1. SALES TRAINING ONLY.

2. • Introduction to Module Series
• Module 1 - Resistant hypertension: Definitions and prevalence
• Module 2 - Renal sympathetic activity in metabolic diseases
• Module 3 - Differential diagnosis of resistant hypertension
• Module 4 - Conventional management of resistant hypertension
• Module 5 - Preclinical and early clinical rationale for renal denervation
• Module 6 - Renal denervation: The procedure
• Module 7 - Renal denervation: Clinical trial data
• Module 8 - Patient selection
SALES TRAINING ONLY.

3. Resistant Hypertension:
The Clinical Issue
Globally, <50% of treated hypertensives achieve BP goal
Patients With Controlled BP (%)
53.1
49.5
41.0
33.6
29.2 28.8
15.5
Kearney PM et al. J Hypertens. 2004;22:11-19.
SALES TRAINING ONLY.

4. The Role of the Sympathetic Nervous
System (SNS) in Resistant Hypertension
Renal sympathetic nerves contribute to development and
perpetuation of hypertension
• Sympathetic outflow to kidneys is activated in patients with
essential hypertension1
• Efferent sympathetic outflow:2
– Stimulates renin release
– Increases tubular sodium reabsorption
– Reduces renal blood flow
• Afferent signals from kidney modulate central sympathetic
outflow and directly contribute to neurogenic hypertension3-5
1. Esler M et al. Hypertension. 1988;11:3–20; 2.DiBona GF, Kopp UC. Physiol Rev. 1997;77:75–197; 3. Kopp UC et al. Am J
Physiol Regul Integr Comp Physiol. 2007;293:R1561–R1572; 4. Hausberg M et al. Circulation. 2002;106:1974–1979; 5.
Stella A, Zanchetti A. Physiol Rev. 1991;71: 659–682.
SALES TRAINING ONLY.

5. • Introduction to Module Series
• Module 1 - Resistant hypertension: Definitions and prevalence
• Module 2 - Renal sympathetic activity in metabolic diseases
• Module 3 - Differential diagnosis of resistant hypertension
• Module 4 - Conventional management of resistant hypertension
• Module 5 - Preclinical and early clinical rationale for renal denervation
• Module 6 - Renal denervation: The procedure
• Module 7 - Renal denervation: Clinical trial data
• Module 8 - Patient selection
SALES TRAINING ONLY.

6. Learning Objectives
By the end of the module, you should be
able to:
• Recognize the differences between
uncontrolled hypertension and
resistant hypertension
• Define treatment-resistant
hypertension and recognize how the
definition varies according to the
AHA, BHS, ESH and JNC VII
Guidelines
• Identify the typical patient features of
resistant hypertension and how these
features relate to patients with white-
coat syndrome
SALES TRAINING ONLY.

7. Renal Sympathetic Denervation
A potential treatment option for selected patients with resistant hypertension
• Nonselective surgical sympathectomy was historically used to treat
hypertension prior to advent of antihypertensive drugs1
• New endovascular catheter technology enables selective renal
denervation
• First-in-man trial demonstrated reduction in sympathetic activity and
renin release with reductions in central sympathetic outflow2
• Pivotal multicenter trial demonstrates procedure is safe and effective
in providing significant BP reductions in treatment-resistant
hypertensive patients3
1. Hoobler SW et al. Circulation. 1951;4:173-183;
2. Schlaich MP et al. N Engl J Med. 2009;361:932-934; 3. Symplicity HTN-2 Investigators. Lancet. 2010;376:1903-1909.
SALES TRAINING ONLY.

8. Definitions of Resistant Hypertension Vary
United States Europe
JNC 7 (2003)1 AHA (2008)2 ESH (2007)3 BHS (2011)4
Failure to reach BP BP that remains BP ≥140/90 mm Hg Someone whose
goal in patients who above goal despite despite treatment BP is not
are adhering to full concurrent use of with at least 3 controlled to
doses of an 3 antihypertensive drugs (including a <140/90 mm Hg,
appropriate 3-drug agents of different diuretic) in adequate despite optimal or
regimen that classes (ideally, doses and after best-tolerated
includes a diuretic one of which is a exclusion of doses of third-line
diuretic, and all spurious treatment
agents are hypertension such
optimized) as isolated office
hypertension and
failure to use large
cuffs on large arms
AHA=American Heart Association; BHS=British Hypertension Society; ESH=European Society of Hypertension; JNC=Joint National Committee
1. Chobanian AV et al. JAMA. 2003;289:2560-2572; 2. Calhoun DA et al. Circulation. 2008;117:e510-526; 3. Mancia G et al. J Hypertens.
2007;25:1751-1762; 4. National Clinical Guideline Centre. Available at: http://www.nice.org.uk/nicemedia/live/12167/54727/54727.pdf.
Accessed Nov 19 2011.
SALES TRAINING ONLY.

