Transcript Change in blood pressure (mm Hg)

Reduced Blood Pressure Lowering Effect of
Catheter-Based Renal Denervation in Patients with
Isolated Systolic Hypertension: Data from Pooled
SYMPLICITY HTN Trials
Felix Mahfoud*, George L. Bakris, Deepak L. Bhatt, Murray D Esler, David E. Kandzari, Kazuomi
Kario, Henry Krum, Giuseppe Mancia, Ashok Seth, Michael A. Weber, Robert Whitbourn,
Michael Boehm
*Universitätskliniken des Saarlandes, Homburg/Saar, Germany
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Author Disclosures
Ashok Seth, M.B.B.S., F.A.C.C.
CONSULTANT FEES/HONORARIA - Abbott Vascular, Boston Scientific, Medicines Company, Medtronic,
Meril life sciences.
David E. Kandzari, MD, F.A.C.C. CONSULTANT FEES/HONORARIA - Boston Scientific, Medtronic, Micell Technologies, Thoratec.
Deepak L. Bhatt, MD, MPH,
F.A.C.C.
CONSULTANT FEES/HONORARIA - Elsevier Practice Update Cardiology; RESEARCH/RESEARCH GRANTS Amarin, Astra Zeneca, Bristol Myers Squibb, Eisai, Ethicon, FlowCo, Forest Laboratories, Ischemix, Inc,
PLx Pharma, Roche, Sanofi Aventis, Takeda, The Medicines Company; OTHER - Belvoir Publications,
Cardax, Clinical Cardiology, HMP communications, Journal of Invasive Cardiology, Medscape Cardiology,
Regado Biosciences, Slack Publications/Cardiology Research Foundation, WebMD.
Felix Mahfoud, M.D.
Nothing to Disclose
George L. Bakris, M.D.
CONSULTANT FEES/HONORARIA - AbbVie, Vascular Dynamic, Janssen, Eli Lilly, Novartis, Takeda, DSI,
Boeringher-Ingelheim, MedTronic, Relypsa, Bayer.
Giuseppe Mancia, M.D.
Nothing to Disclose
Kazuomi Kario, M.D., Ph.D,
F.A.C.C.
CONSULTANT FEES/HONORARIA - Astellas Pharma Inc., AstraZeneca K.K., Bayer Yakuhin Ltd., Boehringer
Ingelheim Japan Inc., Bristol-Myers K.K., Daiichi Sankyo Company, Limited., GlaxoSmithKline K.K., Kowa
Pharmaceutical Co. Ltd., Kyowa Hakko Kirin Co., Ltd., Medtronic Japan Co., Ltd., Mitsubishi Tanabe
Pharma Corporation., Mochida Pharmaceutical Co., Ltd, Otsuka Pharmaceutical Co., Ltd., Pfizer Japan
Inc., Roche Diagnostics K.K., Sanofi K.K., SANWA KAGAKU KENKYUSHO CO.,LTD., Shionogi & Co.,
Ltd., Sumitomo Dainippon Pharma Co., Ltd., Takeda Pharmaceutical Company Limited., Terumo
corporation.
Michael Boehm, MD
CONSULTANT FEES/HONORARIA - Astra Zeneca, Bayer AG, Boehringer Ingelheim, Daiichi-Sankyo,
Medtronic, MSD, Novartis, Pfizer, Sanofi-Aventis, Servier; RESEARCH/RESEARCH GRANTS - Astra Zeneca,
Bayer AG, Boehringer Ingelheim, Novartis, Pfizer, Sanofi-Aventis, Medtronic, Servier; SPEAKER’S BUREAU
- Astra Zeneca, Bayer, Boehringer Ingelheim, Berlin-Chemie, Daiichi-Sankyo, MSD, Novartis, Pfizer,
Sanofi-Aventis, Servier, St Jude, Medtronic.
Michael A. Weber, M.D.,
F.A.C.C.
