Current Evidence in TAVI patients using ACURATE and LOTUS valves

Transcription

1 Current Evidence in TAVI patients using ACURATE and LOTUS valves Giuseppe Tarantini, MD, PhD, FESC, Professor and Director of Interventional Cardiology University of Padua GISE President

2 Potential conflicts of interest Speaker's name : Giuseppe, Tarantini, Padua I have the following potential conflicts of interest to report: Receipt of honoraria or consultation fees: Abbott, Boston Scientific and Symetis, Edwards Lifesciences, Medtronic, Philips Healthcare, Sanofi Aventis, St. Jude Medical

3 Evidences

4 ACURATE neo TM TF Clinical Program TF20 FIM FIM Study High Risk Patients with Severe AS N=20; single arm; 4 centers - 3 valve sizes (21mm-27mm) 1⁰ Endpoint: All-cause mortality at 30d Complete TF89 SAVI-TF Registry PROGRESS PVL CE Mark Study High Risk Patients with Severe AS N=89; single arm; 6 centers - 3 valve sizes (21mm-27mm) 1⁰ Endpoint: Freedom from all-cause mortality at 30d Post-Market Registry High Risk Patients with Severe AS N=1000; single arm; 25 EU centers - 3 valve sizes (21mm-27mm) 1⁰ Endpoint: All-cause mortality at 30d 2⁰ Endpoints: Procedure success post-implant, device performance at 7d and 12m, VARC-2 safety and NYHA class at 30d and 12m Post-Market Registry N=500; single arm; prospective; 35 international sites Assessment of PVL at 7d, 30d, and 1y with CoreLab Complete PUBLISHED COMPLETED

5 Percent of Patients SAVI-TF Registry 30-Days and 12-Months Result Days 12 Months All Cause Mortality All Stroke New Pacemaker Implantation PVL 2 (Moderate) PVL > 2 (Mod/Severe) Mean Gradient (mmhg) EOA (cm 2 ) NYHA III/IV #PVL 2, PVL>2, Mean Gradient, and EOA were measured at 7 days/discharge and 1 year; 1-Year Endpoints are estimated Kaplan-Meier incidence 30-Day Endpoints and 7-Days PVL: Möllmann, et al. EuroIntervention 2018; 1-Year Endpoints and PVL: Kim, et al. JACC Cardiovasc Interv 2018

6 ACURATE neo Published Clinical Studies MORENA München, Regensburg, Bad Nauheim ACURATE neo vs SAPIEN 3 Observational, 1:2 propensity-matched multicenter ACURATE neo (n = 311) and SAPIEN 3 (n = 622) 3 high volume centers in Germany Device failure and early safety at 30 days 30 Days MULTICENTER COMPARISON IN PTS WITH SMALL ANNULI (A<400 mmq) ACURATE neo vs SAPIEN 3 Retrospective, 1:1 propensity-matched multicenter ACURATE neo (N = 92) and SAPIEN 3 (N = 92) 5 high volume centers in Germany, safety and performance of ACURATE neo and SAPIEN 3 in patients with small aortic annuli (Area <400 mmq) 30 Days & 1 Year SINGLECENTER COMPARISON AMONG 3 THVs ACURATE neo vs. CoreValve vs SAPIENT XT Prospective registry - the ACURATE neo (n=49), CoreValve (n=56), or SAPIEN XT (n=57) in a single center VARC-2 safety, device success, individual clinical endpoints, periprocedural outcomes, and echocardiography findings 30 Days

7 #1:MORENA RESULTS SUMMARY 30-days VARC-2 Safety and Performance Endpoints (% of pts) PM Rate and Hemodynamic Performance (% of pts/mmhg) [n.s.] [n.s.] [P = 0.024] ACURATE neo SAPIEN 3 [P = 0.008] [P = 0.021] 6.9 [P 0.001] [P 0.001] Early Safety Composite Endpoint (30 days) Device Failure Composite Endpoint 0 Permanent Pacemaker Implantation (in-hospital) PVL 2 (acute) Elevated Gradients Mean Gradient 20 mmhg (acute) (mmhg, discharge) Mean Gradient (mmhg, 30 days) Husser O. et al. JACC Cardiovasc Interv 2017;10:

8 #2: ACURATE neo vs. S3 in pts With Small Aortic Annulus Acute, 30-d, 1-y Outcome Summary (% of patients unless otherwise stated) Mauri V, et al. JACC Cardiovasc Interv 2017

9 #3: ACURATE neo Aortic Valve vs CV vs SAPIEN XT Clinical Outcomes at 30 days Mean age 83 years, 54% female, 75% NYHA Class III/IV; Few significant differences in baseline characteristics ACURATE neo (n=49) CoreValve (n=56) SAPIEN XT (n=57) VARC-2 Composite Early Safety 12% 25% 16% 0.21 All-cause Mortality 4% 11% 4% 0.22 Cardiovascular Death 4% 9% 2% 0.20 Stroke 0% 2% 2% 0.64 TIA 0% 5% 0% 0.06 Periprocedural MI 0% 4% 2% 0.40 AKI (Stage 2/3) 6% 7% 4% 0.69 Major vascular complication 2% 7% 5% 0.48 LT Bleeding 0% 4% 5% 0.29 Cardiac tamponade 0% 4% 2% 0.40 New PPMI 6% 25% 11% 0.01 Device Success 98% 86% 95% 0.04 P ACURATE neo compared favorably against CV and SXT CV was associated with lower device success due to higher valve embolization/ migration rates and higher PPMI Jatene, et al. Catheter Cardiovasc Interv 2017

10 ACURATE neo AS Study ACURATE neo2 Valve (n=120) Valve Hemodynamics* Paravalvular Regurgitation* Procedural success 97.5% Low rates of major vascular complications, life-threatening/disabling bleeding, and TAV-in-TAV deployment overall <5% 30-day safety outcomes were comparable to those observed in other TAVI studies in similar patient populations (Death + Disabling stroke <5%) * Core-lab adjudicated data. Values may not add to 100% due to rounding. As-treated population.

11 Learning Curve Effect - ACURATE neo Single Arm, Predictors of Procedural Outcome Study (N=500) First 100 cases Last 100 cases P-value Cover index, % Device landing zone calcium volume, mm Rapid pacing during deployment, % <0.001 Upper crown adjacent to leaflet, % All-cause 30-day mortality, % Device success (VARC 2) Paravalvular leak Kim WK, et al. JACC Cardiovasc Interv 2018

12 Evidences

13 Lotus Clinical Program REPRISE I REPRISE II/II EXT RESPOND RESPOND Extension REPRISE III REPRISE Japan Feasibility Study for Acute Safety in High Risk Patients N=11; single arm; 23mm valve size 1⁰ Endpoint: Device success (VARC) without MACCE CE Mark Study + Extended Cohort in High Risk Patients N=250; single arm; 23mm & 27mm valve sizes 1⁰ Endpoint: 30d Mortality Post Market Study, Safety & Performance in All Comers N=1014; single arm; 23mm, 25mm, 27mm valve sizes 1⁰ Endpoint: Mortality at 30d and 1yr Post Market Study, Safety & Performance in Lotus With Depth Guard N=50; single arm; 23mm & 25mm valve sizes 1⁰ Endpoint: Mortality at 30d and 1yr Pivotal Study for FDA Approval in High Risk & InOpPatients N=1014; RCT; Lotus vs CoreValve (52% CV Classic/R 48% Evolut R ) 1⁰ Endpoint: 30d Mortality, stroke, LT/major bleed, AKIN Stage 2/3 or major vascular complications Safety for PMDA Approval: Safety & Effectiveness, High Risk & InOp N=50; single-arm; 23, 25, & 27mm valve sizes 1 Endpoint similar to REPRISE III; safety at 30d, effectiveness at 6m 5-yr f/u TCT yr f/u PCR LV yr f/u PCR d Results PCR yr Results TCT 2018 Tokyo Valves 6-m Results 2018