9. Not All Refractory Hypertension is
True Treatment-Resistant Hypertension
 Not all patients who fail to respond to antihypertensive therapy have true
treatment-resistant hypertension
 Long-term outcomes vary substantially among the various subtypes of
refractory hypertension
 Optimal treatment modalities and approach to management vary among subtypes
Secondary Pseudoresistance1,2 Masked White coat True treatment-
Hypertension1 Hypertension2 hypertension2 resistant
hypertension*3
Hypertension Apparent Clinic BP <140/90 Clinic BP ≥140 or BP ≥140/90 mm Hg
elicited or hypertension due to mm Hg; daytime ≥90 mm Hg; despite adequate
exacerbated by lack of adherence, BP >135 or >85 daytime BP doses of ≥3 drugs
other drugs or poor BP mm Hg <135/85 mm Hg (including diuretic)
diseases measurement after exclusion of
technique spurious
hypertension
*European Society of Hypertension definition
BP=blood pressure.
1. Calhoun DA et al. Circulation. 2008;117:e510-526; 2. Pierdomenico SD et al. Am J
Hypertens. 2005;18:1422-1428; 3. Mancia G et al. J Hypertens. 2007;25:1751-1762. SALES TRAINING ONLY.

10. Typical Features of Patients With Resistant
Hypertension vs White-Coat Hypertension
• Compared with patients with white-coat hypertension, true
resistant hypertension is associated with:
– Male gender
– Longer duration of hypertension
– Smoking
– Diabetes
– Target-organ damage (as measured by presence of
LVH, impaired renal function, microalbuminuria)
– Documented CVD
• All of these associations are weak
– Demographics have a low discriminating value for the
diagnosis of resistant hypertension
– ABPM is desirable for correct diagnosis and management
ABPM=ambulatory blood pressure measurement; CVD=cardiovascular disease; LVH=left ventricular hypertrophy.
de la Sierra A et al. Hypertension. 2011;57:898-902.
SALES TRAINING ONLY.

11. When Stringent Definitions are Used, 7.6% to
18% of Patients Have True Treatment-Resistant
Hypertension
• Spanish ABPM Monitoring Registry definition:1
– Use of 3 antihypertensive drugs 18%
(with 1 diuretic)
– Clinic BP ≥140 and/or ≥90 mm Hg
– Daytime BP ≥130 and/or ≥80 mm Hg
• Pierdomenico et al definition:2
– Use of triple therapy
Patients (%)
– Clinic BP ≥140 or ≥90 mm Hg
at ≥2 visits
– Daytime BP ≥135 or ≥85 mm Hg
• Both studies excluded patients at BP 7.6%
target being treated with ≥4 drugs1,2
– True prevalence of treatment-resistant hypertension
may therefore be somewhat higher
Spanish ABPM Italy: Pierdomenico
Monitoring Registry1 et al2
(N=8295) (N=742)
ABPM=ambulatory blood pressure monitoring; BP=blood pressure.
1. de la Sierra A et al. Hypertension. 2011;57:898-902;
2. Pierdomenico SD et al. Am J Hypertens. 2005;18:1422-1428.
SALES TRAINING ONLY.

12. Summary
• Uncontrolled hypertension is not synonymous with resistant
hypertension
– Resistant hypertension may be broadly defined as BP that remains
above goal despite full doses of ≥3 antihypertensive medications
– Resistant hypertension includes patients who achieve BP control but
require ≥4 antihypertensive agents
• In epidemiologic studies, rates of treatment-resistant hypertension
vary from 7.6% (Spain) to 28.0% (US)
• A number of “typical features” have been identified for patients with
resistant hypertension, but associations are weak
– ABPM is desirable for correct diagnosis and management
ABPM=ambulatory blood pressure monitoring
SALES TRAINING ONLY.