SLIDE 1 Het einde van therapieresistente hypertensie in zicht?
Wilko Spiering
- Afd. Vasculaire Geneeskunde
Symposium Vasculaire Geneeskunde - NVIVG 2020, 11 september 2020
SLIDE 2 Disclosures
- Research contract: none
- Consulting: Vascular Dynamics
- Other: none
SLIDE 3 Hypertension control has plateaued
NCD Risk Factor Collaboration (NCD-RisC), Lancet 2019
SLIDE 4 Definition resistant hypertension (ESC/ESH 2018)
- ‘Resistant to treatment when the recommended treatment
strategy fails to lower office SBP and DBP values to <140 mmHg and/or <90 mmHg, respectively, and the inadequate control of BP is confirmed by ABPM or HBPM in patients whose adherence to therapy has been confirmed’
- Recommended treatment strategy should include:
– appropriate lifestyle measures – optimal or best-tolerated doses of three or more drugs, which should include a diuretic, typically an ACE inhibitor
Williams, Eur Heart J 2018
SLIDE 5 Increased risk in apparent resistant hypertension
Groenland, submitted for publication
SLIDE 6
Work-up in resistant hypertension
1. Exclude pseudoresistant hypertension 2. Reverse contributing factors 3. Screen for secondary hypertension 4. Optimize pharmacotherapy 5. Consider device-based therapy
SLIDE 7 Work-up in resistant hypertension
- 1. Exclude pseudoresistant hypertension
2. Reverse contributing factors 3. Screen for secondary hypertension 4. Optimize pharmacotherapy 5. Consider device-based therapy
SLIDE 8 Causes of pseudoresistant hypertension
- Inaccurate BP measurement
- White coat hypertension
- Suboptimal antihypertensive therapy
- Poor adherence to lifestyle aspects
- Poor adherence to antihypertensive therapy
SLIDE 9 Nonadherence in resistant hypertension
Jung, J Hypertens 2013
SLIDE 10 Nonadherence in hypertension
- ~50% nonadherent to prescribed medication
- 15-20% completely nonadherent to prescribed medication
- Determinants of nonadherence:
– Younger age – Female sex – # of antihypertensive drugs prescribed – Total pill burden – Prescription of CCB
Gupta, Hypertension 2017 Lawson, J Hypertens 2020
SLIDE 11
LC-MS/MS to measure adherence
SLIDE 12 Analysis for adherence in UMC Utrecht
- Liquid chromatography-tandem mass spectrometry (LC-
MS/MS)
- Only 100 μL plasma
- Detects 34 antihypertensives in single run
- Validated for Lower Limit of Quantification (LLOQ)
- Measured in all new referred patients for difficult-to-
control hypertension
Punt, J Chromatogr B Analyt Technol Biomed Life Sci 2019
SLIDE 13 Adherence in true refractory hypertension
, despite:
– Effective doses of ≥5 different classes – Including long-acting thiazide-like diuretic – Including mineralocorticoid antagonist
Siddiqui, Hypertension 2020
SLIDE 14 Adherence in true refractory hypertension
Siddiqui, Hypertension 2020
Unattended AOBP ≥130/80 Mean 24hr ABPM ≥125/75 and mean awake ≥130/80
SLIDE 15 Adherence in true refractory hypertension
Siddiqui, Hypertension 2020
- Adherence ~50%
- Prevalence true refractory hypertension is rare
SLIDE 16 Screening for adherence lowers BP
Gupta, Hypertension 2017
SLIDE 17 Work-up in resistant hypertension
1. Exclude pseudoresistant hypertension
- 2. Reverse contributing factors
3. Screen for secondary hypertension 4. Optimize pharmacotherapy 5. Consider device-based therapy
SLIDE 18
Contributing factors in resistant hypertension
Resistant hypertension
SLIDE 19 Sodium reduction in resistant hypertension
Pimenta, Hypertension 2009
SLIDE 20 Work-up in resistant hypertension
1. Exclude pseudoresistant hypertension 2. Reverse contributing factors
- 3. Screen for secondary hypertension
4. Optimize pharmacotherapy 5. Consider device-based therapy
SLIDE 21
Secondary causes of resistant hypertension
SLIDE 22 Work-up in resistant hypertension
