intervention in hypertension with Simplicity Trial

1. INTERVENTIONS IN
HYPERTENSION

2. • Hypertension is defined as a usual office blood
pressure of 140/90 mm Hg or higher

4. RESISTANT HYPERTENSION
• refers to patients with blood pressures
persistently >140/90 mmHg despite taking
three or more antihypertensive agents,
including a diuretic, in a reasonable
combination and at full doses

5. RENAL DENERVATION
• overactivity of the sympathetic nervous
system contributes to hypertension,especially
severe drug-resistant hypertension.
• The targets of RDN are both the efferent
postganglionic renal sympathetic nerves and
the renal sensory (afferent) nerves

7. Hypertrophy
Arrhythmia
Oxygen Consumption
Vasoconstriction
Atherosclerosis
Insulin
Resistance
Renal Sympathetic Activation: Afferent Nerves
Kidney as Origin of Central Sympathetic Drive
Renal Afferent
Nerves
↑ Renin Release  RAAS activation
↑ Sodium Retention
↓ Renal Blood Flow
Sleep
Disturbances
7

10. • 8-F femoral artery access, an 8-F guide catheter
was positioned in the renal arteries, allowing
delivery of a radiofrequency catheter into the
renal arteries and circumferential application of
radiofrequency energy
• The catheter tip is steerable via a hand control
and is connected to a console
• Delivery of radiofrequency energy was monitored
with a temperature and impedance sensor at the
tip of the catheter such that unwanted tissue
injury related to overheating was avoided

12. Lancet. 2010;376:1903-1909.

13. The simplicity HTN-2 Trial
• Purpose: To demonstrate the effectiveness of catheter-based
renal denervation for reducing blood pressure in patients with
uncontrolled hypertension.
• Study design: Randomized, controlled clinical trial.
• Patients: 106 patients randomized 1:1 to treatment with
renal denervation vs. control.
• Participating centres: 24 centers in Europe, Australia, & New
Zealand.

14. The simplicity HTN-2 Trial
Inclusion Criteria:
-Office SBP ≥ 160 mmHg (≥ 150 mmHg with type II diabetes
mellitus)
-3+ more anti-HTN medications
-Age 18-85 years
Exclusion Criteria:
-Significant renal artery abnormalities or prior renal artery
intervention
-eGFR < 45 mL/min/1.73m2 -Type 1 diabetes
-Contraindication to MRI
-Significant stenotic valvular heart disease
-MI, unstable angina, or CVA in the preceding 6 months

15. Before randomisation and to assess eligibility:
• Screening process required patients to
record daily bd automated BP
measurements and to document drug
compliance
• Renal artery anatomical screening, with
renal duplex, CT, MRI or renal angiography to
confirm anatomical eligibility.
• Baseline creatinine, Cystatin
• 24hr BP measurement.

19. Follow up
• At 1, 3 and 6 months, with rpt creat, Cystatin C, BP
• Office and home BP readings, average of 3.
• Daily home BP and drug compliance prior to the 6 month FU.
• At 6 months: 24hr BP monitor and renal imaging in the renal
denervation group.

20. . 84% of RDN patients had ≥10 mmHg reduction in SBP
. 10% of RDN patients had no reduction in SBP
. p <0.001 for difference between RDN and Control

26. Adverse events
• No significant change in renal function.
• One renal artery dissection from injection of contrast into renal artery
wall during dye angiography.
• The lesion was stented without further consequences.
Minor adverse events (n=52)
•1 femoral artery pseudoaneurysm  manual compression
•1 post-procedural drop in BP resulting in a reduction in medication
•1 urinary tract infection
•1 prolonged hospitalization for evaluation of paraesthesias
•1 back pain treated with pain medications & resolved after one month
6-month renal imaging (n=43)
•No vascular abnormality at any RF treatment site
•1 MRA indicates possible progression of a pre-existing stenosis unrelated to RF
treatment (no further therapy)

27. Conclusions
• Catheter-based renal denervation, done in a multicentre,
randomised trial in patients with treatment-resistant
essential hypertension, resulted in significant reductions in
BP.
• The technique was applied without major complications.
• This therapeutic innovation, based on the described neural
pathophysiology of essential hypertension, affirms the
crucial relevance of renal nerves in the maintenance of BP
in patients with hypertension.
• Catheter-based renal denervation may be beneficial for
patients with treatment-resistant essential hypertension.

28. Limitations
• Non-blinded trial.
• ?long-term benefit, ?evidence of reinnervation
• Small number of patients.
• Was the population truly treatment resistant?
• Adjustments in medications, unclear effect on pill
burden
• Effect in patients with severe CKD.

30. • SYMPLICITY HTN-3 is the first prospective,
multi-center, randomized, blinded, sham
controlled study to evaluate both the safety
and efficacy of percutaneous renal artery
denervation in patients with severe
treatment-resistant hypertension.
• The trial included 535 patients enrolled by 88
participating US centers.

31. • The primary efficacy end point was the mean
change in office systolic blood pressure from
baseline to 6 months in the denervation
group, as compared with the mean change in
the sham control group, with a superiority
margin of 5 mm Hg
• a secondary efficacy end point was the change
in mean 24-hour ambulatory systolic blood
pressure

32. • The primary safety end point was a composite
of major adverse events, defined as death
from any cause, endstage renal disease, an
embolic event resulting in end-organ damage,
renal-artery or other vascular complications,
or hypertensive crisis within 30 days or new
renal-artery stenosis of more than 70% within
6 months.

33. Key Inclusion Criteria
• Age ≥18 and ≤80 years at time of randomization
• Stable medication regimen including full tolerated doses of 3 or
more antihypertensive medications of different classes,
including a diuretic (with no changes for a minimum of 2 weeks
prior to screening) and no expected changes for at least 6
months
• Office SBP ≥160 mm Hg based on an average of 3 blood pressure
readings measured at both an initial and a confirmatory
screening visit
• Written informed consent

34. Key Exclusion Criteria
• ABPM 24 hour average SBP <135 mm Hg
• eGFR of <45 mL/min/1.73 m2
• Main renal arteries <4 mm diameter or <20 mm
treatable length
• Multiple renal arteries where the main renal artery is
estimated to supply <75% of the kidney
• Renal artery stenosis >50% or aneurysm in either renal
artery
• History of prior renal artery intervention

41. • This blinded trial did not show a significant
reduction of systolic blood pressure in patients
with resistant hypertension 6 months after
renal-artery denervation as compared with a
sham control.