Slide 1: Primary Results From the Evolut Low Risk Trial
Primary Results From the Evolut Low Risk Trial Michael J. Reardon, MD, FACC Houston Methodist DeBakey Heart & Vascular Institute, Houston, TX For the Evolut Low Risk Trial Investigators
Slide 2: Disclosure Statement of Financial Interests
Disclosure Statement of Financial Interests Within the past 12 months, I have had a financial interest/arrangement or affiliation with the organization(s) listed below. Financial Relationship Company Consultant (fees paid to institution) Medtronic Medtronic personnel performed all statistical analys
Slide 3: Background
Background • We performed a series of randomized controlled trials in patients with severe aortic stenosis across a spectrum of surgical risk. • In high-risk patients, TAVR was superior to SAVR for the primary endpoint to 2 years1 and similar at 5 years.2 1Reardon et al. J Am Coll Cardiol 2015; 66:
Slide 4: Background: SURTAVI Trial Results
Background • The SURTAVI intermediate risk trial showed noninferiority at interim analysis. • The final analysis of the SURTAVI Trial confirmed the early Bayesian results, showing TAVR noninferior to SAVR. 30% Interim Analysis from the SURTAVI Trial1 30% Final Analysis from the SURTAVI Trial2 Death
Slide 5: Objective
Objective To assess the safety and efficacy of TAVR with the Evolut self- expanding supra-annular valve compared with surgical AVR in patients with a low predicted risk of 30-day surgical mortality.
Slide 6: Study Administration
Study Administration Principal Investigators: Jeffrey Popma, Michael Reardon Executive Committee: Jeffrey Popma, Michael Reardon, G. Michael Deeb, Steven Yakubov Steering Committee: David Adams, Stan Chetcuti, G. Michael Deeb, John Forrest, Thomas Gleason, John Heiser, William Mehri, Mubashir Mumtaz
Slide 7: Participating Sites in the United States
Participating Sites in the United States Swedish MC Univ. of Michigan St. John Hospital Oregon Health & Science Univ. Sanford MC Univ. Vermont MC Case MC Mass General Beth Israel Deaconess Baystate MC Abbott NW Yale New Haven Hospital Spectrum Health Strong Memorial North Shore Univ. Hospital Mercy
Slide 8: Australia, Canada, Europe, Japan and New Zealand
Australia, Canada, Europe, Japan and New Zealand CHRU de Lille Sapporo Higashi Taoushukai Hospital Jacques Cartier Sendai Kousei Hospital Sakakibara Heart Institute Shonan Kamakura Royal North Shore Clinique Kokura Memorial General Hospital St. Vincent’s Hospital Osaka Pasteur Hospital General Hospi
Slide 9: Study Design
Study Design Lor fk Low Surgical Risk HeartTeam Evaluation ese screening Committee Confirmed eligibility 1:1 Randomization Stratified by site and need for revascularization TAVR only TAVR + PCI SAVR only SAVR + CABG LTI Sub-Study LTI Sub-Study
Slide 10: Study Endpoints
Study Endpoints Primary Safety and Effectiveness Endpoint All-cause mortality or disabling stroke at 2 years Hierarchical Powered Secondary Endpoints Other Secondary Endpoints • 30-day safety composite of Noninferiority – All-cause mortality • Mean gradient at 1 year – Disabling stroke • EOA at 1 ye
Slide 11: Key Inclusion Criteria
Key Inclusion Criteria Symptomatic severe AS1: • Aortic valve area ≤1.0 cm² (or aortic valve area index <0.6 cm2/m2), OR mean gradient ≥40 mmHg OR Vmax ≥4 m/sec at rest Asymptomatic very severe AS1: • Aortic valve area ≤1.0 cm² (or aortic valve area index <0.6 cm2/m2), AND Vmax ≥5 m/sec or mean grad
Slide 12: Key Exclusion Criteria
Key Exclusion Criteria • Contraindication for placement of a bioprosthetic valve • Multivessel coronary artery disease with SYNTAX score >22 • Bicuspid aortic valve verified by imaging • Hypersensitivity or contraindication to all anticoagulation/ antiplatelet regimens • Any PCI or peripheral interv
Slide 13: Statistical Methods
Statistical Methods Noninferiority Testing of the Primary Endpoint • This was a randomized, multinational, noninferiority trial. Posterior Distribution of the Difference (TAVR rate – SAVR rate) • The Bayesian adaptive design prespecified an Noninferiority “early-win” interim analysis when 850 margin
Slide 14: Patient Flow
Patient Flow *Additional patients were randomized to permit completion of the LTI substudy and to enroll a Japanese cohort.
