1. Prairie Cardiovascular, Springfield, IL US
Pooled 3-year SYMPLICITY HTN-1 And SYMPLICITY HTN-2 Results And Diabetes Subgroup Analysis
Richard Katholi, M.D
Prairie Cardiovascular, Springfield, IL US
On behalf of Murray D. Esler, Henry Krum, Krishna Rocha-Singh, Markus P. Schlaich, Michael Böhm, Felix Mahfoud, and the SYMPLICITY HTN Investigators
Murray Esler, Baker IDI Heart and Diabetes Inst, Melbourne, Australia; Henry Krum, Monash Univ/Alfred Hosp, Melbourne, Australia; Markus Schlaich, Baker IDI Heart and Diabetes Inst, Melbourne, Australia; Michael Böhm, Univsklinium des Saarlandes, Homburg, Germany; Roland E Schmieder, Univ Erlangen-Nürnberg, Erlangen, Germany

2. Catheter-Based Radiofrequency Renal Nerve Ablation
Interventional technique
4-6 two-minute treatments per artery
Proprietary RF Generator
Automated
Low-power
Built-in safety algorithms 2

3. SYMPLICITY HTN-1 and SYMPLICITY HTN-2: Study Designs
SYMPLICITY HTN-1:1 Prospective, International, Multicenter, Nonrandomized, Open-Label Study
Patients with Resistant Hypertension
Renal denervation with standard of care treatment* (N=153)
Mean age: 57 years
Mean baseline BP: 176/98 mm Hg
Mean no. antihypertensive medications: 5.1
Primary efficacy measure: Change in office BP
Primary safety assessments: Physical examination, blood chemistries; anatomic assessment of renal vasculature
SYMPLICITY HTN-2:2 Prospective, International, Multicenter, Randomized Controlled Trial
Renal denervation with standard of care treatment* (n=52)
Patients with Resistant Hypertension
KEY POINTS
SYMPLICITY HTN-1
The SYMPLICITY HTN-1 trial was a multicenter, open-label, nonrandomized, 36-month study of 153 patients with treatment-resistant hypertension who were enrolled between June 6, 2007 and May 1, The 19 investigational sites were located in Europe, Australia, and the United States
All 153 patients underwent endovascular catheter-based RDN. The primary objectives of the study were to assess changes in office BP and safety evaluations. Safety assessments were based on physical examination, basic blood chemistries, and anatomic assessments of renal vasculature, conducted via renal magnetic resonance angiography (MRA), computed tomography angiography (CTA), or duplex ultrasound scanning
SYMPLICITY HTN-2
In the SYMPLICITY HTN-2 trial, patients with resistant hypertension (defined as a baseline SBP of ≥160 mm Hg [or ≥150 mm Hg for patients with type 2 diabetes] despite taking ≥3 antihypertensive drugs) were randomized to undergo renal denervation with continuation of previous treatment or to maintain previous treatment alone. The trial was conducted at 24 centers [SYMPLICITY HTN-2, p 1903/abs]
The primary end point was between-group changes in average office-based measurements of SBP from baseline to 6 months after randomization
Secondary end points included:
Acute procedural safety
Chronic procedural safety (reduction of eGFR by >25% or new stenosis >60% confirmed by angiogram at 6 months)
The composite of myocardial infarction, sudden cardiac death, new-onset heart failure, death from progressive heart failure, stroke, aortic or lower limb revascularizations, lower limb amputation, death from aortic or peripheral arterial disease, death from renal failure, hospital admission for hypertensive emergency, and hospital admission for atrial fibrillation
Additional measurements of BP reduction at 6 months
REFERENCES
SYMPLICITY HTN-1 Investigators; Krum H, Barman N, Schlaich M, et al. Catheter-based renal sympathetic denervation for resistant hypertension: durability of blood pressure reduction out to 24 months. Hypertension. 2011;57:
SYMPLICITY HTN-2 Investigators; Esler MD, Krum H, Sobotka PA, et al. Renal sympathetic denervation in patients with treatment-resistant hypertension (The SYMPLICITY HTN-2 Trial): a randomised controlled trial. Lancet. 2010;376:
Primary efficacy measure: Change in office SBP at 6 months†
Follow up to 24 months (RDN and Crossover control)3
Mean age: 58 years
Mean baseline BP: 178/97 mm Hg
Mean no. antihypertensive medications: 5.2
Randomization
Maintain previous treatment alone (n=54)
*Standard of care treatment consisted of continuation of previous antihypertensive medications
†Control patients offered RDN following 6 month primary endpoint
BP=blood pressure; SBP=systolic blood pressure.
1. Symplicity HTN-1 Investigators. Hypertension. 2011;57: ; 2. Symplicity HTN-2 Investigators. Lancet. 2010;376: Krum H ACC 2013.

