Baroreflex Activation Therapy: Integrated Autonomic Neuromodulation for Heart Failure and Hypertension

Transcription

1 Baroreflex Activation Therapy: Integrated Autonomic Neuromodulation for Heart Failure and Hypertension Robert S. Kieval, VMD, PhD Founder & Chief Technology Officer, CVRx, Inc.

2 Financial Disclosure I, Robert Kieval, am an employee of CVRx, Inc.

3 Autonomic Dysregulation in Heart Failure Progressive Autonomic Imbalance Healthy Heart Failure Adapted from Robinson et al, 1966

4 The Baroreflex Provides Integrated Autonomic Neuromodulation BARORECEPTOR AFFERENTS CNS Vagus Nerve EFFERENTS Parasympathetic Sympathetic Adverse Cardiac Effects Heart Rate Arterial Baroreceptors Renal Sympathetic Nerves Na + Reabsorption Renin Renal Vascular Resistance Stiffness and Peripheral Vascular Resistance Adapted from Floras, J Am Coll Cardiol 2009 Heitz and Brody, 1973

5 A Unique Therapeutic Target for Heart Failure and Hypertension Programmable Baroreceptor Activation Brain Autonomic Nervous System Reduced Sympathetic Activity Enhanced Parasympathetic Activity Heart - Heart rate - Irritability Vessels + Vasodilation - Stiffness + Venous capacitance Kidneys + Diuresis + Natriuresis - RAAS activity myocardial work and oxygen consumption neurohormonal activation arrhythmogenesis excessive blood pressure

6 The Barostim neo Technology Platform 7 mm 2 mm Electrode Wireless Programmer Baroreflex Activation Lead Total Patients Treated with BAT Implantable Pulse Generator

7 Effects of Baroreflex Activation Dose-related and reversible The Baroreflex remains intact and responsive during therapy 63 yo female Delius et al, 1973

8 ABP [mmhg] MSNA [%] Cardiac and Peripheral Vascular Effects 250 Modulation of Sympathetic Nerve Activity 68 yo female Reduced arterial stiffness and wave reflections 63 yo female Control Barostim OFF ON OFF ON OFF Heusser et al, 2010 Time [mins] Georgakopoulos et al, 2011 Improved Sympatho-Vagal Balance Normalization of LV Pressure-Volume Relationship 73 yo male Wustmann et al, 2009 Hasenfuss et al, 2011

9 Clinical Evidence Development Stage Heart Failure: CE-Approved Hypertension: CE-Approved Clinical Rationale Preclinical First In Man CE Mark / Phase II US Phase III Pivotal Georgakopoulos et al, J Cardiac Fail 2012 Sabbah et al, Curr Cardiol Rep 2012 Halbach et al, Expert Rev Cardiovasc Ther 2014 Zucker et al, Hypertension 2007 Sabbah et al, Circ Heart Failure 2011 Liao et al, J Cardiovasc Pharmacol 2014 Brandt et al, Clin Res Cardiol 2010 Madershahian et al, Europace 2014 Gronda et al, Eur J HF 2014 Abraham et al, ACC Featured Clinical Research, March 2015 Zile et al, HRS Late Breaking Clinical Trials, May 2015 Zile et al, ESC-HF Late Breaking Clinical Trials, May 2015 Abraham et al, J Am Coll Cardiol HF 2015 Zile et al, Eur J Heart Failure 2015 Clinical trial fully FDA-approved Randomized, controlled clinical trial; n = 480 Composite of CV death and HF hospitalization Ram VS, J Clin Hypertension 2010 Briasoulis A, Bakris G, Eurointervention 2013 Borisenko et al, J Hypertension 2013 Lohmeier et al, Hypertension 2004, 2005, 2009, 2011, 2012 Schmidli et al, Vascular 2007 Mohaupt et al, Hypertension 2007 Illig et al, J Vasc Surgery 2006 Wustmann et al, Hypertension 2009 de Leeuw et al, JACC 2010 Heusser et al, Hypertension 2010 Bisognano et al, JACC 2011 Bakris et al, JASH 2012 Hoppe et al, JASH 2012 Wallbach et al, Am J Nephrol 2014 de Leeuw et al, Hypertension 2014 Clinical trial fully FDA-approved RCT; n = 240

10 Percent Free from Complication Clinical Results in Resistant Hypertension Safety of the Barostim neo Hoppe et al, 2012 Days from Implant % of patients at or below goal BP Sham-controlled results of BAT at 6 months Bakris et al, 2014 BAT Control per QALY gained Borisenko et al, 2013 Bisognano, et al, 2011 Bisognano et al, 2011

11 Heart Failure: US & European Randomized, Controlled, Clinical Trial n = 146 NYHA III LVEF 35% 6-month results in all patients Difference p value Favors NYHA (% improved) 31 < 0.01 Barostim MLWHF QoL Score (points) 20 <0.001 Barostim 6-MHW Distance (m) 58 <0.01 Barostim 100 MANCE NT-proBNP (pg/ml, median) Barostim LVEF (absolute %) Barostim Hospitalization Days for Worsening HF (days/pt/yr) Barostim Abraham et al, Event-free Rate (%) 97% event free 2 pocket hematomas Prospectively-defined non-crt vs. CRT analysis Measure Estimate p value Favors MLWHF QoL Score (points) Non-CRT 6MHWD (meters) Non-CRT NT-proBNP (pg/ml) Non-CRT LVEF (absolute %) Non-CRT # HF Hospitalization Days Non-CRT Zile et al, 2015

12 Regulatory Status in Heart Failure NYHA functional Class III FDA-approved Phase III Pivotal Clinical Trial Left ventricular ejection fraction 35% Despite guideline-directed therapy Morbidity & mortality design Expedited Access Pathway designation Narrow QRS Concomitant treatment with CRT Concomitant ICD Atrial Fibrillation NYHA III, LVEF 35% Non-CRT eligible or treated Concomitant ICD Atrial Fibrillation

13 Summary of Barostim Therapy Targeted and specific with favorable procedural and therapy safety Provides integrated autonomic neuromodulation: SNS + PNS Demonstrated mechanisms of action and physiologic effects Positive 5-year clinical results in resistant hypertension Positive 146-patient RCT in heart failure; outcomes trial approved A new treatment alternative for CRT-ineligible patients The Barostim neo System is CE Marked for the treatment of heart failure and for the treatment of resistant hypertension CVRx, Medicine Re-Envisioned, Rheos, Barostim, NEO, BAT and HOPE4HF are trademarks of CVRx, Inc. CVRx, Inc All rights reserved.