Slide 1: Safety and Efficacy of BackBeat CNT in Patients with Hypertension: Final Results
Safety and Efficacy of BackBeat™ Cardiac Neuromodulation Therapy (CNT™) in Patients with Hypertension: Final Results of a Double-Blind Randomized Trial Karl-Heinz Kuck, MD On behalf of coauthors: Z. Kalarus, B. Merkely, P. Neuzil, M. Grabowski, G. Marinskis, A. Erglis, J. Kazmierczak, P. Mitkowski,
Slide 2: Disclosure Statement of Financial Interest
Disclosure Statement of Financial Interest I, (Karl-Heinz Kuck, MD) DO NOT have a financial interest/arrangement or affiliation with one or more organizations that could be perceived as a real or apparent conflict of interest in the context of the subject of this presentation. 2
Slide 3: BackBeat Cardiac Neuromodulation Therapy (CNT)
BackBeat™ Cardiac Neuromodulation Therapy (CNT™) • Cardiac pacing to reduce blood pressure through two mechanisms: ▪ Reduction in LV Filling (preload) to provide an acute effect ▪ Neuromodulation to maintain effect chronically (afterload) • Delivered via implantable pulse generator (IPG) using stand
Slide 4: BackBeat CNT Initial Target Population
BackBeat CNT Initial Target Population • Hypertension patients indicated for pacemaker >1M pacemaker implants globally per year >70% of pacemaker patients have hypertension • ~ 60% uncontrolled despite treatment Older, co-morbid population at increased risk of major events High rate of Isola
Slide 5: MODERATO I Study
MODERATO I Study • Prospective, single-arm study of 27 patients with hypertension (office BP >150 mmHg) despite two or more anti-hypertensive medications and an indication for a pacemaker Effect of BackBeat CNT on 24-hour ASBP Effect of BackBeat CNT on OSBP +12M +18M +24M +1M +3M +6M +1 Day +1M +3M
Slide 6: MODERATO II Study
MODERATO II Study • Prospective, multi-center, randomized, double-blind study of BackBeat CNT vs. Medical Therapy (Control) 9 sites in EU Pilot study to inform the design and power of the pivotal study • Objective: to assess the efficacy and safety of BackBeat CNT in reducing blood pressure in p
Slide 7: MODERATO II: Study Design
MODERATO II: Study Design 30-day Run-In (RI) 6 Month Follow-Up Post-Randomization (PR) Phase Standard Pacing only (No BackBeat CNT) Continue Med Therapy Day Time ASBP Moderato with Day Time ASBP ≥130 mmHg & BackBeat CNT ≥125 mmHg @ Randomization OSBP ≥ 140 Implant Week 3 mmHg No BackBeat CNT + Conti
Slide 8: MODERATO II: Main Patient Selection Criteria
MODERATO II: Main Patient Selection Criteria Inclusion Exclusion 1. ≥ 18 years of age 1. Permanent atrial fibrillation or significant paroxysmal 2. Requires the implant or replacement of a dual chamber atrial fibrillation pacemaker 2. LV ejection fraction <50% 3. Stable hypertension treatment with a
Slide 9: MODERATO II: Study Flow
MODERATO II: Study Flow Screened N=196 Screen Failure* N=128 Moderato Implant N=68 Excluded End Run-in Phase Day Time ASBP<125 mmHg N=21 Included Day Time ASBP≥125 mmHg N=47 Electronic Randomization blocked by site Control BackBeat CNT N=21 N=26 1 Patient Died +6 Months +6 Months N=20 N=26 *50 (39%)
Slide 10: Patient Demographics: No Significant Differences Between Groups
