1-YEAR OUTCOMES FROM JOHN WEBB, MD

Transcription

1 1-YEAR OUTCOMES FROM JOHN WEBB, MD ON BEHALF OF THE SAPIEN 3 INVESTIGATORS UNIVERSITY OF BRITISH COLUMBIA VANCOUVER, CANADA

2 Potential conflicts of interest Speaker's name: John Webb I have the following potential conflicts of interest to report: Consultant to Edwards Lifesciences

3 Edwards SAPIEN 3 Transcatheter Heart Valve Bovine pericardial tissue Enhanced frame geometry for ultra-low delivery profile Outer skirt minimizes paravalvular leak

4 Delivery Systems Edwards Commander System Edwards Certitude System 14F esheath compatible Improved coaxial alignment Accurate positioning 18F Sheath compatible Ergonomic design SAPIEN 3 Valve Size 23 mm 26 mm 29 mm Edwards esheath 14F 14F 16F Minimum Vessel Diameter 5.5 mm 5.5 mm 6.0 mm SAPIEN 3 Valve Size 23 mm 26 mm 29 mm Certitude Sheath 18F 18F 21F 14F esheath compatible for 23 mm and 26 mm SAPIEN 3 valves. 16F esheath compatible for 29 mm SAPIEN 3 valve. 18F Certitude Sheath compatible for 23 mm and 26 mm SAPIEN 3 valves. 21F Certitude Sheath compatible for 29 mm SAPIEN 3 valve.

5 SAPIEN 3 CE Mark Trial Design Non-randomized, prospective, multicenter study assessing the safety and efficacy of the Edwards SAPIEN 3 Transcatheter Heart Valve (THV) in patients with symptomatic, severe aortic stenosis who are eligible for surgical AVR SAPIEN 3 CE High Risk*: STS Score 8 or EuroSCORE 15 Intermediate Risk : STS Score 4 or EuroSCORE Patients With Procedure TF = 96 TAA = Patients at 30 Days 99.3% Completed FU 127 Patients at 1 Year 100% Completed FU Primary Endpoint: All cause mortality at 30 days post-index procedure SAPIEN 3 CE IR (Extension) Intermediate Risk: STS Score 4 8 or LogEuroSCORE Patients With Procedure TF = 101 Patients at 30 Days Primary Endpoint: All cause mortality at 30 days post-index procedure Follow Up: 30 Days, 1 Year, Annually to 5 Years *France STS 10, EuroSCORE 20. Excluding France.

6 Enrollment Centers SITE PATIENTS Bad Nauheim, Germany Kerckhoff Clinic 22 Hamburg, Germany University Hospital 21 London, UK King's College Hospital 17 Vancouver, Canada St Paul's Hospital 14 Essen, Germany West German Heart Center 14 London, UK St Thomas Hospital 11 Massy, France Institut Hospitalier Jacques Cartier 9 Belfast, UK Royal Victoria Hospital 9 Karlsruhe, Germany Municipal Hospital 8 London, UK The Heart Hospital 7 Cologne, Germany University Hospital 6 Padova, Italy University Polyclinico 5 Paris, France CHU Bichat Claude-Bernard 2 Rouen, France CHU Charles Nicolle 2 Toulouse, France CHU Rangueil 2 Plymouth, UK Plymouth Hospital 1 Total Enrolled (N) patients from 16 centers in 5 countries Canada UK Germany France Italy

7 Baseline Patient Characteristics A v e r a g e S T S S c o r e = 7.4% A v e r a g e A g e = 83.6 yrs TF 64% TAA 36% Male 46% Female 54% 26.7% 53.3% 20.0% 23 mm 26 mm 29 mm

8 Baseline Characteristics Baseline Characteristics (%) TF PATIENTS (N = 96) TAA PATIENTS (N = 54) P-VALUE STS PROM Score 7.5 ± ± Logistic EuroSCORE (%) 19.8 ± ± Peripheral Vascular Disease Previous Myocardial Infarction Previous CABG Atrial Fibrillation Previous Aortic Valvuloplasty Previous Pacemaker Implantation Carotid Disease Porcelain Aorta Prior Stroke

9 Procedural Characteristics Variable TF PATIENTS (N = 96) Variable ALL PATIENTS (N = 150) Femoral Access/Anesthesia Procedural Outcomes General 63.5% Conscious Sedation 36.5% Femoral Access/Closure Percutaneous/Closure Device 95.8% Surgical 4.2% Technical Success* 93.3% Correct Placement at Intended Site 99.3% Post-dilation 3.3% Procedural Events Coronary Obstruction 0.0% Valve-in-Valve 0.0% Conversion to Conventional Surgery 0.7% ECMO Support 0.7% *No procedural mortality, correct positioning, and only one valve implanted.

