Slide 1: Preliminary Results of the Post-Market Phase of the BeAT-HF Randomized Clinical Trial
March 21, 2023 Preliminary Results of the Post-Market Phase of the BeAT-HF Randomized Clinical Trial
Slide 2: Forward-looking statements
2 Forward-looking statements This presentation contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements other than statements of historical facts are forward-looking statements, including statements regarding our future financial
Slide 3: BeAT-HF Executive Steering Committee
BeAT-HF Executive Steering Committee: Michael R. Zile JoAnn Lindenfeld Fred A. Weaver Faiez Zannad William T. Abraham Baroreflex Activation Therapy (BAT) in Patients with Heart Failure and a Reduced Ejection Fraction (BeAT-HF) Trial: Long – Term Outcomes Study Sponsor: CVRx
Slide 4: Disclosure Statement of Financial Interest
Within the past 12 months, I or my spouse/partner have had a financial interest/arrangement or affiliation with the organization(s) listed below. Affiliation/Financial Relationship Company Grant/Research Support NHLBI, VA, DOD Consulting Fees/Honoraria Abbott, Boston Scientific, CVRx, Corvia, Edward
Slide 5: Baroreflex Activation Therapy (BAT) Device (Barostim)
Carotid Sinus Lead • Extravascular • 2 mm electrode • Unipolar design • 5 year longevity • Personalized therapy • Average programming at 6 Mo: • 8.4 mA amplitude • 107 ms duration • 43 pps frequency IPG Baroreflex Activation Therapy (BAT) Device (Barostim) Heart Rate Remodeling Diuresis Renin Secret
Slide 6: BeAT-HF Trial Design
Prospective, multicenter, randomized, 2-arm, parallel-group, open-label with blinded evaluation trial Groups: - BAT plus optimal medical management (BAT group) - Optimal medical management alone (Control group) Sites: 103 US centers and 5 United Kingdom centers Eligibility criteria: - NYHA Class III
Slide 7: BeAT-HF Trial Design: Pre-Market and Post-Market Phases
Pre-Market Phase (n=264) Primary endpoint @ 6 months: • Exercise capacity improvement (6MHW) • Quality-of-life improvement (MLWHQ) • NYHA class improvement • Reduction in NT-proBNP Control 134 BAT 130 Post-Market Phase (additional n=59) Primary endpoint: CV mortality and HF morbidity Pre-specified a
Slide 8: BeAT-HF Baseline Characteristics
Baseline Characteristics BAT (n=163) Control (n=160) Age at Screening (years) 63 ± 11 63 ± 10 Female 28 (17.2%) 35 (21.9%) Race White 120 (73.6%) 116 (72.5%) Black or African American 29 (17.8%) 24 (15.0%) Asian 3 (1.8%) 2 (1.3%) Other/Unknown 11 (6.7%) 18 (11.3%) SBP (mmHg) 120 ± 16 121 ± 16 DBP (m
Slide 9: BeAT-HF Baseline Characteristics
Baseline Characteristics BAT (n=163) Control (n=160) Coronary Heart Disease Coronary Artery Disease 104 (63.8%) 107 (66.9%) Myocardial Infarction 89 (54.6%) 97 (60.6%) CABG 35 (21.5%) 44 (27.5%) PCI 72 (44.2%) 72 (45.0%) Cardiac Arrhythmia Bradycardia 19 (11.7%) 18 (11.3%) Tachycardia 54 (33.1%) 56
Slide 10: BeAT-HF Baseline HF Treatment
Baseline Medications BAT (n=163) Control (n=160) Number of Meds 4.0 ± 1.3 4.1 ± 1.5 ACE-I / ARB / ARNI 143 (88%) 129 (81%) ARNI 57 (35%) 43 (27%) Beta-Blocker 152 (93%) 147 (92%) MRA 74 (45%) 64 (40%) SGLT2i 1 (0.6%) 0 (0%) Diuretic 138 (85%) 139 (87%) Ivabradine 4 (2.5%) 9 (5.6%) ICD 125 (77%) 127
Slide 11: Study Endpoints
Cardiovascular (CV) Mortality And Heart Failure (HF) Morbidity • Assessed using a negative binomial model • Includes recurrent HF morbidity events • Pre-specified event–driven (n=320 events minimum) CV Mortality: • Cardiovascular deaths • LVAD and heart transplants HF Morbidity: • Non-elective HF ho
Slide 12: BeAT-HF Summary of Key Evidence
Description Composite CV Mortality and HF Morbidity Rate Ratio = 0.94 CV Mortality (CV death, LVAD, heart transplant) Hazard Ratio = 0.73 HF Morbidity (Heart failure hospitalization, ER/ED visit) Rate Ratio = 1.08 All-cause Mortality (death, LVAD, heart transplant) Hazard Ratio = 0.66 Hierarchical W