Slide 15: Study Timeline and Valves Studied
Study Timeline and Valves Studied 2016 2017 2018 First Patient Randomized *Last Patient Randomized Mar. 28, 2016 Nov. 27, 2018 CoreValve 31 mm Evolut R: 23, 26, 29 Added Evolut R 34 mm Evolut PRO: 23, 26, 29 mm Primary Endpoint Assessment Dec. 27, 2018 Vascular access 99% transfemoral 0.6% subcl
Slide 16: RESULTS
RESULTS
Slide 17: Baseline Characteristics
Baseline Characteristics Mean ± SD or % TAVR (N=725) SAVR (N=678) Age, years 74.1 ± 5.8 73.6 ± 5.9 Female sex 36.0 33.8 Body surface area, m2 2.0 ± 0.2 2.0 ± 0.2 STS PROM, % 1.9 ± 0.7 1.9 ± 0.7 NYHA Class III or IV 25.1 28.5 Hypertension 84.8 82.6 Chronic lung disease (COPD) 15.0 18.0 Cerebrovascula
Slide 18: Baseline Cardiac Risk Factors
Baseline Cardiac Risk Factors Mean ± SD or % TAVR (N=725) SAVR (N=678) SYNTAX Score 1.9 ± 3.7 2.1 ± 3.9 Permanent pacemaker, CRT or ICD 3.2 3.8 Prior CABG 2.5 2.1 Previous PCI 14.2 12.8 Previous myocardial infarction 6.6 4.9 Atrial fibrillation/flutter 15.4 14.5 Aortic valve gradient, mm Hg 47.0 ± 1
Slide 19: TAVR Procedural Data
TAVR Procedural Data % TAVR (N=724) General anesthesia 56.9 Iliofemoral access 99.0 Embolic protection device used 1.2 Pre-TAVR balloon dilation 34.9 Post-TAVR balloon dilation 31.3 More than 1 valve used 1.2 Partial or complete repositioning of the valve (Evolut/PRO only) 37.3 Staged or concomitant
Slide 20: Primary Endpoint
Primary Endpoint All-Cause Mortality or Disabling Stroke at 2 Years Primary Endpoint Met TAVR is noninferior to SAVR TAVR 5.3% SAVR 6.7% Posterior probability of noninferiority > 0.999 PP>0.999 -0.1 -0.05 0 0.05 0.1 0.15 TAVR –SAVR difference = -1.4% (95% BCI; -4.9, 2.1)
Slide 21: Hierarchical Secondary Endpoints
Hierarchical Secondary Endpoints All Noninferiority and Superiority Endpoints Met Difference Posterior TAVR SAVR TAVR–SAVR Probability Noninferiority (margin) (90% BCI) Mean gradient at 12 months (5 mmHg) 8.6 ± 3.7 11.2 ± 4.9 -2.6 (-3.1, -2.1) > 0.999 Mean EOA at 12 months (0.1 cm2) 2.3 ± 0.7 2.0 ±
Slide 22: Clinical Outcomes at 30 Days
Clinical Outcomes at 30 Days TAVR SAVR (95% BCI for Bayesian rates as % (N=725) (N=678) Difference) 30-Day composite safety endpoint* 5.3 10.7 (-8.3, -2.6) All-cause mortality 0.5 1.3 (-1.9, 0.2) Disabling stroke* 0.5 1.7 (-2.4, -0.2) Life-threatening or disabling bleeding* 2.4 7.5 (-7.5, -2.9) Acut
Slide 23: Clinical Outcomes at 1 Year