CONSULTANT FEES/HONORARIA - Boston Scientific, MEDTRONIC, Novartis, Recor; SPEAKER’S BUREAU Arbor
Murray D Esler, M.B.B.S., Ph.D. CONSULTANT FEES/HONORARIA - Medtronic/Ardian; RESEARCH/RESEARCH GRANTS - Medtronic/Ardian
Robert Whitbourn
Nothing to Disclose
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Abstract
•
•
•
•
Background: Catheter-based renal artery denervation (RDN) has been shown to significantly
lower blood pressure (BP) in certain patients with uncontrolled hypertension. Patients with
isolated systolic hypertension (ISH; systolic BP [SBP] ≥140 mm Hg and diastolic BP<90 mmHg)
are at higher risk for stroke and coronary events.
Methods: Pooled data from denervated patients in SYMPLICITY HTN-3 and the Global
SYMPLICITY Registry were used to compare baseline characteristics and SBP change at 6
months between patients with ISH and those with combined systo-diastolic hypertension
(CH).
Results: A total of 538 patients had ISH and 793 patients had CH. Patients with ISH were
significantly older than those with CH (65 years vs 55 years), had more type 2 diabetes
mellitus (52.4% vs 34.3%) and a lower estimated glomerular filtration rate (71.3 vs 78.6
ml/min/1.73m2); all p<0.001. Baseline office and 24-hour ambulatory BP was 166/78 ± 16/8
mmHg and 152/77 ± 15/10 mmHg, respectively for the ISH group and 177/104 ± 20/12
mmHg and 161/95 ± 17/12 mmHg, respectively for the CH group. Both the office and
ambulatory BP changes were significantly less pronounced in ISH compared with CH, even
when adjusted for differences in baseline SBP.
Conclusions: Patients with ISH and CH appear to exhibit a reduction in SBP after RDN but this
effect seems less pronounced in the ISH group
For OMA distribution only. Trademarks may be registered and are the property of their respective owners © 2015 Medtronic, Inc. All Rights Reserved. 10188475DOC_1A 3/15
Background
• Catheter-based renal artery denervation (RDN) has been shown to
significantly lower blood pressure (BP) in certain patients with
uncontrolled hypertension. However, information on the treatment effect
in different types of hypertension is largely unknown.
• Patients with isolated systolic hypertension (ISH; systolic BP [SBP] ≥140
mm Hg and diastolic BP<90 mm Hg) are at higher risk for stroke and
coronary events.
• A recent study comparing the effect of RDN in patients with ISH and
patients with combined systo-diastolic hypertension (CH), indicated that
the magnitude of office and ambulatory BP reduction was less
pronounced in the patients with ISH.1
• The current analysis aims to further evaluate the BP-lowering effect of
RDN in patients with ISH compared to patients with CH, using data from
the SYMPLICITY HTN-3 and Global SYMPLICITY Registry (GSR) studies.
1
Ewen, S et al. Hypertension. Online ahead of print October 20, 2014. doi:10.1161/HYPERTENSIONAHA.114.04336.
For OMA distribution only. Trademarks may be registered and are the property of their respective owners © 2015 Medtronic, Inc. All Rights Reserved. 10188475DOC_1A 3/15
Methods
•
•
For this post-hoc analysis, all patients from the SYMPLICITY HTN-3 Study were
pooled with the patients from GSR who had a baseline office-based SBP ≥140 mm
Hg while receiving at least 3 antihypertensive medications of different classes.
Patients were stratified into 2 groups:
– The ISH group included all patients with a baseline office SBP ≥140 mm Hg and office
DBP <90 mm Hg.
– The CH group included all patients with a baseline office SBP ≥140 mm Hg and office
DBP ≥90 mm Hg.
•
Trial
ISH
CH
HTN-3
147
318
GSR (OSBP>140 mm Hg)
391
475
Total
538
793
Changes in BP levels at 6 months relative to baseline by office BP and ambulatory
BP measurements (ABPM) were compared between the ISH and CH groups.
