Slide 1: One-year Outcomes of ACURATE neo2 vs Approved TAVR Devices: ACURATE IDE Trial
One-year Outcomes of ACURATE neo2 vs Approved TAVR Devices in All-risk Patients with Severe AS: the ACURATE IDE Trial Michael Reardon, MD Houston Methodist DeBakey Heart & Vascular Center Houston, TX On behalf of the ACURATE IDE Investigators
Slide 2: Disclosure of Relevant Financial Relationships
Disclosure of Relevant Financial Relationships Within the prior 24 months, I have had a relevant financial relationship with a company producing, marketing, selling, re-selling, or distributing healthcare products used by or on patients: Nature of Financial Relationship Ineligible Company Consultant
Slide 3: Background Clinical Experience
Background Clinical Experience ACURATE neo2 Aortic Valve System is commercially available in 60+ countries (outside US) with 80,000+ patients treated with the ACURATE Platform globally Post-market ACURATE neo2 PMCF Early neo2 Registry 3 PROVE Registry4 study/registry : N=250 N=554 N=1044 30 days1 1
Slide 4: ACURATE neo2 Valve Design
ACURATE neo2 Valve Design Unique frame design Self-expanding • Self-expanding Nitinol frame with top-down deployment open-cell frame • Open-cell design with axial stabilization arches • Supports unrestricted coronary access1 & predictable Porcine commissure alignment2 pericardium leaflets Supra-annu
Slide 5: ACURATE IDE Trial Design
ACURATE IDE Trial Design Prospective, multicenter, randomized study N=1500 patients with symptomatic severe native aortic stenosis indicated for TAVR Operators pre-specify valve type to be used if randomized to Control 1:1 Randomization CoreValve Evolut R Evolut Evolut PRO Evolut PRO+ N=244 ACURATE
Slide 6: ACURATE IDE Trial Administration
ACURATE IDE Trial Administration Principal Investigators Top Enrolling Sites Michael Reardon, MD Raj Makkar, MD Enrollment rank Investigator(s) Clinical Site Core Laboratories 1 Raj R Makkar Cedars-Sinai Medical Center Baim Institute for Clinical Research Eric Gnall Angiography & CT: 2 Lankenau Medi
Slide 7: Key Inclusion Criteria
Key Inclusion Criteria Severe Symptomatic Aortic Stenosis • AVA ≤ 1.0 cm2 or AVA index ≤ 0.6 cm2/m2 • AND mean gradient ≥ 40 mmHg or max AV velocity ≥ 4.0 m/s or Doppler velocity index ≤0.25 • NYHA Functional Class ≥ II • Heart Team agreement that subject is indicated for TAVR Documented aortic annu
Slide 8: Key Exclusion Criteria
Key Exclusion Criteria Anatomic Clinical • Unicuspid or bicuspid valve • Acute MI within 1 month • Pre-existing prosthetic aortic or mitral valve • Stroke or TIA within 6 months • Severe (4+) aortic, tricuspid, or mitral • Renal insufficiency (eGFR < 20 ml/min) and/or regurgitation renal replacement
Slide 9: Statistical Methods
