1 chronic treatment of resistant hypertension with an implantable medical device: interim 3 year...

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Chronic Treatment of Resistant Hypertension with an Implantable Medical Device: Interim 3 Year Results of Two

Studies of the Rheos® Hypertension System

Marcos Rothstein1, Peter de Leeuw2, Myriah Elletson3

for the DEBuT and Rheos Feasibility Investigators

1 Washington University School of Medicine

2Academisch Ziekenhuis Maastricht (AZM)

3 CVRx, Inc.

Confidential & Proprietary Information of CVRx Inc.2

Outline

• Background and rationale for the Rheos Hypertension System

• Study design and methods

• Interim clinical data on a device-based approach for treatment of drug resistant hypertension

• Conclusion and next steps for the assessment of chronic baroreflex activation as a potential new approach for the management of resistant hypertension and other conditions


Majority of US Hypertensive Patients Not at Systolic BP Goal of < 140 mmHg

3

HypertensiveN = 73.6 million

Aware (79%)57.9 million

Unaware (21%)15.7 million

Untreated (10%)7.1 million

Treated (69%)50.8 million

Controlled (45%)33.4 million

Uncontrolled (24%)17.4 million

40.2 million(55%) not at goal

D Lloyd-Jones et al., Circulation, Heart Disease and Stroke Statistics – 2009 Update: 6:e87-e95Based on Data from NHANES/NCHS 2005-2006


The CVRx® Rheos System

ImplantablePulse GeneratorImplantablePulse Generator

BaroreflexActivation LeadsBaroreflexActivation Leads

ProgrammingSystem

ProgrammingSystem


Comprehensive Mechanism of Action


Ability to Personalize and Control the Therapy


Feasibility Trial Design

• Subjects implanted at both European and US centers

– Multi-drug resistant systolic hypertension (SBP > 160 mmHg)

– 3+ anti-hypertensive medications with 1 diuretic

– Must not have hypertension secondary to a treatable cause

– Anti-hypertensive medications constant during the first 3 months of active treatment per protocol design

– Continued annual follow-up

BaselineImplant

-1 0 1 2 3 4 12 24

Months


Baseline Characteristics (N=38)

Location 25 Europe, 13 US

Gender 17 female, 21 male

Race 32 Caucasian, 5 African American

Age (mean years ± sd) 53 ± 11

# Antihypertensive Meds (mean ± sd) 5.1 ± 2

Antihypertensive Therapeutic Index 35.8 ± 17

OC Systolic BP (mean mmHg ± sd) 183 ± 27

OC Diastolic BP (mean mmHg ± sd) 105 ± 21

OC Heart Rate (mean bpm ± sd) 78 ± 12

OC = Office Cuff


Baseline Medications

Medication Class %

Diuretic 100 %

ACE Inhibitor/A2 Receptor 89

Beta Blocker 81

Calcium Channel Blocker - dihydropyridines 68

Other Sympatholytic 40

Alpha Blocker 39

Minoxidil 23

Calcium Channel Blocker – other 16


Office BP Response to Rheos Therapy

-35

-30

-25

-20

-15

-10

-5

0

1 Year (N=38)

2 Years (N=38)

3 Years (N=22)

Systolic(Baseline = 183 mmHg)

Diastolic(Baseline = 105 mmHg)

Heart Rate(Baseline = 78 BPM)

*p value < 0.001

† p value = < 0.005

† † p value = 0.15

Me

an

ch

an

ge

in

mm

Hg

or

BP

M

-25*

-22*

-31*

-15* -15*

-21*

-7 †-8 †

-5† †


Percentage of Subjects at Different Stages of Hypertension by Visit

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

Baseline 1 Year 2 Years 3 Years

SBP ≥ 160

SBP 140 - 159

SBP < 140


Change in Antihypertensive Therapeutic Index over Time

-12

-10

-8

-6

-4

-2

0

1 Year

Mea

n c

han

ge

in A

TI

-1

-5*

-11**

2 Years 3 Years

*p value = 0.05

**p value < 0.001


Diurnal Variation Preserved (24-hour Ambulatory, N=19)


Cardiac Structure and Function Improvements

N=18 Baseline Δ 12 Months

LV Mass Index (g/m2) 132.8 ± 33.3 –25.0 ± 18.2*

Left Atrial Dimension (mm) 44.1 ± 8.1 –2.4 ± 3.5*

Mitral E Wave Velocity (cm/s) 85 ± 19 –5 ± 14

Mitral A Wave Velocity (cm/s) 83 ± 22 –10 ± 13*

Bisognano JD. Journal of Cardiac Failure 2008;14(No. 6S Suppl):S48.

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

Baseline 12 Months

Severely Abnormal

Mildly or Moderately Abnormal

Reference Range

Values: mean ± SD *p value <0.05


Case ExampleLVMi and BP Reduction Following 3 Months of Rheos Therapy

Septal Wall Thickness = 1.16 cm

LV End-Diastolic Diameter = 5.16 cm

BP = 185/95 mmHg

ATI = 22.5 ; BMI = 34.4 kg/m2

Septal Wall Thickness = 0.90 cm

LV End-Diastolic Diameter = 4.12 cm

(SBP ↓ 30 mmHg, DBP ↓ 14 mmHg)

ATI = 22.5 ; BMI = 33.9 kg/m2

LVMI = 119.9 g/m2 LVMI = 97.0 g/m2

Pre-Implant 3-Months of Therapy


Case ExampleImproved LV Function After 3 Months of Rheos Therapy

Pre-Implant 3-Months of Therapy


Group B - Device OFF Group B - Device ON

Group A - Device ON Group A - Device ON

RandomizationImplant

FDA Approved Phase III Pivotal Clinical Trial

Long-TermFollow Up6-Month Evaluation Period

2:1 (Group A: Group B)

6-Month Blinded Evaluation Period

-1 0 6 12

• Prospective, randomized, double-blind, placebo-controlled, multi-center clinical trial

• Up to 300 patients, 50 medical centers

• Inclusion criteria: SBP ≥ 160 mmHg; 3+ medications

• Endpoint: % patients dropping > 10 mmHg with sustained reduction

Months


Conclusions

• Baroreflex hypertension therapy demonstrates clinically meaningful and sustained reduction in blood pressure in subjects with drug resistant hypertension

• The Rheos therapy also has been shown to improve cardiac structure and function – please visit poster 1051-168 at 9.30a on Tuesday 31 March 2009.

• These findings merit further investigation of this chronic device-based approach for hypertension management

• A randomized, blinded pivotal trial approved by FDA is underway


Acknowledgments• Inselspital Bern, Switzerland

• University Hospital Bad Oeynhausen, Germany

• Academisch Ziekenhuis Maastricht (AZM), The Netherlands

• Charité Campus Buch, Berlin, Germany

• Medizinische Hochschule Hannover

• Virginia Commonwealth University, Richmond VA

• University of Rochester, New York NY

• Washington University, St. Louis MO

• VA Medical Center, Washington DC

• Wayne State University

• Nebraska Heart Institute

CAUTION: CVRx Rheos System is an investigational device and is limited by Federal (or United States) law to investigational use only .

CVRx, Rheos, Baroreflex Hypertension Therapy are trademarks of CVRx, Inc. © CVRx, Inc. 2009.

1 chronic treatment of resistant hypertension with an implantable medical device: interim 3 year...

Documents

p value

hypertension secondary

oc systolic bp

oc diastolic bp

rheos therapysystolicbaseline

mmhg sd105

mmhg sd183

oc heart rate mean bpm