14 REPRISE II 4Y Follow-Up N=250 (As treated) Paravalvular Aortic Regurgitation* NYHA Class* Mortality Disabling Stroke At 4 Y FU, the fully repositionable and retrievable Lotus Valve continues to demonstrate: Good hemodynamic results, Sustained functional improvement, No repeat procedures for valve dysfunction required and KM analyses * Core-lab adjudicated data. Values may not add to 100% due to rounding. As-treated population. Minimal paravalvular regurgitation

15 CoreValve better Lotus better Similar REPRISE III Key Results N=607 Lotus & N=305 CoreValve (Intent-to-Treat) Primary Safety* (Noninferiority; 30d) Primary Effectiveness (Superiority; 1y) Disabling Stroke (Superiority; 1y) LOTUS CV/ER P Value 20.3% (117/576) 17.2% (51/297) % (82/520) 26.0% (68/262) < % (21/587) 7.1% (21/297) 0.02 Moderate or greater PVL (Superiority; 1y) 0.9% (4/452) 6.9% (15/216) <0.001 Repeat Procedure (1y) 0.2% 2.0% TAV-in-TAV (1y) 0.0% 3.7% <0.001 Valve Malposition 0.0% 2.6% <0.001 Valve Thrombosis (1y) 1.5% 0.0% 0.03 Pacemaker (30d) [no prior PM] 35.5% 19.6% <0.001 Gradient/EOA (1y) 12.3mmHg/ 1.5cm 2 7.9mmHg/ 1.7cm 2 <0.001 * Composite of all-cause death, stroke, life-threatening/major bleed, major vcs & stage 2/3 AKI (Implanted) Composite of all-cause death, disabling stroke & moderate or greater PVL

16 Overall Stroke (%) REPRISE III Disabling Stroke at 1 Year 15 CoreValve Lotus HR 0.53 [0.29, 0.96] P= year results - TCT % 4.0% No. at risk CoreValve Lotus Days Feldman T, et al. JAMA 2018;319:27-37

17 LOTUS Edge (1Y) Combined Cohort N=36 (As treated) Valve Hemodynamics Paravalvular Regurgitation* Low rates of death and stroke (~5%) Sustained haemodynamics and functional improvement 97.1% none/trace paravalvular leak 15.2% rate of new permanent pacemaker vs ~30% with first-generation Lotus Limitation: small feasibility study; results need to be confirmed in REPRISE IV trial * Among patients with evaluable echocardiograms. As assessed by an independent core laboratory.

18 New Permanent Pacemaker to 30 Days TAVI Clinical Studies Trial (N) % Patients CoreValve Ext. Risk (N=489) CoreValve High Risk (N=390) EVOLUT R (N=241) REPRISE III (N=303) REPRISE III (N=601) REPRISE II/III EXT (N=250) RESPOND Ext (N=50) RESPOND (N=1014) PARTNER Inoperable (N=179) PARTNER High Risk (N=348) MORENA (N=622) MORENA (N=311) Bagur et al. (N=19) Jatene et al. (N=49) ACURATE neo TF89 (N=78) SAVI TF (N=998) Toggweiler et al. (N=175) Jatene et al. (N=56) Jatene et al. (N=57) PARTNER 2A (N=1011) PARTNER 2S3i (N=955) SURTAVI (N=864) High/ Extreme Risk Intermediate Risk CoreValve Evolut R Lotus, Lotus w/depth Guard Sapien Sapien XT Sapien S3 ACURATE neo Aortic Valve

19 New Permanent Pacemaker to 30 Days TAVI Clinical Studies Trial (N) CoreValve Ext. Risk (N=489) CoreValve High Risk (N=390) EVOLUT R (N=241) REPRISE III (N=303) REPRISE III (N=601) REPRISE II/III EXT (250) RESPOND Ext (N=50) RESPOND (N=1014) PARTNER Inoperable (N=179) PARTNER High Risk (N=348) MORENA (N=622) MORENA (N=311) Bagur et al. (N=19) Jatene et al. (N=49) ACURATE neo TF89 (N=78) SAVI TF (N=998) Toggweiler et al. (N=175) Jatene et al. (N=56) Jatene et al. (N=57) PARTNER 2A (N=1011) PARTNER 2S3i (N=955) SURTAVI (N=864) % Patients CoreValve 29.1 Evolut R Lotus, Lotus w/depth Guard High/ 16.4 Extreme Risk Sapien Sapien XT Sapien S ACURATE neo Aortic Valve ,1% ,5% 12,7% Intermediate 10.2 Risk