Statistical Methods Non-inferiority of ACURATE neo2 vs Control for the primary Primary hypothesis endpoint of all-cause mortality, stroke or rehospitalization† at 1y • Non-inferiority test performed using Bayesian method; ITT population Expected rate 22.3% for both arms • Based on a weighted average
Slide 10: Trial Enrollment Timeline
Trial Enrollment Timeline • 1500 RCT subjects enrolled at 70 centers in United States and Canada • Enrollment occurred over a 47-month period, with higher risk patients enrolled earlier in the trial Total RCT Enrollment by Month & by Risk 80 # of RCT Randomizations (Enrollment) COVID (subsequent wav
Slide 11: ACURATE neo2 Implant Metrics
ACURATE neo2 Implant Metrics • Sites averaged 2.9 months between ACURATE neo2 implants • Total site volume of ACURATE neo2 cases was low 72% of physicians had 5 or fewer cases over the course of the trial Only 10% of implanters did more than 10 cases ACURATE neo2 Cases per Site 1% 9% 7.4% ≤ 10 c
Slide 12: Subject Disposition
Subject Disposition 1500 patients enrolled 1:1 Randomization ACURATE neo2 Control • Evolut (n=244) ITT Population (N=752) (N=748) • SAPIEN (n=504) (primary analysis population) No ACURATE neo2 Implanted (N=25) No Control Implanted (N=12) Withdrawal prior to procedure: 18 Withdrawal prior to procedur
Slide 13: Baseline Characteristics and Medical History
Baseline Characteristics and Medical History ACURATE neo2 Control Evolut SAPIEN (N=752) (N=748) (N=244) (N=504) Age (yrs) 78.0±6.9 (752) 79.0±6.5 (748) 78.8±6.0 (244) 79.1±6.8 (504) Female (%) 52.5% (395/752) 51.2% (383/748) 57.8% (141/244) 48.0% (242/504) STS Score (%) 2.7±1.8 (752) 2.8±1.9 (748) 2
Slide 14: Procedural Characteristics
Procedural Characteristics ACURATE neo2 Control Evolut SAPIEN P-value (N=244) (N=504) (N=752) (N=748) Correct positioning of a single valve into the proper anatomical location 98.4% (721/733) 99.1% (730/737) 0.243 97.5% (235/241) 99.8% (495/496) Prosthetic aortic valve malpositioning* 1.2% (9/752) 0
Slide 15: Primary Endpoint – Bayesian Analysis
Primary Endpoint – Bayesian Analysis Hypothesis Test in ITT population PE_ACURATE – PE_Control < Δ non-inferiority For the primary endpoint of all-cause mortality, stroke or rehospitalization† at 1 year Posterior Median and 95% BCI Non-Inferiority Test* Posterior Median Difference Non-inferiority AC
Slide 16: Kaplan-Meier Analysis through 1 Year
Kaplan-Meier Analysis through 1 Year ITT Population (N=1500) Death ∆1.1% Death, stroke, or rehospitalization† [-1.0%, 3.2%] 5.0% 3.9% ACURATE neo2 Control Stroke ∆2.3% [0.1%, 4.4%] ∆5.8% 5.7% [2.4%, 9.1%] 3.4% 14.8% 9.1% Rehospitalization† ∆1.8% [-0.4%, 3.9%] No. at risk ACURATE neo2 5.3% 752 733 71
Slide 17: Additional Safety Outcomes
Additional Safety Outcomes Time-to-Event Analysis through 1 Year Post-Procedure, ITT Population (N=1500) ACURATE neo2 Control Hazard Ratio Evolut SAPIEN (N=752) (N=748) [95% CI] (N=244) (N=504) Death 5.0% (36) 3.9% (28) 1.30 [0.80, 2.14] 3.4% (8) 4.1% (20) Cardiovascular death 3.7% (27) 1.8% (13) 2.