1. Exclude pseudoresistant hypertension 2. Reverse contributing factors 3. Screen for secondary hypertension
- 4. Optimize pharmacotherapy
5. Consider device-based therapy
SLIDE 23 Optimize pharmacotherapy
- Withdrawal interfering medications
- Diuretic therapy:
– Higher doses – Long-acting thiazide-like in stead of hydrochlorothiazide – Loop diuretics when eGFR <30 ml/min/1.73m2
– Low dose combination vs. maximal uptitration – Triple FDC vs. dual FDC
- Mineralocorticoid receptor antagonists
SLIDE 24 Core drug treatment strategy
Williams, Eur Heart J 2018
SLIDE 25 PATHWAY-2 trial
Williams, Lancet 2015
SLIDE 26 Work-up in resistant hypertension
1. Exclude pseudoresistant hypertension 2. Reverse contributing factors 3. Screen for secondary hypertension 4. Optimize pharmacotherapy
- 5. Consider device-based therapy
SLIDE 27 Device-based therapy of hypertension
- Renal denervation
- Baroreflex amplification
- Iliac AV anastomosis
- Carotid body ablation
- Deep brain stimulation
- Transcutaneous median nerve stimulation
- Cardiac neuromodulation therapy
SLIDE 28 Device-based therapy of hypertension
- Renal denervation
- Baroreflex amplification
SLIDE 29
SLIDE 30 Renal denervation
- Radiofrequency-based renal denervation
- Ultrasound-based renal denervation
- Alcohol-mediated renal denervation
SLIDE 31 Symplicity HTN-1
Krum, Lancet 2009
SLIDE 32 Symplicity HTN-2
Esler, Lancet 2010
SLIDE 33 Symplicity HTN-3
Bhatt, N Engl J Med 2014
SLIDE 34
Symplicity vs. Spyral catheter
SLIDE 35 SPYRAL HTN-OFF MED
Böhm, Lancet 2020
SLIDE 36 SPYRAL HTN-ON MED
Kandzari, Lancet 2018
SLIDE 37
Where are the renal nerves?
SLIDE 38 Ultrasound - Paradise system
- Cool – protect the renal artery
from the inside
- Heat – ablate the renal nerves on
the outside
Ultrasonic Heating + Water Cooling Paradise Thermal Profile
SLIDE 39 RADIANCE-HTN SOLO
Azizi, Lancet 2018
SLIDE 40 Meta-analysis sham-controlled RCTs in RDN
Sardar, J Am Coll Cardiol 2019
SLIDE 41
Alcohol - Peregrine system
SLIDE 42 Device-based therapy of hypertension
- Renal denervation
- Baroreflex amplification
SLIDE 43 Baroreflex amplification
- Baroreflex activation therapy (‘electrical’)
- Endovascular baroreflex amplification (‘stent’)
- Selective vagal nerve stimulation
SLIDE 44 Baroreflex in blood pressure control
From: La Rovere, Vasc Pharmacol 2015
SLIDE 45
Baroreflex Activation Therapy (BAT)
SLIDE 46
Mechanism of action
SLIDE 47 Rheos pivotal trial
– Acute SBP responder rate at 6 months – Sustained responder rate at 12 months
– Procedure safety – BAT safety – Device safety
SLIDE 48
SLIDE 49
SLIDE 50
SLIDE 51 Barostim neo ongoing clinical trials
Study n Design Primary outcome Completion date ESTIM-rHTN, NCT02364310 128 Randomized,
(PROBE) 24-hr daytime SBP, incremental cost- effectiveness ratio at 12 months Q1 2021 Nordic BAT, NCT02572024 100 Randomized, double blind 24-hr SBP at 16 months ??
SLIDE 52 EndoVascular Baroreflex Amplification (EVBA)
implant
- Reshapes the carotid sinus
to ‘square the circle’
without over-expansion
- Increases stretch amplifying
baroreceptor signals to CNS MobiusHD
SLIDE 53 Change in blood pressure
Spiering, Lancet 2017
Office blood pressure Ambulatory blood pressure
SLIDE 54 Longterm effects in BP lowering
van Kleef, submitted 2020
SLIDE 55 Selective vagal nerve stimulation
Plachta, J Neural Eng 2014
SLIDE 56 Endothelin receptor antagonist: aprocitentan
Trensz, J Pharmacol Exp Ther 2019
SLIDE 57 Angiotensinogen siRNA
Uijl, Hypertension 2019
SLIDE 58
Digital health feedback system
SLIDE 59 Take home messages
- True resistant hypertension is probably rare
- ‘It is the adherence, stupid!’
- Innovative antihypertensive treatments are needed more
than ever
SLIDE 60