Clinical Outcomes at 1 Year TAVR SAVR (95% BCI for Bayesian rates as % (N=725) (N=678) Difference) All-cause mortality or disabling stroke 2.9 4.6 (-4.0, 0.4) All-cause mortality 2.4 3.0 (-2.6, 1.3) Cardiovascular mortality 1.7 2.6 (-2.7, 0.7) All stroke 4.1 4.3 (-2.4, 1.9) Disabling stroke* 0.8 2.4
Slide 24: K-M All-Cause Mortality or Disabling Stroke at 1 Year
K-M All-Cause Mortality or Disabling Stroke at 1 Year 10% TAVR Log-rank P = 0.065 Death or Disabling Stroke (%) SAVR 8% 1 Year 6% 4.6 2.7 30 Days 4% 2.5 0.7 2% 0% 0 1 2 3 4 5 6 7 8 9 10 11 12 No. at risk Months TAVR 725 718 648 435 SAVR 678 656 576 366 23
Slide 25: K-M Rates of All-Cause Mortality at 1 Year
K-M Rates of All-Cause Mortality at 1 Year 10% TAVR Log-rank P = 0.412 SAVR 8% All-Cause Mortality (%) 6% 1 Year 3.0 4% 30 Days 2.3 1.2 2% 0.4 0% 0 1 2 3 4 5 6 7 8 9 10 11 12 No. at risk Months Post Procedure TAVR 725 720 651 435 SAVR 678 665 583 373 24
Slide 26: K-M Disabling Stroke at 1 Year
K-M Disabling Stroke at 1 Year 6% Log-rank P = 0.024 Disabling Stroke (%) 4% 1 Year 2.3 0.7 2% 0% 0 1 2 3 4 5 6 7 8 9 10 11 12 No. at risk Months TAVR 725 720 648 435 SAVR 678 656 576 366
Slide 27: K-M Heart Failure Hospitalization at 1 Year
K-M Heart Failure Hospitalization at 1 Year 10% TAVR Log-rank P = 0.006 Heart Failure Hospitalization (%) SAVR 8% 1 Year 6.4 6% 4% 3.1 2% 0% 0 1 2 3 4 5 6 7 8 9 10 11 12 No. at risk Months TAVR 725 712 636 420 SAVR 678 649 561 358
Slide 28: Clinical Implications
Clinical Implications Death, Disabling Stroke and Heart Failure Hospitalizations to 1 Year 12% Composite Rates 10% TAVR SAVR Difference = –4.5% Estimated KM rates, % 8% 5.6% 10.2% P = 0.002 6.4% 6% HF Hospitalization 3.1% 2.3% 4% 0.7% Disabling Stroke 2% 2.3% 3.0% Death 0% TAVR SAVR
Slide 29: Procedural Time and Length of Stay
Procedural Time and Length of Stay Time in Cath Lab or OR Hospital Length of Stay 300 276.6± 79.5 7 6.2± 3.3 250 6 P<0.001 P<0.001 5 200 Minutes 148.2± 55.1 4 Days 150 3 2.6 ±2.1 100 2 50 1 0 0 TAVR SAVR TAVR SAVR
Slide 30: Valve Hemodynamics
Valve Hemodynamics 3.0 TAVR Statistically Superior At All Time Points 60.0 2.5 44.8 2.3 50.0 2.2 2.2 2.2 AV Mean Gradient, mm Hg Aortic Valve Area, cm2 2.0 40.0 44.2 2.0 2.0 2.0 2.0 1.5 30.0 1.0 0.9 20.0 11.2 11.2 12.3 0.8 10.5 0.5 10.0 8.4 8.7 8.6 9.0 0.0 0.0 Baseline 1 Mo 6 Mo 12 Mo 24 Mo Implante
Slide 31: Prosthesis-Patient Mismatch
Prosthesis-Patient Mismatch 30 25 P<0.001 P<0.001 20 8.2 4.4 15 1.1 10 1.8 15.5 15.7 5 9.9 5.0 0 TAVR SAVR TAVR SAVR NN=542 = 609 NN=463 = 541 N=341 N=293 1 Month 12 Months Moderate PPM Severe PPM Implant population. Core lab assessments.
