1. The Vessix Global Clinical Program REDUCE-HTN: REINFORCE
Michael Weber, MD

2. Michael Weber, MD Disclosures
Consulting: Boston scientific, Medtronics, Ablative Solutions, ReCor, Novartis Research: Medtronics, Boston Scientific, ReCor, Ablative Solutions, Novartis, Boehringer Ingelheim

3. Boston Scientific Renal Denervation REDUCE-HTN Clinical Series
Multicenter, Non-randomized, feasibility
CE Mark and TGA Approval
N = 128
Multicenter, Non-randomized, post market surveillance
N = 100
Multicenter, randomized
N = TBD
Multicenter, Non-randomized, single cohort
REDUCE-HTN FIM
REDUCE-HTN PMS
TReatment of
rEsistant hypertension using a raDiofrequency percUtaneous transluminal angioplasty CathetEr
REDUCE-HTN:
REINFORCE
REDUCE-HTN Global Pivotal
REDUCE-HTN Regional Approvals

4. REDUCE-HTN FIM+PMS Vessix™ Renal Denervation System
Balloon-based technology
4 - 7 mm diameters
Helical pattern of bipolar RF electrodes
All electrodes are activated simultaneously
30 second treatment time
Temperature-control algorithm for energy delivery at 68°C
One button operation
7F compatible (Vessix Reduce™ Catheter)
* Vessix System is an investigational device and not available for sale in the US. CE Mark received 2012.

5. REDUCE-HTN FIM+PMS Reduction in Office Blood Pressure
The REDUCE-HTN FIM + PMS results showed significant and sustained blood pressure reductions through 24 months
P<.0001 for each timepoint vs baseline. Error bars represent 95% confidence bounds.
Sievert , H. TCT 2015.
* Vessix System is an investigational device and not available for sale in the US.

6. Safety Profile Through 24 Months
Serious Adverse Events
Procedure related serious adverse events (within 6M of procedure)
Event
Number of events
Number of patients
Onset
Hematoma 1
0 days
Vomiting
Bilateral flank pain
1 day
Femoral artery thrombus
Pseudoaneurysm at access site
3 days
Access site infection 2
6 and 31 days
Renal artery stenosis requiring treatment
6 months
Occurrence > 6 months post-procedure
4 patients had hypertensive emergencies unrelated to medication or non-compliance
Adjudicated as possibly related to the device because renal artery stenosis could not be ruled out due to lack of recent renal artery imaging
Sievert , H. TCT 2015.
* Vessix System is an investigational device and not available for sale in the US.

7. REDUCE-HTN: REINFORCE Study Principal Investigators:
US IDE Study
REDUCE-HTN: REINFORCE Study 
Renal Denervation Using the Vessix Reduce™ Catheter and Vessix™ Generator for the Treatment of HyperTensioN: REINFORCE
Principal Investigators:
Martin B. Leon, MD
Michael Weber, MD
* Vessix System is an investigational device and not available for sale in the US.

8. US IDE Study The REDUCE-HTN:REINFORCE study:
Intends to demonstrate the effects of renal denervation in the absence of potentially confounding antihypertensive medications
Includes an antihypertensive medication wash-out phase
Similar to pharmaceutical study designs looking at early efficacy (Phase II studies)

9. REDUCE-HTN: REINFORCE Study Overview
Prescreen
N=100 at up to 20 US sites
Informed Consent
Washout Period (4 weeks)
Final Eligibility Assessment
OSBP ≥150 and ≤180 mmHg
ASBP ≥135 and ≤170 mmHg
Vessix RDN
Masked Procedure
N=100
2:1 Randomization (RDN:Control)
Primary Follow-up Period – No Meds (unless rescue)
Visits: 2, 4 and 8 weeks
Primary Efficacy Assessment (ASBP) – 8 weeks
Procedural Safety Assessments – 4 weeks
Secondary Follow–up Period – Med Additions per Protocol
Visits: 12, 16, 20 and 24 weeks
Secondary Efficacy Assessment (ASBP) – 24 weeks
Safety Assessment – 24 weeks
Long-term Follow–up through 3 years

10. REDUCE-HTN: REINFORCE
Study Overview
Phase II Pilot study (n=100) with sham control (2:1 randomization) in early stage HTN
ABPM at baseline, 4, 8, 24 and 52 weeks
Primary (powered) efficacy assessment at 8 weeks
Drug washout prior to randomization in all patients
Minimizes confounding due to medication changes
Rescue therapy allowed by protocol, but will become a study endpoint
Treatment Assignment:
Test = renal denervation
Control = renal angiogram only (no active therapy)
Medication burden in test and control arms assessed during secondary follow-up period
Safety assessment at 6M