Patient Demographics: No Significant Differences Between Groups p-value Control BackBeat CNT (Control vs (n=21) (n=26) BackBeat CNT) Age 74.9 ± 8.5 73.2± 9.0 0.518 Gender 15 M / 6 F 15 M / 11F 0.375 Weight (kg) 88.5±16.0 86.1±17.5 0.63 LV EF (%) 58.4±4.9 59.8±6.3 0.414 Medical History Diabetes 9 (42
Slide 11: Patient Demographics: Blood Pressure Prior to Randomization
Patient Demographics: Blood Pressure Prior to Randomization Comparable Between Groups p-value Control BackBeat CNT Control vs (n=21) (n=26) BackBeat CNT Isolated Systolic HTN 71.4% 88.5% 0.263 Screening 24-Hr Ambulatory SBP 142.8±11.8 139.3±10.3 0.287 24-Hr Ambulatory DBP 75.2±9.8 73.8±5.0 0.533 AMB
Slide 12: Primary Efficacy Endpoint (ITT): Changes in 24-Hour ASBP
Primary Efficacy Endpoint (ITT) 24-Hour ASBP at 6 Months Post-Randomization vs. Week 3 Run-In Primary Efficacy Endpoint met: 8.1 +/-3.0, (p=0.01) Difference in BP Reduction at 6 Months -8.1±3.0 P=0.01 Changes in 24-Hour ASBP (mmHg) -3.1 24-Hour ASBP (mmHg) ± 9.5 P=0.17 6 months Post- Week 3 Run-In R
Slide 13: Primary Safety Endpoint (ITT)
Primary Safety Endpoint (ITT) MACE through 6 Months Post-Randomization Primary Safety Endpoint Met: No Difference in MACE at 6 Months 6 Month MACE* BackBeat CNT Control n 26 21 MACE 0 (0.0%) 2 (9.5%) Control MACE Patients • Pt 1: Death as a result of disseminated adenocarcinoma. Angina pectoris lead
Slide 14: Changes in OSBP (mmHg)
Office Systolic Blood Pressure (OSBP) 6 Months Post-Randomization vs. Week 4 Run-In Significant Difference Between BackBeat CNT and Control in OSBP Reduction: -12.3 +/-5.4 (p=0.02) -12.3±5.4 P=0.02 0 -0.1 OSBP (mmHg) -2 ± 21.9 Changes in OSBP (mmHg) 6 months Post- -4 P=0.94 Week 4 Run-In Randomizati
Slide 15: Changes in 24-Hour ASBP (mmHg)
24-Hour ASBP Post-Randomization vs. Week 3 Run-In ASBP Reduction Observed at Day 1 Post-Randomization and Maintained Through 6 Months +1Day +1 Month +6 Months -14.1 -6.6 -8.1 ±3.1 ±3.3 ±3.0 P<0.001 P=0.04 P=0.01 +1 Month0 -1.5 -3.1 Changes in 24-Hour ASBP (mmHg) ± 10.1 ± 9.5 P=0.5 -5.1 P=0.17 ± 12.4
Slide 16: BackBeat CNT Responder Analysis
BackBeat CNT Responder Analysis 6 Months Post-Randomization vs. Week 3 Run-In High Overall Response Rate to BackBeat CNT with 54% Experiencing >10 mmHg Reduction in ASBP Despite Lower Starting ASBP and High % ISH BackBeat CNT Control (n=26) (n=19) % with Increase in ASBP 15% 47% % with Reduction in
Slide 17: Changes in Medications Throughout the Duration of the Study
Changes in Medications Throughout the Duration of the Study Improvement in ASBP in the BackBeat CNT Group Not Driven by Increase in Medications BackBeat CNT Control n=26 n=21 Number of pts w/ changes in 3 (11.5%) 7 (33.0%) prescribed medications Increase Decrease Increase Decrease 2 (7.7%) 1 (3.8%)
Slide 18: Changes in Diastolic Blood Pressure, Heart Rate and Echo at 6 Months
Changes in Diastolic Blood Pressure, Heart Rate and Echo at 6 Months No significant differences in Diastolic Blood Pressure, Heart Rate or Echo Parameters (EF, EDV, ESV) between BackBeat CNT and control groups 18
Slide 19: MODERATO II Conclusions
MODERATO II Conclusions • In patients with arterial hypertension and an indication for a pacemaker, Backbeat CNT demonstrated: Significant reduction in mean ASBP and OSBP No difference in MACE No differences in diastolic blood pressure (DBP), heart rate (HR) or echo parameters High responder