the safety and long-term effect of renal artery denervation on blood pressure and renal function in...
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The safety and long-term effect of renal artery denervation on blood pressure and renal function
in real world patients with uncontrolled hypertension from the Global SYMPLICITY Registry
Felix Mahfoud, MD1
M. Böhm1, K. Narkiewicz2, L. Ruilope3, M. Schlaich4, R. Schmieder5, B. Williams6, G. Mancia7
on behalf of the GSR Investigators
1 Saarland University Hospital, Homburg/Saar, Germany2 Medical University of Gdansk, Gdansk, Poland; 3 Hypertension Unit, Hospital 12 de Octubre, Madrid, Spain; 4 Royal Perth Hospital Unit, The University of Western Australia, Perth, Australia; 5 Universität Erlangen Nürnberg, Nürnberg, Germany; 6 Institute of Cardiovascular Sciences,
University College London, London, United Kingdom; 7 University of Milano Bicocca, St Gerardo Hospital, Monza, Italy
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Potential conflicts of interest
Speaker's name: Felix MahfoudI have the following potential conflicts of interest to report:
Research Grants• Deutsche Hochdruckliga• Deutsche Gesellschaft für Kardiologie• Saarländisches Ministerium für Wissenschaft und Forschung
Consultant/Lecture fee/Travel support: • Medtronic, St. Jude, Boston Scientific, Cordis, Berlin Chemie,
Boehringer Ingelheim
Institutional grant/Research support: • Medtronic, St. Jude, Recor, Boston Scientific
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Background
• The Global SYMPLICITY Registry was designed to assess the procedural and long-term safety and effectiveness of the Symplicity™ renal denervation system in a real-world patient population of– patients with uncontrolled hypertension alone or – patients with concomitant conditions also characterized by
sympathetic nervous system overdrive
• Follow-up results of the first 2037 enrolled patients are available through 6 months, and 2-year outcomes are available for 608 enrolled patients.
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Global SYMPLICITY Registry (GSR) Current Activated Site Locations
CA: 5
MEA: 39
WE: 131
C&EEU: 19
ASEAN: 19
Korea: 10
247 sites in 37 countriesEnrollment to date: 2385 pts ANZ: 14
LA: 10
• 5000 real world patients with uncontrolled hypertension or other conditions associated with increased sympathetic activity
• >18 years
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Global SYMPLICITY Registry (GSR) Clinical Trial Design
• 40% randomly assigned to 100% monitoring
Max. 5000 patients
Böhm,M, et al. Hypertension. 2015
GREAT Registry
N=1000
Korea Registry
N=102
South Africa RegistryN=400
Canada & Mexico1
Rest of GSR
N≈3500
Prospective, open-label, single-arm, all-comer observational registry
6M 3Y2Y1YFollow-up 3M 4Y 5Y
1601
NCT01534299
2037 608Patient data availableto date
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Patient DispositionBaseline (N=2037)OBP: 1979 (97%)
ABPM: 1403 (69%)
6 Month Follow-up eligible (N=2037)Safety: 1983 pts (97%)OBP: 1571 pts (77%)
ABPM: 1045 pts (51%)
1 Year Follow-up eligible (N=1601)Safety: 1396 pts (87%)
OBP: 1444 pts (90%)ABPM: 932 pts (58%)
Analysis on BP change performed on patients with matching baseline and follow-up values
2 Year Follow-up eligible (N=608)Safety: 451 pts (74%)
OBP: 508 pts (84%)ABPM: 257 pts (42%)
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Baseline Patient Characteristics
% or mean ± SD N=2037
Male gender 59.1Age (years) 61 ± 12BMI (kg/m2) 31 ± 6Current smoking 9.6History of cardiac disease 48.2Chronic kidney disease (eGFR <60ml/min/1.73m2) 21.8Obstructive sleep apnea 11.0Sleep apnea (AHI≥5) 4.1Atrial fibrillation 12.8Diabetes, Type 2 38.11 co-morbidity 39.42 co-morbidities 36.93+ co-morbidities 23.7
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Baseline Patient Characteristics
% or mean ± SD N=2037
Office BP (Systolic/Diastolic), mmHg 165/89 ± 25/16
24-h BP (Systolic/Diastolic), mmHg 154/86 ± 18/14
True hypertension 82
Masked hypertension 12
Pseudo-hypertension 4
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Procedural Details
mean ± SD N=2037
Number of renal arteries 2.1 ± 0.5
Treatment time (min) 48.9 ± 20.4
Number of ablations 13.3 ± 4.0
Number of 120 sec ablations 11.3 ± 3.4
Contrast volume used (cc) 128.2 ± 77.8
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Anti-hypertensive Medication Use
% or mean ± SD Baseline 1 Year 2 Years P
Anti-hypertensive medication classes 4.5 ± 1.4 4.4 ± 1.4 4.4 ± 1.4 <0.0001
Beta-blockers 77.4 75.0 77.1 0.04
ACE inhibitors 34.2 31.1 28.9 <0.0001
Angiotensin Receptor blockers 65.5 65.1 66.7 NS
Calcium Channel blockers 78.3 76.1 76.9 NS
Diuretic 79.4 77.1 77.2 NS
Aldosterone antagonists 23.6 26.4 25.4 <0.0001
Spironolactone 20.1 22.1 20.9 0.006
Alpha-adrenergic blockers 34.3 32.1 32.6 0.002
Direct-acting vasodilators 13.7 13.4 14.7 NS
Centrally-acting sympatholytics 38.3 34.7 30.3 <0.0001
Direct renin inhibitors 6.3 5.0 5.6 0.0002
P-values calculated by Friedman test to compare medication rates across time points on repeated measures of patient level data.