Slide 32: Total Aortic Valve Regurgitation
Total Aortic Valve Regurgitation 3.5 0.5 4.3 1.5 Proportion of Patients with Echo (%) 100% 80% 60% 40% 20% 0% TAVR SAVR TAVR SAVR N=709 N=626 N=415 N=340 1 Month 1 Year None/Trace Mild Moderate Severe Implant population. Core lab assessments.
Slide 33: NYHA Functional Class
NYHA Functional Class 100 Proportion of Patients (%) 80 60 40 20 0 TAVR SAVR TAVR SAVR TAVR SAVR N=725 N=678 N=706 N=625 N=428 N=342 Baseline 1 Month 1 Year NYHA I NYHA II NYHA III NYHA IV
Slide 34: KCCQ Summary Score
KCCQ Summary Score KCCQ Overall Summary Score Patients Recover Quality of Life Sooner After TAVR 100 95 TAVR 90 SAVR 85 80 75 70 65 60 Baseline 30 Days 6 Months 12 Months Change from Baseline TAVR 20.0 ± 21.1 21.9 ± 21.2 22.2 ± 20.3 SAVR 9.1 ± 22.3 20.5 ± 20.5 20.9 ± 20.9 95% BCI for difference (8.6
Slide 35: Subgroup Analysis for Death or Disabling Stroke at 1 Year
Subgroup Analysis for Death or Disabling Stroke at 1 Year P for Subgroup TAVR SAVR Hazard Ratio (95% BCI) Interaction n/N (% KM rate at 1 Year) Age, years 0.50 < 75 10/351 (3.3) 14/350 (4.3) 0.70 (0.31-1.57) ≥ 75 7/374 (2.2) 13/328 (4.9) 0.45 (0.18-1.14) Sex 0.22 Male 10/464 (2.5) 21/449 (5.4) 0.44
Slide 36: Subgroup Analysis for Death or Disabling Stroke at 1 Year
Subgroup Analysis for Death or Disabling Stroke at 1 Year P for Subgroup TAVR SAVR Hazard Ratio (95% BCI) Interaction n/N (% KM rate at 1 Year) Peripheral Artery Disease 0.92 No 15/664 (2.7) 25/621 (4.6) 0.54 (0.29-1.03) Yes 1/54 (1.9) 2/56 (4.9) 0.46 (0.04-5.15) Diabetes Mellitus 0.81 No 12/497 (2.
Slide 37: Summary
Summary • TAVR with self-expanding supra-annular valves was noninferior to surgery for the primary endpoint of death or disabling stroke at 2 years in patients with severe aortic stenosis at low surgical risk. • At 30 days, TAVR showed a better safety and recovery profile than surgery, with less dea
Slide 38: Conclusion
Conclusion TAVR may be a preferred strategy to surgery in patients with severe aortic stenosis at low risk of surgical mortality.
Slide 39: NEJM: Transcatheter Aortic-Valve Replacement with a Self-Expanding Valve in Low-Risk Patients
The NEW ENGLAND JOURNAL of MEDICINE Transcatheter Aortic-Valve Replacement with a Self-Expanding Valve in Low-Risk Patients Jeffrey J. Popma, M.D., G. Michael Deeb, M.D., Steven J. Yakubov, M.D., Mubashir D., Hemal Gada, M.D., Daniel O'Hair, M.D. Tanvir Bajwa, M.D., John C. Heiser, William Merhi, D.
Slide 40: Thank you to the Evolut Low Risk patients, site personnel, investigators
Thank you to the Evolut Low Risk patients, site personnel, investigators and sponsor for making this and our series of randomized trials possible