10 Freedom From All-Cause Mortality TF- Population F R E E D O M F R O M A L L - C A U S E M O R T A L I T Y 100% 90% 80% 97.9% 91.6% 70% 60% 50% 40% 30% 20% 10% 0% Months Patients at Risk

11 1 Year KM Freedom from All-Cause Mortality TF Populations SOURCE SOURCE XT SAPIEN 3 100% 90% 80% 70% 91.6% 85.1% 80.1% 60% 50% 40% 30% 20% 10% Pts at Risk: 0% Months SOURCE SOURCE XT SAPIEN

12 Freedom From Cardiovascular Mortality TF Population 100% 90% 80% F R E E D O M F R O M C A R D I O V A S C U L A R M O R T A L I T Y 97.9% 97.9% 70% 60% 50% 40% 30% 20% 10% 0% Months Patients at Risk

13 Stroke Rate at 30 Days and 1 Year TF- Population (N = 96) 100% 3 0 D A Y 100% 1 Y E A R 90% 90% 80% 80% 70% 70% 60% 60% 50% 50% 40% 40% 30% 30% 20% 20% 10% 0% 1.1% 0.0% 10% 0% 2.1% 1.1% All-Stroke Disabling All-Stroke Disabling

14 Clinical Outcomes at 30 Days and 1 Year AT Population TF (N = 96) KM Event Rate (%) TAA (N = 54) KM Event Rate (%) Clinical Outcome 30 Days 1 Year 30 Days 1 Year All-Cause Mortality 2.1% 8.4% 11.1% 24.3% Cardiac Mortality 2.1% 2.1% 9.3% 13.3% All-Stroke 1.1% 2.1% 5.7% 8.3% Disabling Stroke 0% 1.1% 0% 0% Myocardial Infarction 2.1% 3.2% 0% 2.5% New-Onset Atrial Fibrillation New Permanent Pacemaker 7.3% 7.3% 20.7% 23% 14.6%* 15.7% 17.2% 19.8% Valve Thrombosis 0% 0% 0% 0% CHF/Worsening CHF 0% 0% 0% 0% SVD Requiring Repeat Procedure 0% 0% 0% 0% Valve Embolization 0% 0% 0% 0% *92% were implanted within 48 hours of index procedure.

15 Functional Improvement at 30 Days and 1 Year AT Population N Y H A C L A S S ( P A I R E D A N A L Y S I S ) I II III IV p < p > % 6.5% 0.8% 0.8% 4.0% 4.8% 80% 60% 77.4% 48.4% 56.5% 40% 20% 46.8% 37.9% 0% 16.1% Baseline 30 Days 1 Year N = 124 N = 124 N = 124 *p-values compare NYHA Classes I/II versus NYHA Classes III/IV between baseline and 30 days and between 30 days to 1 Year using McNemar s tests.

16 Gradient, mm Hg Echocardiographic Data VI Population M E A N G R A D I E N T & E F F E C T I V E O R I F I C E A R E A ( E O A ) P A I R E D A N A L Y S I S 80 Mean Gradient EOA p < p < EOA, cm p < p < Baseline 30 Days 1 Year No. of Patients EOA Mean Gradient

17 Paravalvular AR at 30 Days and 1 Year VI Population A L L P A T I E N T S P A I R E D A N A L Y S I S 100% None/Trace Mild Moderate Severe 3.4% 2.0% 100% None/Trace Mild Moderate Severe p < % 2.2% 80% 23.9% 14.0% 80% 24.7% 14.6% 60% 60% 40% 72.7% 84.0% 40% 70.8% 83.2% 20% 20% 0% 30 Days 1 Year N = 117 N = 100 0% 30 Days 1 Year N = 89 N = 89

18 Conclusions - The SAPIEN 3 Trial The one-year survival rate in the transfemoral cohort (91.6%) is the highest reported in a multi-center, prospective, fully CEC adjudicated TAVI study Low incidence of stroke at 1 year (2.1%) in the transfemoral cohort No valve thrombosis, structural valve deterioration, migration, or embolization The incidence of moderate paravalvular AR remained low at 1 year (2.1%), with no severe paravalvular AR

19 Implications - The SAPIEN 3 Trial The results of the SAPIEN 3 trial via the transfemoral approach Set a new standard of care for patients at high risk for surgical AVR Question whether TAVI should be the new standard of care in the elderly

20 30-DAY INTERMEDIATE RISK OUTCOMES FROM JOHN WEBB, MD ON BEHALF OF THE SAPIEN 3 INVESTIGATORS UNIVERSITY OF BRITISH COLUMBIA VANCOUVER, CANADA

21 Edwards Commander Delivery System Improved coaxial alignment Accurate positioning Distal flex Fine control of valve positioning SAPIEN 3 Valve Size 23 mm 26 mm 29 mm Edwards esheath 14F 14F 16F Minimum Access Vessel Diameter 5.5 mm 5.5 mm 6.0 mm

22 SAPIEN 3 CE Mark Trial Design Non-randomized, prospective, multicenter study assessing the safety and efficacy of the Edwards SAPIEN 3 Transcatheter Heart Valve (THV) in patients with symptomatic, severe aortic stenosis who are eligible for surgical AVR SAPIEN 3 CE High Risk*: STS Score > 8 or EuroSCORE > 15 Intermediate Risk**: STS Score > 4 or EuroSCORE > 10 SAPIEN 3 CE IR Intermediate Risk: STS Score > 4 to < 8 or Log EuroSCORE > 10 to < Patients With Procedure TF = 96 TAA = Patients at 30 Days 99.3% Completed FU 127 Patients at 1 Year 100% Completed FU Primary Endpoint: All cause mortality at 30 days post-index procedure 101 Patients with TF Procedure Patients at 30 Days 100% Completed FU Primary Endpoint: All cause mortality at 30 days post-index procedure Follow Up: 30 Days, 1 Year, Annually to 5 Years