Slide 13: Primary Composite Endpoint: CV Mortality and HF Morbidity
No statistically significant difference between BAT and Control 0 0.5 1 1.5 2 0 1 2 3 4 RR* 0.94 (95% CI 0.57, 1.57); p=0.82 Control BAT BAT: N = 163 151 140 100 61 Control: N = 160 141 121 87 51 years Primary Composite Endpoint: CV Mortality and HF Morbidity Cumulative events per patient* * Cumulat
Slide 14: Components of Primary Endpoint
0 0.2 0.4 0.6 0.8 1 1.2 1.4 1.6 1.8 2 0 1 2 3 4 0.00 0.05 0.10 0.15 0.20 0.25 0.30 0.35 0.40 0 1 2 3 4 HR 0.73 (CI 95% 0.46, 1.17) nominal p=0.19 RR 1.08 (CI 95% 0.63, 1.84) nominal p=0.78 Control BAT Control BAT Event rate per 100 years (events / patient-years at risk) BAT Control CV Mortality 5.8
Slide 15: Hierarchical Composite Using Win Ratio Analysis
Rationale: • CV Mortality + HF Morbidity: 40% of patients contributed to the end point • Win ratio: 100% of patients contribute to the end point • Used in many recent heart failure randomized controlled trial, drugs and devices Stats: Finkelstein - Schoenfeld Hierarchical Composite Using Win Ratio A
Slide 16: Hierarchical Composite Using Win Ratio Analysis
Win Ratio = 1.26 (1.02, 1.58) nominal p-value = 0.04 BAT Control BAT Control 0 5000 10000 15000 Total Total Wins Hierarchical Composite Using Win Ratio Analysis 0 5000 10000 15000 Total Mortality Morbidity Symptoms CV Mortality 34% HF Morbidity 30% Quality of Life 37% * Sensitivity Test (All time M&
Slide 17: Freedom From All-cause Death, LVAD, and Transplant
0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% 0 1 2 3 4 HR 0.662 (95% CI 0.435, 1.007); nominal p=0.054 Freedom from all-cause death, LVAD and transplant BAT N = 163 151 140 100 61 CONTROL N = 160 141 121 87 51 BAT resulted in a 34% reduction in relative risk Control BAT Event rate per 100 years (even
Slide 18: Durable Safety Profile: MANCE
Number of Subjects Number of Subjects MANCE-Free MANCE-Free Rate One-Sided 95% Lower Bound P-value** 159 154 96.9% 93.5% <0.001 Durable Safety Profile: MANCE* (Major Adverse Neurological or Cardiovascular system or procedure-related event rate) Device was surgically implanted in an outpatient proced
Slide 19: Durable Improvement in Quality of Life (MLWHF)
6 months 12 months 24 months Durable Improvement in Quality of Life (MLWHF) *Statistics are estimated mean improvement and 95% confidence interval from repeated measures model **From generalized estimating equation repeated measures model with covariate for baseline value -19.8 -17 -18 -6.3 -8.6 -8
Slide 20: Durable Improvement in Exercise Capacity (6MHWD)
*Statistics are estimated mean improvement and 95% confidence interval from repeated measures model **From generalized estimating equation repeated measures model with covariate for baseline value 46.8 40.6 -8.7 -3 55.5 43.5 -40 -20 0 20 40 60 80 6 months 12 months BAT Control Diff** BAT Control Dif
Slide 21: Durable Improvement in Functional Status (NYHA Class)
66.6% 72.7% 68.0% 36.8% 40.8% 41.1% 29.8% 31.9% 26.9% 0% 10% 20% 30% 40% 50% 60% 70% 80% Durable Improvement in Functional Status (NYHA Class) 6 months 12 months 24 months NYHA Class* (% of Patients Improved by at least one class) *nominal p-value < 0.001 for between group differences at all time po
Slide 22: Totality of Data Favors BAT
Totality of Data Favors BAT BeAT-HF Summary of Key Evidence Description Composite CV Mortality and HF Morbidity Rate Ratio = 0.94 CV Mortality (CV death, LVAD, heart transplant) Hazard Ratio = 0.73 HF Morbidity (Heart failure hospitalization, ER/ED visit) Rate Ratio = 1.08 All-cause Mortality (death
Slide 23: Conclusion
Conclusion Totality of evidence indicates that BAT is a safe, effective and durable treatment for patients with heart failure with reduced ejection fraction
Slide 24: Additional Excerpts from the Symposium