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Safety Results to 2 Years% 6 Months
n=19271 Yearn=1383
2 Yearsn=425
Composite safety endpoint 2.3 4.0 8.0
Cardiovascular events
Cardiovascular death * 0.3 0.9 1.2
Stroke 0.8 1.4 2.6
Hospitalization for new onset heart failure 0.7 1.2 2.6
Hospitalization for atrial fibrillation 0.7 1.7 2.6Hospitalization for hypertensive crisis/hypertensive emergency * 0.8 1.5 3.8
Myocardial infarction 0.8 1.1 2.4
Renal events
New onset end-stage renal disease * 0.2 0.5 1.4
Serum creatinine elevation >50% 0.5 1.2 2.8
New artery stenosis >70% * 0.1 0.2 0.0
Post-procedural events
Non-cardiovascular death 0.1 0.4 1.4
Renal artery reintervention * 0.3 0.4 0.5
Vascular complication * 0.7 0.5 0.9
* Included in composite safety endpoint at 30 days
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BP Change at 6 Months
-20
-15
-10
-5
0
-12.3
-6.8
-4.5 -4.0
systolicdiastolic
Syst
olic
Blo
od P
ress
ure
Chan
ge
(mm
Hg)
Office BP 24h ABPM N = 1531 n=877
P < 0.0001 P < 0.0001
Baseline BP 165/89 ± 25/16 154/86 ± 18/14
n=878N = 1526
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Office Systolic BP Change
-20
-15
-10
-5
0
-12.3 -12.5-13.5
-14.8
Syst
olic
Blo
od P
ress
ure
Chan
ge
(mm
Hg)
All patients with ≥ 6mo f/u
n=1531
Baseline OSBP 164 ± 24 P < 0.0001
n=447n=447
Baseline OSBP 163 ± 22P < 0.0001
n=400
Change at 6 monthsChange at 1 yearChange at 2 years
All patients with 2yr follow-up
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24-h Ambulatory BP Change
-20
-15
-10
-5
0
-6.6 -7.1-8.1 -8.0
Syst
olic
Blo
od P
ress
ure
Chan
ge
(mm
Hg)
n=787 n=171n=195
Baseline ABPM 153 ± 18P < 0.0001
Baseline ABPM 152 ± 18P < 0.0001
n=186
All patients with ≥ 6mo f/u
All patients with 2yr follow-up
Change at 6 monthsChange at 1 yearChange at 2 years
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Office BP by Stratified GroupsChange to 2 Years
-40
-20
0
2013
-4
-15
-33
12
-4
-16
-34
10
-5
-19
-35
Syst
olic
Blo
od P
ress
ure
Chan
ge
(mm
Hg) OSBP <140
(N=271)
OSBP ≥180(N=513)206
128 ± 10P < 0.0001 at all timepoints
216
368179
168 ± 6P < 0.0001 at all timepoints
OSBP 160-179(N=654)
OSBP 140-159(N=541)
150 ± 6P ≤0.005 at
all timepoints
197 ± 15P < 0.0001 at all timepoints
418 529
66
384 140 476 116345
Change at 6 monthsChange at 1 yearChange at 2 years
Baseline OSBPP-value compared
to baseline BP
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24-h ABPM by Stratified GroupsChange to 2 Years
-20
-10
0
10
-5-6
-7-8
-4
-6-8
-11
-4
-8
-10-11
Syst
olic
Blo
od P
ress
ure
Chan
ge
(mm
Hg)
OSBP <140(N=271)
OSBP ≥180(N=513)
144 ± 16P <0.001 at 6M,
P=0.03 at 1yrP=NS at 2yrs
19364
155 ± 17P < 0.0001 at all timepoints
OSBP 160-179(N=654)
OSBP 140-159(N=541)
148 ± 15P <0.005 at
all timepoints
164 ± 19P < 0.005 at
all timepoints
246 269231 67 227 42162
Change at 6 monthsChange at 1 yearChange at 2 years
129145 36
Baseline ABPMP-value compared
to baseline BP
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Office Systolic BP
-30
-20
-10
0
-22.0
-12.8
-22.4
-16.7
-21.3
-17.3
Syst
olic
Blo
od P
ress
ure
Chan
ge
(mm
Hg)
Severe resistant HTNOSBP ≥ 160, ABPM ≥ 135
and 3+ meds(N=681)
Less severe HTNOSBP 150 – 180, ABPM 140 – 170
and DBP ≥ 90(N=213)
Baseline OSBP 181 ± 18P < 0.0001
n=531 n=165 n=51n=146
Baseline OSBP 165 ± 8P < 0.0001
n=484 n=153
Change at 6 monthsChange at 1 yearChange at 2 years
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Ambulatory Systolic BP
-20
-10
0
-8.5-7.4
-11.0 -10.9-11.0 -10.7
Syst
olic
Blo
od P
ress
ure
Chan
ge
(mm
Hg)
Baseline ABPM 161 ± 16P < 0.0001
n=403 n=133 n=36n=116
Baseline ABPM 154 ± 8P < 0.0001
n=344 n=93
Change at 6 monthsChange at 1 yearChange at 2 years
Severe resistant HTNOSBP ≥ 160, ABPM ≥ 135
and 3+ meds(N=681)
Less severe HTNOSBP 150 – 180, ABPM 140 – 170
and DBP ≥ 90(N=213)
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Conclusions
• The Global SYMPLICITY Registry is largest available real world database and has enrolled over 2300 patients to date.
• No long-term safety concerns have been observed following the denervation procedure.
• Renal denervation in a large real world population resulted in significant blood pressure reductions at 6 months that were sustained in the cohort that was followed out to 2 years post-procedure.