Slide 18: Echocardiography Outcomes
Echocardiography Outcomes Mean Gradient ACURATE neo2 neo2 (n=752) Paravalvular Regurgitation Severe Evolut (n=244) Moderate 16.0 SAPIEN (n=504) Mild 11.6 None/Trace 12.0 12.0 11.4 mmHg 9.0 8.0 Discharge 1 Year 8.0 8.2 7.7 7.9 7.0 0.1% 0.5% 4.0 1.0% 0.8% 3.2% 4.6% 0.2% 6.7% 23.0% 20.4% Discharge 30 D
Slide 19: Review of ACURATE neo2 Performance
Review of ACURATE neo2 Performance • Despite limited operator experience with ACURATE neo2, early outcomes were encouraging Periprocedural outcomes were favorable and comparable to Control Echo parameters (gradient and leak) were as expected No acute safety signals • COVID-related factors impa
Slide 20: Retrospective Review
Retrospective Review • A post-hoc case review of ACURATE neo2 implantation evaluated proper valve frame expansion per angiographic imaging ➢ Under-expansion can be identified by non-parallel commissure posts Valve frame under-expansion was present in ~20% of ACURATE neo2 cases
Slide 21: Bench Testing: Impact of Valve Frame Under-Expansion
Bench Testing: Impact of Valve Frame Under-Expansion Video Video Expanded ACURATE neo2 Max Velocity 1.6 m/s • Laminar flow • Adequate washout Video Video Under-Expanded ACURATE neo2 Max Velocity 3.1 m/s • Turbulent flow • Reduced washout
Slide 22: Post-Hoc Clinical Analysis: Valve Frame Expansion
Post-Hoc Clinical Analysis: Valve Frame Expansion Time-to-Event Analysis through 1 Year Post-Procedure (N=703) • Patients with under-expanded valves had increased rates of death (2-fold) and stroke (3-fold) compared to those with well-expanded valves ACURATE neo2 Expanded Under-Expanded Valve Frame
Slide 23: Post-Hoc Clinical Analysis: Valve Frame Expansion
Post-Hoc Clinical Analysis: Valve Frame Expansion Death, stroke, or rehospitalization† (N=1433) ACURATE neo2 Under-expanded ACURATE neo2 Expanded Control 18.8% 12.4% ∆3.4% [-0.1%, 6.8%] 9.1% No. at risk ACUR. neo2 Under-exp. (N=150) 150 150 144 135 132 121 ACUR. neo2 Expanded (N=553) 553 543 535 514
Slide 24: Post-Hoc Clinical Analysis: Valve Frame Expansion
Post-Hoc Clinical Analysis: Valve Frame Expansion ACURATE neo2 Under-expanded ACURATE neo2 Expanded Control Death Stroke 11.0% 7.4% 3.7% 3.5% 3.6% 3.4% Days since Procedure Days since Procedure No. at risk No. at risk ACUR. neo2 ACUR. neo2 150 150 149 147 145 135 150 150 146 137 136 123 Under-exp. U
Slide 25: ACURATE neo2 Under-Expansion: Potential Associations
ACURATE neo2 Under-Expansion: Potential Associations • Valve under-expansion has the potential to impact later clinical outcomes • Procedural technique may play a role Pre- and post-dilation was inconsistent with commercial practice due to use of smaller-than-recommended balloons, which has an imp
Slide 26: Importance of Post-Dilation: Proof of Concept
Importance of Post-Dilation: Proof of Concept ACURATE neo2 under-expansion can be easily recognized and is improved by post-dilation Valve under expanded with Post-dil resolves under-expansion Expanded valve with no angulated post evident & angulation of commissural post angulated post evident Video
Slide 27: Importance of Post-Dilation: Case Example
Importance of Post-Dilation: Case Example Under-expansion is easy to identify and correct during the procedure Video When is post dilation recommended? • Gradient ≥10mmHg ✓ • ≥ mild PVL ✓ • Valve under expansion • Identified by diameter or non-parallel posts (2nd view) • Easy to visualize on ACURATE
Slide 28: Study Limitations
Study Limitations • Trial-related factors First RCT experience with ACURATE neo2 enrolled patients of all risks Control arm included two comparator devices, with operator selection of preferred Control at time of randomization • Enrollment factors COVID – impact on staffing resources (hospital
Slide 29: ACURATE IDE Trial Key Take-Aways
ACURATE IDE Trial Key Take-Aways • The ACURATE IDE Trial is the largest head-to-head trial to evaluate TAVR with ACURATE neo2 Ability to compare ACURATE neo2 with commercially available devices was complicated by a challenging trial environment (trial-related and enrollment factors) • Post-hoc ana
Slide 30: Deep-dive session on the ACURATE IDE study
Deep-dive session on the ACURATE IDE study • Date/Time: Wednesday, October 30th 12:15-1:30 pm • Location: Presentation Theater #5 (FDA Theater) • Moderator: Michael Joseph Rinaldi • Faculty • Michael J. Reardon – A Closer Look at the ACURATE IDE Study • Ole de Backer – ACURATE IDE Insights: Optimizi