20 All Stroke to 1 Year TAVI Clinical Studies Trial (N) % Patients CoreValve CoreValve Ext. Risk (N=489) CoreValve High Risk (N=390) Evolut R EVOLUT R (N=241) 7.7 Lotus, Lotus w/depth Guard REPRISE III (N=297) REPRISE III (N=587) REPRISE II/III EXT (N=250) High/ Extreme Risk Sapien Sapien XT RESPOND (N=988) PARTNER Inoperable (N=179) Sapien S3 PARTNER High Risk (N=348) ACURATE neo TF89 (N=89) ACURATE neo Aortic Valve SAVI TF (N=1000) PARTNER 2A (N=1011) Intermediate Risk PARTNER 2S3i (N=930) 4.6 SURTAVI (N=879)

21 All Stroke to 1 Year TAVI Clinical Studies Trial (N) % Patients CoreValve CoreValve Ext. Risk (N=489) CoreValve High Risk (N=390) EVOLUT R (N=241) REPRISE III (N=297) REPRISE III (N=587) REPRISE II/III EXT (250) RESPOND (N=988) PARTNER Inoperable (N=179) PARTNER High Risk (N=348) ACURATE neo TF89 (N=89) SAVI TF (N=1000) 3.5 Intermediate PARTNER 2A (N=1011) 8.0 Risk 5,1% 6,8% 7% PARTNER 2S3i (N=930) 4.6 SURTAVI (N=879) High/ Extreme Risk Evolut R Lotus, Lotus w/depth Guard Sapien Sapien XT Sapien S3 ACURATE neo Aortic Valve

22 Trial (N) Moderate/Severe PVL to 1 Year TAVI Clinical Studies % Patients Valve CoreValve CoreValve Ext. Risk (N=327) 4.2 Evolut R CoreValve High Risk (N=390) EVOLUT R (N=188) REPRISE III (N=216) High/ Extreme Risk Lotus, Lotus w/depth Guard Sapien REPRISE III (N=452) REPRISE II/III EXT (N=250) Sapien XT RESPOND (N=545) PARTNER Inoperable (N=179) PARTNER High Risk (N=348) Sapien S3 ACURATE neo Aortic Valve ACURATE neo TF89 (N=66) 4.5 SAVI TF (N=587) PARTNER 2A (N=751) PARTNER 2S3i (N=900) Intermediate Risk SURTAVI (N=599)

23 Trial (N) Moderate/Severe PVL to 1 Year TAVI Clinical Studies % Patients Valve CoreValve CoreValve Ext. Risk (N=327) CoreValve High Risk (N=390) EVOLUT R (N=188) REPRISE III (N=216) REPRISE III (N=452) REPRISE II/III EXT (250) RESPOND (N=545) PARTNER Inoperable (N=179) PARTNER High Risk (N=348) ACURATE neo TF89 (N=66) SAVI TF (N=587) 3.6 Intermediate PARTNER 2A (N=751) 3.4 Risk 4% 0,4% 5% PARTNER 2S3i (N=900) 1.5 SURTAVI (N=599) High/ Extreme Risk Evolut R Lotus, Lotus w/depth Guard Sapien Sapien XT Sapien S3 ACURATE neo Aortic Valve

24 New Performance benchmarks For low-risk patients days) All-cause mortality 1% Major (disabling) strokes 1% Major vascular complications <3% New permanent pacemaker <10% Moderate-severe PVL <3% Martin Leon, TCT 2016

25 New Performance benchmarks For low-risk patients days) All-cause mortality 1% Major (disabling) strokes 1% Major vascular complications <3% New permanent pacemaker <10% Moderate-severe PVL <3% Martin Leon, TCT 2016