Radiofrequency Energy Provides Safe & Durable Blood Pressure Reduction: Complete 3 Year Results from Symplicity HTN-1 Henry Krum MBBS PhD FRACP FESC for the Symplicity I Investigators CCRE Therapeutics, Monash University, Melbourne, Australia
Disclosures Within the past 12 months, I or my spouse/partner have had a financial interest/arrangement or affiliation with the organization(s) listed below: Affiliation/Financial Relationship Company Grant/Research Support Medtronic
Background Percutaneous renal denervation (RDN) has been observed to reduce blood pressure (BP) short-term in patients with resistant hypertension Durability of BP reduction long-term post-rdn may be compromised by sympathetic nerve re-growth and possible functional re-innervation Furthermore, long-term safety and late complications of the RDN procedure need to be closely followed We therefore evaluated the long-term safety and BPlowering efficacy amongst all patients followed out to 36 months in the Symplicity HTN-1 study
Renal Nerve Anatomy Allows a Catheter-Based Approach
Symplicity HTN-1
Symplicity HTN-1 Hypertension. 2011;57:911-917. Catheter-based Renal Sympathetic Denervation for Resistant Hypertension Durability of Blood Pressure Reduction Out to 24 Months Symplicity HTN-1 Investigators*
Symplicity HTN-1 Study Centres The John Paul II Hospital, Krakow, Poland Prairie Education and Research Cooperative, Springfield, IL, USA Universitätsklinikum des Saarlandes, Homburg, Germany Samodzielna Pracownia Hemodynamiczna, Warsaw, Poland The Alfred Hospital, Melbourne, Australia CardioVascular Center Frankfurt, Frankfurt, Germany St. Vincent s Hospital, Melbourne, Australia Universitätsklinikum Düsseldorf, Düsseldorf, Germany MetroHealth System, Cleveland, OH, USA John Hunter Hospital, Newcastle, Australia Herz-Zentrum Bad Krozingen, Bad Krozingen, Germany Pauls Stradins Clinical University Hospital, Riga, Latvia Dedinje Cardiovascular Institute, Belgrade, Serbia Klinikum Coburg, Coburg, Germany Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany Hennepin County Medical Center, Minneapolis, MN, USA Universität Erlangen-Nürnberg, Erlangen, Germany Universität Leipzig Herzzentrum, Leipzig, Germany St. Josef und St. Elisabeth Hospital, Bochum, Germany Jerzy Sadowski Krishna Rocha-Singh Michael Böhm Andrzej Januszewicz & Adam Witkowski Henry Krum Horst Sievert Robert Whitbourn Lars Christian Rump Mark Dunlap Suku Thambar Thomas Zeller Andrejs Erglis Sagic Dragan Johannes Brachmann Gerhard Adam & Ulrich Wenzel Bradley Bart Roland Schmieder Dierk Scheinert Andreas Muegge
Patient Disposition Baseline 153 subjects enrolled Missing baseline BP (3)* 150 subjects evaluable for BP response 12 Month follow-up 132 24 Month follow-up 105 36 Month follow-up 88 Death (2) Withdrawal (4) LTFU (7) Missed/incomplete visit (5) Completed 12 month protocol (23) Death (1) Withdrawal (1) LTFU (1) Missed/incomplete visit (6) Completed 24 month protocol (12) Withdrawal (1) LTFU (4) Missed/incomplete visit (6)
Peri-Procedural Safety 38 minute median procedure time Average of 4 ablations per artery Intravenous narcotics & sedatives used to manage pain during delivery of RF energy No catheter or generator malfunctions Complications 4/153: 1 renal artery dissection during catheter delivery (prior to RF energy), no sequelae 3 access site complications, treated without further sequelae Symplicity HTN-1 Investigators, Hypertension. 2011
Baseline Patient Characteristics Full Cohort (n=153) Subject with 36 m follow up (n=88) Subjects w/out 36 m follow up (n=65) P- value Demographics Age (years) 57 ± 11 57 ± 11 57 ± 11 0.988 Gender (% female) 39 42 33 0.311 Race (% non- 5 5 5 1.00 Caucasian) Co-morbidities Type 2 Diabetes (%) 31 28 35 0.382 CAD (%) 22 23 20 0.843 Hyperlipidemia (%) 68 71 48 0.007 egfr (ml/min/1.73m 2 ) 83 ± 20 85 ± 19 82 ± 21 0.487 Blood Pressure Baseline SBP (mmhg) 175 ± 17 175 ± 13 178 ± 22 0.252 Baseline DBP (mmhg) 98 ± 15 97 ± 13 xx± xx 0.00x