CVRx-Sponsored Lunch Symposium at 12:15 – 1:15 pm Grand Ballroom A-B, Concourse Level an in-depth discussion on the findings from BeAT-HF and potential confounders (COVID-19, Medications) and real-world experience using Barostim Presented by: • William T. Abraham • JoAnn Lindenfeld • Patrick J. McCa
Slide 25: Clinical Stability Analysis
Improved: • Subject does not meet any worsening category AND • Fewer HF hospitalizations in 12 months post-enrollment vs 12 months pre-enrollment, • OR improved NYHA class at 12 months vs. baseline; Same: • Neither worsened nor improved • AND evaluable for both HF hospitalizations and NYHA; Worsened
Slide 26: Hierarchical Composite Using Win Ratio Analysis
Win Ratio = 1.26 (1.02, 1.58) nominal p-value = 0.04 BAT Control BAT Control 0 5000 10000 15000 Total Total Wins Hierarchical Composite Using Win Ratio Analysis 0 5000 10000 15000 Total Mortality Morbidity Symptoms CV Mortality 34% HF Morbidity 30% Quality of Life 37% * Sensitivity Test (All time M&
Slide 27: Sensitivity Analysis – All-Cause Mortality Win Ratio
0 5000 10000 15000 Total All Mortality HF Morbidity Quality of Life Win Ratio = 1.27 (1.02, 1.59) nominal p-value = 0.04 Total Wins All Mortality, 41% HF Morbidity, 24% Quality of Life, 35% BAT CONTROL Sensitivity Analysis – All-Cause Mortality Win Ratio
Slide 28: Primary Composite Endpoint: CV Mortality and HF Morbidity
0 0.5 1 1.5 2 0 1 2 3 4 RR* 0.94 (95% CI 0.57, 1.57); p=0.82 Control BAT BAT: N = 163 151 140 100 61 Control: N = 160 141 121 87 51 years Primary Composite Endpoint: CV Mortality and HF Morbidity Cumulative events per patient* * Cumulative events per patient and rate ratio (RR) of treatment / contro
Slide 29: Primary Composite Endpoint at 12 and 24 Months
0 0.2 0.4 0.6 0.8 1 0 1 2 24 Months: RR* 0.82 (95% CI 0.43, 1.57) Control BAT BAT: N = 163 151 140 Control: N = 160 141 121 years Primary Composite Endpoint at 12 and 24 Months Cumulative events per patient* * Cumulative events per patient and rate ratio (RR) of treatment / control and 95% confidenc
Slide 30: Impact of COVID-19 Pandemic on HF Morbidity
0 0.05 0.1 0.15 0.2 0.25 1-Jan-17 1-Jan-18 1-Jan-19 1-Jan-20 31-Dec-20 474 PATIENT-YEAR OF FOLLOW-UP (46%) 249 PATIENT-YEAR OF FOLLOW-UP (24%) 313 PATIENT-YEAR HF morbidity rate per patient OF FOLLOW-UP (30%) -year * *Normalized by total patient-years of follow-up per arm (BAT: 544 patient-years, Co
Slide 31: Potential Confounder: Impact of COVID Pandemic
Potential Confounder: Impact of COVID Pandemic Time Period BAT † Control† 2020 0.28 0.07 2016, 2017, 2018, 2019, 2021, 2022 0.26 0.29 † Number of hospitalizations or emergency department visits for heart failure per patient-year of follow-up Heart Failure Morbidity • COVID definitely impacted the re
Slide 32: Totality of Data Favors BAT
Totality of Data Favors BAT BeAT-HF Summary of Key Evidence Description Composite CV Mortality and HF Morbidity Rate Ratio = 0.94 CV Mortality (CV death, LVAD, heart transplant) Hazard Ratio = 0.73 HF Morbidity (Heart failure hospitalization, ER/ED visit) Rate Ratio = 1.08 All-cause Mortality (death
Slide 33: Conclusion
Conclusion Totality of evidence indicates that BAT is a safe, effective and durable treatment for patients with heart failure with reduced ejection fraction
Slide 34: Key takeaways
34 The post-market phase of BeAT-HF confirmed the long-term durability of safety and symptomatic improvements, and the sustainability of the extent of the improvements. The reduction of all-cause death, LVAD and heart transplant is meaningful (34% reduction, nominal p-value 0.054). The pre-specified
Slide 35: Next steps
35 One or more manuscripts will be written by the executive steering committee for submission to peer-reviewed journals The PMA Clinical report is being prepared by CVRx to be submitted to FDA, to seek an expansion of the labeling, commensurate with the recommendation of the Executive Steering Commi
Slide 36: Questions?
Barostim” Questions? Bane ames