11. Barriers to Randomization (after consent)
Initial study sites were interventionalist-based and did not have direct access to hypertension patients, needed referrals or community advertising – Recently, experienced hypertension investigator sites have been added to the trial
Average 24-hour ASBP must be >135 mmHg and <170 mmHg after screening – several patients lost through this criterion
OSBP must be ≥150 mmHg and ≤180 mmHg based on an average of 3 blood pressure measurements after screening – another source of patient loss
Eligible patients have declined randomization (often due to uncertain support of referring physicians)
Unsuitable renal artery anatomy

12. Conclusion
REDUCE-HTN: REINFORCE is a trial designed to isolate and measure the effects of renal denervation
The Company has committed to completing enrollment for this trial in 2017 and will reach the study’s primary endpoint soon afterwards
NOTE: The Vessix Catheter for renal denervation is not approved for use in the United States. Boston Scientific makes no claims in the United States regarding this product.

13. IMPORTANT INFORMATION: These materials are intended to describe common clinical considerations and procedural steps for the on-label use of referenced technologies as well as current standards of care for certain conditions. Of course, patients and their medical circumstances vary, so the clinical considerations and procedural steps described may not be appropriate for every patient or case. As always, decisions surrounding patient care depend on the physician’s professional judgment in light of all available information for the case at hand.
BSC does not promote or encourage the use of its devices outside their approved labeling.
The presenter’s experience with BSC products may not be interpreted or relied upon to support clinical claims about BSC devices or product comparison claims regarding BSC and competitive devices. The experiences of other users may vary.
Results from case studies are not predictive of results in other cases. Results in other cases may vary.

14. REINFORCE Study Details
REDUCE-HTN: REINFORCE
Randomization
2:1 (Test:Control)
Test: Renal Denervation
Control: Masked Procedure (renal angiogram)
Key Inclusion Criteria
≥18 and ≤75
OSBP ≥150 mmHg and ≤180 mmHg based on an average of 3 office-based blood pressure measurements
Avg 24-hour ASBP ≥135 mmHg and ≤170 mmHg
For each kidney, a main renal artery, with or without accessory renal arteries, with diameter ≥3.0 mm and ≤7.0 mm and length ≥20.0 mm
Primary Efficacy Assessment
Mean reduction in average 24-hour ambulatory systolic blood pressure (ASBP) at 8 weeks post randomization
Safety Assessments
Safety Assessments analyzed at all follow-up time points:
All-cause death
Renal failure
Hospitalization for hypertensive crisis
Hospitalization due to severe hypotension/syncope
Additional Safety assessments completed at 4 weeks and 6 months
All Safety Assessments will be adjudicated by an independent Clinical Events Committee

15. Future of Renal Denervation Managing Variability
Solutions
Stable baseline (careful drug wash-in phase)
Ambulatory BP (fully automated and documented)
OBP Readings
Optimized catheter effects
Consistent operator technique
Catheter and
Technique
Phase II: Placebo controlled with no meds RCT (Stage I-II)
Phase III: Placebo controlled
with standardized meds RCT (Uncontrolled HTN)
Drug changes &
Compliance
* Vessix System is an investigational device and not available for sale in the US.

16. Boston Scientific Renal Denervation REDUCE-HTN Clinical Series
Multicenter, Non-randomized, feasibility
CE Mark and TGA Approval
N = 128
Multicenter, Non-randomized, post market surveillance
N = 100
Multicenter, randomized
N = TBD
Multicenter, Non-randomized, single cohort
REDUCE-HTN FIM
REDUCE-HTN PMS
TReatment of
rEsistant hypertension using a raDiofrequency percUtaneous transluminal angioplasty CathetEr
REDUCE-HTN:
REINFORCE
REDUCE-HTN Global Pivotal
REDUCE-HTN Regional Approvals

17. Boston Scientific Renal Denervation RELIEVE Clinical Series
Renal Denervation - Chronic Kidney Disease
Prospective, single-center RCT, 1:1 - 20pts
Status – Enrolling
IMPROVE-HF
Prospective, randomized, 1:1 – 70pts
Status - Enrolling
REDUCE-CAD – HTN with CHF, AF, or Diabetes
Prospective, observation study – 100 pts
Kidney
Disease
RELIEVE Clinical Series European Investigator Sponsored Research Collaboration for expanded disease states
Heart Failure
HTN with Comorbidities