Baseline Anti-Hypertensive Meds Full Cohort (n=153) Pts with 36 m follow up (n=88) Pts w/out 36 m follow up (n=65) P- value Number of anti-htn meds (mean±sd) 5.1 ± 1.4 5.16 ± 1.7 xx± xx 0.00x Diuretic (%) 95 93 86 0.00x Aldosterone blocker (%) 22 28 25 0.00x ACE/ARB (%) 91 0.00x Direct renin inhibitor (%) 14 18 14 0.00x Beta-blocker (%) 82 86 77 0.00x Calcium channel blocker (%) 75 80 77 0.00x Central sympatholytic (%) 33 38 32 0.00x
Change in Office BP Through 36 Months (All Patients) P<0.01 for from BL for all time points
Change in Office BP Through 36 Months (n=88) P<0.01 for from BL for all time points
Distribution of SBP Change (All Patients) % Patients (n=150) (n=141) (n=132) (n=105) (n=88)
Distribution of SBP Change (n=88) % Patients (N=88) (N=80) (N=85) (N=82) (N=88)
% Responders Over Time (All Patients)
% Responders Over Time (n=88)
Change in Office BP According to Baseline Renal function 12 Months 36 Months 24 Months mm Hg
Change in Office BP According to Age 12 Months 24 Months 36 Months (mm Hg)
Change in Office BP According to Diabetes Status 12 Months 24 Months 36 Months mmhg
bpm Heart Rate to 36 Months (All Patients)
Laboratory Results to 36-Months Mean SD Na+ (mmol/l) K+ (mmol/l) SCr ( mol/l) egfr (ml/min/1.73 m 2 ) Baseline 140.4 ± 3.9 (143) 3 Months 140.4 ± 3.1 (125) 6 Months 140.5 ± 3.2 (136) 12 Months 140.1 ± 3.3 (130) 24 Months 139.9 ± 3.0 (43) 4.1 ± 0.6 (145) 4.1 ± 0.5 (125) 4.1 ± 0.4 (136) 4.0 ± 0.4 (129) 4.1 ± 0.4 (43) 83.8 ± 20.1 (143) 85.8 ± 22.6 (132) 85.2 ± 20.1 (142) 85.4 ± 19.8 (130) 92.9 ± 29.8 (43) 83.6 ±19.7 (145) 82.6 ±21.0 (132) 82.6 ± 20.9 (142) 81.8 ± 19.5 (130) 76.8 ± 22.8 (43) 36 Months 139.7 ± 243 (29) 4.2 ± 0.9 (29) 92.0± 32.5 (28) 74.3 ± 28.0 (29)
Laboratory Results to 36-Months Mean SD Na+ (mmol/l) K+ (mmol/l) SCr ( mol/l) egfr (ml/min/1.73 m 2 ) Baseline 140.4 ± 3.9 (143) 3 Months 140.4 ± 3.1 (125) 6 Months 140.5 ± 3.2 (136) 12 Months 140.1 ± 3.3 (130) 24 Months 139.9 ± 3.0 (43) 4.1 ± 0.6 (145) 4.1 ± 0.5 (125) 4.1 ± 0.4 (136) 4.0 ± 0.4 (129) 4.1 ± 0.4 (43) 83.8 ± 20.1 (143) 85.8 ± 22.6 (132) 85.2 ± 20.1 (142) 85.4 ± 19.8 (130) 92.9 ± 29.8 (43) 83.6 ±19.7 (145) 82.6 ±21.0 (132) 82.6 ± 20.9 (142) 81.8 ± 19.5 (130) 76.8 ± 22.8 (43) 36 Months 139.7 ± 243 (29) 4.2 ± 0.9 (29) 92.0± 32.5 (28) 74.3 ± 28.0 (29)
36-Month Safety Possible Renal Artery Stenosis One progression of a pre-existing stenosis unrelated to RF treatment (stented without further sequelae) One new moderate stenosis which was not hemodynamically relevant, requiring no treatment One stenosis reported at 18 months via duplex found non significant at F/U angiography (20-30%) One right renal artery stenosis at 24 months successfully stented
36-Month Safety Possible Renal Artery Stenosis 0-6 Months > 6-18 Months > 18-36 Months Hemodynamically stable, no intervention required 1 1 - Stented without sequelae - - 1 Non-significant, no intervention required - 1 -
36-Month Safety Hypotensive episodes With renal failure (x2 patients), resolved Associated with severe diarrhoea and dehydration (x1) Two episodes orthostatic hypotension in 1 patient, both resolved Hypertensive episodes 13 subjects requiring hospitalization Death Myocardial infarction, after 3-day visit Sudden cardiac death, after 6 months Cardio-respiratory arrest, after 18 months
Summary The magnitude of BP-lowering with RDN in Symplicity HTN-1 is significant and sustained through 36 months, when all patients reaching this time-point are included This RDN BP-lowering clinical response was consistent across key subgroups (age, diabetes status, and baseline renal function) Very few clinically significant late adverse events related to RDN were reported through 36 months
Conclusions BP-lowering with percutaneous RDN appears to be durable out to 36-months This suggests that nerve re-growth and functional reinnervation do not translate into a clinically significant loss of BP-lowering efficacy of the procedure (at least to this time-point); further longer-term study of these patients required Analysis of key sub-groups did not demonstrate which patients may be hyper- or non-responders to the procedure; larger-scale studies eg registry data required