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Results
Patient Baseline Characteristics
CH
ISH
N=793
N=538
Age, years
55.38 ± 11.03
65.40 ± 10.04
< 0.001
Male sex
62.4
59.5
0.302
31.9 ± 6.6
30.9 ± 6.6
0.009
History of diabetes mellitus, type 2
34.3
52.4
< 0.001
History of coronary artery disease
11.3
13.8
0.173
History of obstructive sleep apnea
20.3
13.8
0.003
History of stroke
10.7
5.4
0.081
eGFR, ml/min/1.73m2
78.6 ± 21.9
71.3 ± 22.9
< 0.001
Heart Rate, bpm
73.2 ± 14.1
65.1 ± 11.1
< 0.001
Pulse Pressure
74.7 ± 17.9
87.7 ± 17.1
<0.001
Office systolic blood pressure
178.8 ± 20.0
165.8 ± 16.1
< 0.001
Office diastolic blood pressure
104.0 ± 11.6
78.1 ± 8.1
< 0.001
24-hour systolic blood pressure
160.8 ± 16.7
152.5 ± 15.5
< 0.001
24-hour diastolic blood pressure
95.0 ± 12.1
77.4 ± 10.3
< 0.001
% or mean ± SD
BMI, kg/m2
P-value
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Antihypertensive Medications at Baseline
CH
(n=783)
ISH
(n=535)
P-value
4.62 ± 1.36
4.64 ± 1.19
0.80
ACE inhibitors
37.7
39.1
0.64
Angiotensin receptor blockers
61.0
63.9
0.30
Calcium channel blockers
74.5
76.1
0.52
Diuretics
86.3
86.7
0.87
Aldosterone antagonists
24.6
17.4
0.002
Alpha 2 Agonist
38.3
39.8
0.61
Direct renin inhibitors
9.1
5.6
0.02
Beta blockers
81.5
81.5
1.00
Alpha-adrenergic blocker
22.7
32.1
< 0.001
Direct-acting vasodilators
25.2
20.4
0.046
% or mean ± SD
No. of anti-hypertensive medication classes
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Office Systolic BP Change at 6 Months
HTN-3
Change in blood pressure (mm Hg)
0
RDN
n=225
Sham
n=125
n=121
n=48
-5
-10
-9.2 ± 24.5
-10.7± 22.6
-12.1 ± 27.2
CH
ISH
-15
-20
-2.92 (-11.83, 6.00)
P=0.52
-17.9 ± 24.3
-7.21 (-12.42, -2.01)
P=0.007
-25
P-values are unadjusted
BL SBP
Age
Heart rate
182
175
182
174
54
65
52
66
73.8
63.6
75.3
63.5
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Office Systolic BP Change at 6 Months
GSR
Change in blood pressure (mm Hg)
0
n=379
n=304
-5
-10
-10.7± 22.6
-15
-20
CH
-19.2 ± 23.6
-8.48 (-11.84, -5.13)
P<0.001
-25
ISH
P-value is unadjusted
BL SBP
176
162
Age
56
65
Heart rate
73.0
65.8
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Office Systolic BP Change at 6 Months
Pooled Dataset
0
n=680
n=445
Change in blood pressure (mm Hg)
-5
-10
-10.8
-15
-18.7
-20
CH
-8.0 [-10.6, -5.3]
P<0.001
Adjusted P=0.031
-25
BL SBP
176
162
Age
56
65
Heart rate
73.0
65.8
ISH
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Ambulatory Systolic BP Change at 6 Months
Pooled Dataset
Change in blood pressure (mm Hg)
0
n=467
n=293
-5
-5.2
-10
-9.2
-4.1 (-6.3, -1.7)
-15
P<0.001
Adjusted P=0.013
-20
CH
-25
ISH
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Conclusions
• Both patients with CH as well as ISH appear to exhibit a
reduction in systolic BP after RDN, however this BP-lowering
effect seems less pronounced in the ISH group.
For OMA distribution only. Trademarks may be registered and are the property of their respective owners © 2015 Medtronic, Inc. All Rights Reserved. 10188475DOC_1A 3/15