Slide 1: SMART: Self-Expanding Versus Balloon-Expandable TAVR in Small Aortic Annuli
SMall Annuli Randomized to Evolut or SAPIEN SMART Self-Expanding Versus Balloon-Expandable TAVR in Patients with Aortic Stenosis and Small Aortic Annuli Primary Outcomes from the Randomized SMART Trial Howard C. Herrmann, MD | Roxana Mehran, MD | Didier Tchétché, MD on behalf of the SMART Trial Inve
Slide 2: Disclosure of relevant financial relationships
Disclosure of relevant financial relationships Within the past 12 months, I or my spouse/partner have had a financial interest/arrangement or affiliation with the organization(s) listed below: Financial Relationship Company Abbott Vascular, Boston Scientific, Edwards LifeSciences, Institutional gran
Slide 3: Background: The SMART Trial
Background In multiple studies, the supra-annular self-expanding Evolut™ valve has been shown to have superior hemodynamic properties compared with the intra- annular balloon-expandable SAPIEN™* platform.1 The SMART Trial • Hemodynamic valve performance is linked to long- was designed to compare the
Slide 4: Trial organization
Trial organization Executive Independent Independent Independent CEC committee steering committee physician case and DSMB • Howard Herrmann • Sabine Bleiziffer planning committee Core laboratories • Joshua Rovin • Michael Deeb (blinded to clinical outcomes) • Roxana Mehran • Linda Gillam • Kendra Gr
Slide 5: Global site participation: 83 sites in 13 countries
Global site participation 83 sites in 13 countries 1 FINLAND 5 CANADA 1 DENMARK 2 UNITED KINGDOM 8 GERMANY 2 NETHERLANDS 1 SWITZERLAND 53 UNITED STATES 3 FRANCE 3 ITALY 1 PORTUGAL 1 SPAIN 2 ISREAL 5 SMART Trial
Slide 6: Trial design
Trial design Prospective, randomized controlled, post-market trial conducted at 83 international sites All-comer trial with all surgical risk categories Co-Primary Endpoints including bicuspid patients at 1 year with planned 5-year follow-up Key eligibility • Symptomatic severe AS† Co-Primary Endpoi
Slide 7: Patient flow
Patient flow 737 Randomized ITT Evolut ITT SAPIEN N=366 N=371 10 Exited prior to procedure 11 Exited prior to procedure 1 Net loss to crossovers [+1 Net gain to crossovers] [2 Evolut to SAPIEN] [2 Evolut to SAPIEN] [1 SAPIEN to Evolut] [1 SAPIEN to Evolut] AT Evolut 716 AT SAPIEN N=355 As-Treated N=
Slide 8: Statistical methods
Statistical methods Co-primary endpoint #1 Powered for noninferiority, margin of 8% Clinical outcome composite through 12 months As-treated population (1st attempted device) • Mortality K-M estimate with risk difference (90% CI) • Disabling stroke through 12 months • Heart failure rehospitalization
Slide 9: Statistical methods
Statistical methods If both primary endpoints were Hypothesis-tested secondary endpoints met, hierarchical testing of secondary endpoints occurred in 1 Hemodynamic mean gradient at 12 months a prespecified order. 2 Effective orifice area at 12 months Powered for superiority 3 Hemodynamic SVD (mean g
Slide 10: Baseline characteristics
Baseline characteristics Characteristic Evolut (N=355) SAPIEN (N=361) Age – yr 80.1 ± 6.3 80.3 ± 6.1 Female sex 87.9% 85.6% STS-PROM score – % 3.3 ± 1.9 3.2 ± 1.7 NYHA functional class III/IV 43.3% 39.9% Diabetes 29.3% 34.1% Hypertension 82.5% 86.7% COPD or chronic lung disease 18.0% 17.6% Cerebrova
Slide 11: Valve and procedural data
Valve and procedural data Valve size Procedural characteristics and outcomes Evolut SAPIEN Evolut SAPIEN P Valuea Aortic annulus size Characteristic (N=355) (N=361) (N=355) (N=361) Mean area (mm2) 380.9 ± 34.2 382.8 ± 33.9 Total time in the 116 ± 44 106 ± 43 0.002 procedure roomb (min) Mean perimete
Slide 12: Co-primary endpoint 1: clinical outcome composite
Co-primary endpoint 1: Clinical outcome composite through 12 months powered for noninferiority Mortality, Disabling Stroke, or HF Rehospitalization 20% p<0.001 for noninferiority • Difference at 12 months, -1.2% (90% CI -4.9%, 2.5%) Evolut SAPIEN HR 12 Months • HR 0.90 (95% CI 0.56, 1.43) (N=355) (N
Slide 13: Co-primary endpoint 2: bioprosthetic valve dysfunction
Co-primary endpoint 2: BVD through 12 months powered for superiority Bioprosthetic Valve Dysfunction through 12 months Difference, -32.2% (95% CI -38.7%, -25.6%) Evolut SAPIEN P Value p<0.001 for superiority (N=350) (N=365) 50 41.6% BVD composite 9.4% 41.6% <0.001 40 HSVD 3.2% 32.2% 30 NSVD 5.9% 18.
