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Device Therapy
Paul A. Sobotka, MD
Professor of Medicine/Cardiology
The Ohio State University
Chief Medical Officer
Cibiem, Inc.
Disclosure Statement of Financial Interest
Within the past 12 months, I or my spouse/partner have had financial
interest/arrangement or affiliation with the organization(s) listed below.
Affiliation/Financial Relationship
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•
Consulting Fees/Honoraria
Royalty Income
Ownership/Founder/Salary
Company
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Ardelyx Inc.
Medtronic, Inc.
Rox Medical, Inc.
Ardian, Inc.
Cibiem, Inc.
Renal denervation in less severe
treatment resistant hypertension
• Christian Ott, Felix Mahfoud, Axel Schmid, Tilmann
Ditting, Paul A. Sobotka, Roland Veelken, Aline Spies,
Christian Ukena, Ulrich Laufs, Michael Uder, Michael
Bohm, Roland E. Schmieder
• Submitted
• Embargoed
Moderate Hypertension
• Device therapy for the treatment of hypertension
which is NOT proved unresponsive to diet, exercise
and medications
• Device therapy enabling treatment of the
persistently non compliant patient
• Device therapy as an empowering choice for patients
to select between treatment with a device and life
long poly pharmacy
Background Drug Therapy
• Proof of safety and efficacy requires stationary
background diet, exercise, and drug therapy
• Resistant hypertension
– Defines a subgroup of HTN patients who may derive
benefit from device intervention
• In the opinion of many HTN experts, device therapy should be
reserved for compliant patients who accept life long poly
pharmacy as a treatment strategy and whose physicians are expert
in using highest doses of several drugs used in combinations
untested and unproven safe and effective
rHTN- Patient Selection?
• What constitutes failed pharma therapy?
– 3 drugs, maximal doses (one being a diuretic)?
– 3 drugs, maximal doses (one being a diuretic),
one being spironolactone?
– Care provided by an HTN expert?
• Does patient choice matter?
– Does willful non-compliance with life long poly
pharmacy recuse patients from consideration?
Blood Pressure is a lousy way of
measuring hypertension
• Blood pressure is the product of cardiac
output, vascular capacitance, compliance,
reflection and resistance
– MI can cure high blood pressure but not
hypertension
• Blood pressure is dynamic; a single
measure cannot adequately characterize
vascular dynamics when at rest and when
under stress.
BP Syndromes
• Hypertension (mild, moderate, severe)
• White coat hypertension (hypertension only
when in the physicians office)
• Concealed hypertension (hypertension only
when at home)
• Episodic hypertension (malignant, crisis)
• Pseudo hypertension (something to do with
patient behaviors, or clinical failure to properly
measure)
New and novel devices must demonstrate safety and
define effectiveness to inform patient choice
• Special case of untreatable hypertension
– Above target despite diet/exercise/medication compliance
• To reduce calculated 10 year CV risk
• To attenuate or reverse end organ damage
• Special case of the persistently non compliant patient
• Universal case of empowering patient choice
Moderate vs Severe HTN
• The CV risk of hypertension is linear for all bp
above 140mmHg
• Restricting therapy to those with ULTRA
hypertension (>160 mmHg) versus those with
Moderate (140-160mmHg) is indefensible
– A 20 mmHg reduction of bp generates same benefit
for a patient with ultra and with moderate
hypertension
– A 20 mmHg reduction of bp attains infinite individual
and social benefit for the non compliant patient
Risk:Benefit Device Therapy HTN
Prevention
Symptom
reduction
Mortality reduction
Risk of native disease
Risk:Benefit Device Therapy HTN
Prevention
MHTN SHTN
rHTN
Symptom
reduction
Afib
Mortality reduction
CKD
CHF
Risk of native disease
Risk:Benefit Device Therapy HTN
Prevention
Symptom
reduction
Mortality reduction
CHF
CKD
Afib
Magnitude of benefit
SHTN
rHTN
MHTN
Risk of native disease
Risk:Benefit Device Therapy HTN
Prevention
Symptom
reduction
Mortality reduction
CHF
Afib
Magnitude of benefit
SHTN
rHTN
MHTN
CKD
Risk of native disease
Inherent Procedure
Risk
The benefit is related to the biologic limits
of improvements:
•
A patient with 180mmHg baseline can
experience a 40 mmHg reduction
•
A patient with a 160mmHg baseline can
experience only a 20 mmHg improvement
Vascular and Renal Safety
• Vascular Safety
– Acute Renal Artery structure and function
• Preclinical: structural integrity of artery
• Human: post procedure arterial imaging
– Chronic Renal Artery structure and function
• Preclinical: 3 month pig anatomy and histology
• Human: 6 month follow up demonstration of patency and lack of
therapy related aneurysms, or clinically important stenosis
• Renal Safety
– Human: serial tracking of changes in kidney function relative
to adequate control population (eGFR can hide mischief )
Clinical Endpoints
• Hypertension
– Refractory, resistant, difficult to treat, moderate, patient
preference (non compliance)
• Non Hypertension
– HFrEF, HFpEF, prevention or treatment of tachy atrial or
ventricular arrhythmias, ADHF, prevention of CKD
progression, SDB (central, obstructive), insulin
resistance…..
Terminal Thoughts