4. HTN-1 & HTN-2: Total patients treated
SYMPLICITY HTN-1
N=153
SYMPLICITY HTN-2
RDN group n=49
Crossover group n=37
Total Patients Treated
N=239
(Diabetics = 79 Non diabetics = 160)

5. Change in Office BP for HTN-1 and HTN-2 Pooled data through 36 months (N=239)
(mm Hg)
P < 0.01 compared to baseline for all data points

6. Baseline Demographics for HTN-1 and HTN-2 Pooled Diabetic subset
Parameter
DM (n=79, 33%)
Non-DM (n=160, 77%)
Age (years)
61.0 ± 8.1*
55.5 ± 12.6*
CAD
19 (24.1%)
26 (16.3%)
Hypercholesterolemia
52 (65.8%)
85 (53.1%)
Body Mass Index (BMI) mg/dL
32.9 ± 5.2
31.7 ± 5.7
Gender (Female)
27 (34.2%)
69 (43.4%)
Race (Caucasian)
76 (96.2%)
154 (96.3%)
eGFR (mL/min/1.73m2)
80.5 ± 19.2
84.0 ± 20.1
SCr (μmol/L)
50.1 ± 43.9
53.4 ± 43.1
*Significant (p < 0.001) between group difference
Data are n (%) or mean ± SD

7. Baseline Characteristics for HTN-1 and HTN-2 Pooled Diabetic subset
Parameter
DM (n=79 )
Non-DM (n=160 )
Office SBP (mm Hg)
178.1 ± 20.1
178.3 ± 16.5
Office DBP (mm Hg)
92.8 ± 14.0*
100.8 ± 14.7*
Heart Rate (BPM)
72.7 ± 12.3
73.9 ± 14.2
Number of medications
5.2 ± 1.6
5.0 ± 1.7
* Significant (p < 0.001) between group difference
Data are mean ± SD

8. Change in Office SBP for HTN-1 and HTN-2 Pooled Diabetic subset
(n=76) (n=153)
(n=75) (n=153)
(n=75) (n=137)
(n=58) (n=116)
(n=44) (n=84)
(mm Hg)
P < 0.01 compared to baseline for all data points
NS between group difference in SBP

9. eGFR* for HTN-1 and HTN-2 Pooled Diabetic subset
Stage I
Stage II
Stage IIIa
(mL/min/1.73m2)
Stage IIIb
Stage IV
Stage V
ESRD
*eGFR for pooled patients only available through 12 months post procedure

10. Catheter-based RDN Safety for Pooled HTN-1 and HTN-2 patients (N=239)
Procedural
Groin haematoma, pseudoaneurysm (1.7%)
Renal artery dissection (0.8%)
Hypotension (0.8%)
Long-term through 36 months
No atherogensis or fibrotic stenosis in field of energy delivery
No renal artery aneurysm
No deterioration in renal function through 12 months
Hypotension episodes (2.1%) similar to subjects on antihypertensive medications

11. Conclusions
Pooled analysis of subjects from the SYMPLICITY HTN-1 and HTN-2 trials indicate that treatment with the Symplicity™ renal denervation system provided safe and sustained reductions in office BP through 36 months
Acute procedural adverse events observed in this cohort reflected those commonly observed with percutaneous access and catheter manipulation within the arteries
Long-term safety data analysis showed no renal artery abnormalities or loss of renal function
In this post-hoc analysis, further analysis by diabetes status at baseline revealed similar significant drops in SBP