Slide 14: Prespecified subgroup analyses for the co-primary endpoints
Prespecified subgroup analyses for the co-primary endpoints Clinical Outcome Composite Through 12 Months BVD Through 12 Months No significant interactions were observed between treatment and any of the prespecified baseline subgroups with respect to either of the co-primary endpoints. 14 SMART Trial
Slide 15: Hypothesis-tested secondary endpoints
Hypothesis-tested secondary endpoints Mean gradient† at 12 months, mmHg EOA† at 12 months, cm2 50 Difference, -7.9 (95% CI -8.8, -7.0) Difference, 0.48 (95% CI 0.40, 0.56) p<0.001 for superiority p<0.001 for superiority 40 3 30 Mean, 2 20 1.98 ± 0.47 Mean, Mean, Mean, 15.7 ± 6.7 1.50 ± 0.35 10 1 7.7
Slide 16: Additional safety outcomes
Additional safety outcomes 30 Days 12 Months Evolut SAPIEN Log-Rank Evolut SAPIEN Log-Rank KM% (N=355) (N=361) P Value (N=355) (N=361) P Value Pacemaker implanta 12.1% 7.8% 0.055 14.0% 9.3% 0.051 Pacemaker implant 11.1% 7.2% 0.067 12.8% 8.7% 0.063 Prosthetic valve endocarditis 0.0% 0.0% N/A 0.6% 2.3
Slide 17: Other hemodynamic outcomes at 12 months
Other hemodynamic outcomes at 12 months Doppler velocity index† Severe Prosthesis-Patient Total Aortic Regurgitation Difference, 0.19 (95% CI 0.17, 0.21) Mismatch (VARC-3) ≥Mild total AR at 12 months: p<0.001 14.1% Evolut vs 20.3% SAPIEN, p=0.043 Difference, -6.8% (95% CI -10.9, -2.7) Mean, p<0.001
Slide 18: Alternative bioprosthetic valve dysfunction definitions
Alternative bioprosthetic valve dysfunction definitions Evolut SAPIEN P Value Alternative definition Difference (N=350) (N=365) (Superiority) Evolut Better SAPIEN Better BVD composite ESC (Capodanno)1 11.5% 43.7% -32.2% <0.001 VARC-32 7.4% 22.4% -15.0% <0.001 SMART (primary endpoint 6.3% 28.3% -22.0
Slide 19: Quality of life
Quality of life Evolut demonstrated significantly better VARC-3 Ordinal Outcome for quality of life at 12 months KCCQ Overall Summary Score, Mean ± SD VARC-3 KCCQ ordinal outcome at 12 months Evolut vs SAPIEN, p=0.034 100 80.8 82.2 74.9% 67.8% Improvement Improvement Improvement at 12 months 80 100%
Slide 20: Summary
Summary The SMART trial is the largest, most rigorous trial to date, to randomize patients to the 2 most widely used TAVR devices, and the largest TAVR trial to enroll mostly women. Based on the large differences observed in The SMART trial met both primary and all 5 prespecified secondary endpoints
Slide 21: Thank You to All of Our Trial Investigators, Research Coordinators, and Top Enrolling Sites!
Thank You to All of Our Trial Investigators, Research Coordinators, and Top Enrolling Sites! • The Leeds Teaching Hospitals NHS Trust, Leeds, UK • Herz- und Diabeteszentrum NRW, Ruhr-Universität Bochum, Bad Oeynhausen, Germany • Allegheny General Hospital, Pittsburgh, PA • Lankenau Medical Center, W
Slide 22: Published today in the New England Journal of Medicine
Published today in the New England Journal of Medicine 22 SMART Trial
Slide 23: Backup
Backup 23 SMART Trial
Slide 24: Definitions
Definitions Severe prosthesis-patient mismatch per VARC-31: indexed effective orifice area of ≤0.65 cm2/m2 for body-mass index (BMI) <30 kg/m2 or ≤0.55 cm2/m2 for BMI ≥30 kg/m2. Bioprosthetic valve dysfunction per VARC-31: Based on a composite of (1) structural valve dysfunction, defined as mean gra
Slide 25: SMART Trial Clinical Sites
SMART Trial Clinical Sites • The Leeds Teaching Hospitals NHS, Leeds, UK • University of Florida, Gainesville, FL • Morristown Medical Center, Morristown, NJ • Allegheny General Hospital, Pittsburgh, PA • Toronto General Hospital, Toronto, Canada • Los Robles Hospital & Medical Center, Thousand Oaks
Slide 26: Summary of valve sizes and valves implanted
Summary of valve sizes and valves implanted Last implanted valve model Last implanted valve size 4.3% 0.6% 100 90.1 17.1% Medtronic 90 Evolut R 80 68.9 Evolut PRO 70 78.0% Evolut PRO+ 60 Evolut FX 50 40 28.9 19.2% 30 Edwards 20 SAPIEN 3 7.9 10 2.3 1.9 SAPIEN Ultra 0 23mmSEV26mm 29mm 20mm 23mmBEV26mm
Slide 27: Global site participation
Global site participation United States UPMC Presbyterian University Hospitals Cleveland Medical Center Cleveland Clinic CentraCare Heart & Vascular Center MN – Saint Cloud Hospital Ascension Saint John Hospital University University of Michigan Health of Pittsburgh Mayo Clinic System - University H
Slide 28: Global site participation
Global site participation Canada Denmark Finland France Centre Hospitalier Universitaire de Clermont-Ferrand - Gabriel-Montpied Vancouver Island Health Authority/Royal Jubilee Hospital Hôpital Haut-Lévêque – Rigshospitalet CHU de Bordeaux Montreal Heart Institute Saint Paul’s Hospital Clinique Paste