23 SAPIEN 3 CE IR Baseline Patient Characteristics (1) Average Age = 84.4yrs Male 45.5% Female 54.5% N = 101 TF 100% 45.5% 31.7% 21.8% 23 mm 26 mm 29 mm

24 SAPIEN 3 CE IR Baseline Patient Characteristics (2) Variable N = 101 STS Score 5.2 ± 1.7 % Logistic EuroSCORE 13.2 ± 3.8 % NYHA Class III / IV 64.4% Peripheral Vascular Disease 15.8% Previous Myocardial Infarction 10.9% Previous CABG 10.9% Prior Stroke 8.9% Diabetes 26.7% Atrial Fibrillation 22.9% COPD 21.8% Previous Pacemaker Implantation 6.9% Porcelain Aorta 4.0% AV Effective Orifice Area (cm2) 0.7 ± 0.2 AV Mean Gradient (mm Hg) 47.2 ± 13.5 LV Ejection Fraction (LVEF) (%) 57.4 ± 11.6

25 SAPIEN 3 CE IR Procedural Characteristics Variable N = 101 Anesthesia / Access Conscious Sedation 54.5% Percutaneous/Closure Device 90.1% Procedural Outcomes Correct Placement at Intended Site 100% Post-dilation 4% Technical Success* 98% Procedural Events Conversion to Conventional Surgery 1% Valve-in-Valve 1% Coronary Obstruction 0% Valve Embolization 0% Annular Rupture 0% *No procedural mortality, correct positioning, and only one valve implanted.

26 SAPIEN 3 CE IR Clinical Outcomes at 30 Days 100% 80% 60% 40% Mortality N = 101 Stroke All-Cause Cardiovascular All-Stroke Disabling 100% 80% 60% 40% 20% 0% 1% 1% 20% 0% 4% 2%

27 Edwards SAPIEN Valves All-Cause Mortality at 30 Days AT Populations- KM Event Rates (%) 20% 15% 10% 5% 6.3% 5.2% 3.7% 4.5% 3.5% 2.1% 2.2% 1.6% 1.1% 1.1% 1.0% 0% P1B (TF) P1A (All) P1A (TF) P2B (TF) P2B XT (TF) S3 CE (TF) S3HR (All) S3HR (TF) S3i (All) S3i (TF) S3 CE IR (TF) SAPIEN SAPIEN XT SAPIEN 3 SAPIEN 3 IR

28 SAPIEN 3 CE IR Clinical Outcomes at 30 Days N=101 KM Event Rate (%) Clinical Outcome 30 Days Major Vascular Complications 2% Life-Threatening Bleeding 2% Myocardial Infarction 0% Acute Kidney Injury 2% New-Onset Atrial Fibrillation 6.9% New Permanent Pacemaker 4% Valve Thrombosis 0% CHF/ Worsening CHF 0% SVD Requiring Repeat Procedure 0% VI, valve implant = all enrolled patients who received a SAPIEN 3 implant, and retained the valve upon leaving the cath lab.

29 SAPIEN 3 CE IR Paravalvular AR at 30 Days 100% 2.3% 80% 26.4% 60% 40% 71.3% 20% 0% 30 Days None/Trace Mild Moderate Severe N = 87

30 SAPIEN 3 Studies US and CE Clinical Outcomes at 30 Days 100% 80% 60% 40% 20% 0% M O R T A L I T Y 2% 2.1% 1% 1% S3 US HR S3 CE HR S3i US IR S3 CE IR 100% 80% 60% 40% 20% 0% D I S A B L I N G S T R O K E 0.8% 1.1% 1.0% 2.0% S3 US HR S3 CE HR S3 US IR S3 CE IR M A J O R V A S C U L A R C O M P L I C AT I O N S 100% 80% 60% 40% 20% 5.3% 4.2% 5.9% 2.0% 0% S3 US HR S3 CE HR S3 US IR S3 CE IR 100% 80% 60% 40% 20% 0% M O D E R AT E /SEVERE PVL 3.8% 3.4% 2.3% S3i & HR US S3 CE S3 CE IR

31 Conclusions - The SAPIEN 3 Trial Intermediate-risk patients treated with the Edwards SAPIEN 3 valve had notably low mortality at 30 days. There were very low rates of all other major complications, notably major vascular complications and new permanent pacemaker implantation. There was excellent hemodynamic performance, with very low incidence of significant paravalvular regurgitation.

32 Implications - The SAPIEN 3 Trial These results represent at least parity with the best surgical outcomes. This suggests that SAPIEN 3 TAVR may be expected to challenge savr as the gold standard therapy in elderly patients with AS.