p (log rank) < Months Months

9 All-Cause Mortality (ITT) Landmark Analysis HR [95% CI] = 0.50 [0.39, 0.65] p (log rank) < HR [95% CI] = 0.46 [0.32, 0.66] p (log rank) < Standard Rx (n = 179) TAVR (n = 179) HR [95% CI] = 0.47 [0.24, 0.94] p (log rank) = All-Cause Mortality (%) 0-1 Year 1-3 Years 61.1% 3-5 Years 50.8% 30.7% 33.4% 66.7% 38.9% Months

10 Cardiovascular Mortality (ITT) Crossover Patients Censored at Crossover Standard Rx (n = 179) TAVR (n = 179) Cardiovascular Mortality (%) 44.6% 20.5% 62.4% 30.7% 74.5% 41.2% 80.6% 47.6% HR [95% CI] = 0.41 [0.31, 0.55] p (log rank) < % 57.3% Months

11 Causes of Death 18% vs 34% Percent Patients 48% vs 33% n=179 n=179

12 All-Cause Mortality Stratified by STS Score (ITT) STS < 5 STS 5-15 STS > 15 p (log rank) = p (log rank) = p (log rank) = % 93.4% 93.3% 75.2% 73.7% Mortality (%) 55.9% Months Months Months Standard Rx (n = 12) Standard Rx (n = 123) Standard Rx (n = 43) TAVR (n = 28) TAVR (n = 113) TAVR (n = 38)

13 Cardiovascular Mortality Stratified by STS Score (ITT) STS < 5 STS 5-15 STS > 15 p (log rank) < p (log rank) < p (log rank) = % 91.8% 82.4% Mortality (%) 41.1% 61.6% 57.8% Months Months Months Standard Rx (n = 12) Standard Rx (n = 123) Standard Rx (n = 43) TAVR (n = 28) TAVR (n = 113) TAVR (n = 38)

14 Repeat Hospitalization (ITT) Standard Rx (n = 179) TAVR (n = 179) 83.0% 87.3% 72.5% 75.7% Rehospitalization (%) 53.9% 34.9% 43.1% 46.3% 47.6% 27.0% HR [95% CI] = 0.40 [0.29, 0.55] p (log rank) < Months

15 NYHA Class Over Time (ITT) Survivors p = NS p < p = NS p = NS 23.7% 30.0% 14.3% 40.0% 60.8% 50.0% 92.2% 93.9% N = Baseline 1 Year 3 Years 5 Years

16 Competing Risks Analysis (ITT) Death and Stroke Incidence (%) 14.6% 5.7% Months

17 Paravalvular Leak (AT) Percent of Evaluable Echocardiograms N =

18 Mortality by Paravalvular Leak All-Cause Mortality None-Mild (n = 142) Moderate-Severe (n = 23) Cardiovascular Mortality None-Mild (n = 142) Moderate-Severe (n = 23) 78.3% 74.6% 69.2% 51.3% p (log rank) = p (log rank) = 0.043

19 Mean Gradient & Valve Area (AT) EOA Mean Gradient Error bars = ± 1 Std Dev Mean Gradient (mmhg) Valve Area (cm²) N =

20 Mean Gradient & Valve Area (AT) Restricted to Patients with 5 Year Data EOA Mean Gradient Error bars = ± 1 Std Dev Mean Gradient (mmhg) Valve Area (cm²) N =

21 Subgroup Analysis All-Cause Mortality Hazard Ratio [95% CI] Overall (N=358) 0.50 [ ] Age < 85 (N=186) 0.46 [ ] Age 85 (N=172) 0.56 [ ] Male (N=166) 0.46 [ ] Female (N=192) 0.55 [ ] BMI 25 (N=170) 0.58 [ ] BMI > 25 (N=188) 0.44 [ ] STS 11 (N=170) 0.52 [ ] STS > 11 (N=187) 0.53 [ ] EF 55 (N=173) 0.47 [ ] EF > 55 (N=171) 0.61 [ ] Pulmonary Hypertension No (N=136) 0.56 [ ] Yes (N=103) 0.51 [ ] Mod / Sev MR No (N=261) 0.58 [ ] Yes (N=77) 0.30 [ ] Oxygen Dependent COPD No (N=270) 0.46 [ ] Yes (N=88) 0.68 [ ] Prior CABG or PCI No (N=182) 0.55 [ ] Yes (N=176) 0.46 [ ] Interaction p-value

22 TAVR Mortality Stratified by Age (ITT) 96.0% 91.8% 73.5% 70.4% Mortality (%) Months

23 Clinical Observations Mortality benefit was similar in elderly (>85 yr) patients compared to those 85 years. Cardiovascular mortality and all-cause mortality benefit was seen even in patients with high STS score. Patients with O2 dependent COPD may have less mortality benefit. Beyond early procedural risk of stroke there was no persistent risk over 5-year follow up. Moderate and severe paravalvular leak is associated with higher cardiovascular mortality particularly in patients with less comorbidities.

24 Main Conclusions At 5 years follow-up benefits of TAVR were sustained as measured by: All-Cause Mortality Cardiovascular Mortality Repeat Hospitalization Functional Status Valve durability was demonstrated with no increase in transvalvular gradient or attrition of valve area.

25 Thank You to the Dedicated Study Teams at All PARTNER Investigational Sites