1. New Frontiers in Devices to Treat Refractory Hypertension
Scope of the Problem: the Pharm Approach
John Somberg, M.D.

2. U.S. Hypertension Statistics
76,400,000 U.S. Population Hypertensive
(equally distributed between men & women)
33.5% of adults > 20 years have hypertension
(NHANES )
African American adults 44% hypertensive
Among hypertensive adults
80% aware of their condition
71% are using antihypertensive medication
48% aware of being hypertensive controlled with meds
Resistant hypertension (BP > 140/90 on BP meds 3 different
categories)
8-9% of population
Estimated cost (direct & indirect 2008) billion (NHLBI)

4. Hypertension Treatment & Control in
Europe, Canada & U.S.
Prevalence of age-adjusted hypertension (140/90) age 35-64
U.S. 28%
Canada 27%
Sweden 38%
Italy 38%
England 42%
Spain 47%
Germany 55%

6. Drugs to Treat Hypertension
Class Toxicity
Diuretics hypokalemia
↑ lipids
fatigue
Centrally Acting
methyldopa CNS – sedation
clonidine rebound
quanfacine
Ganglion-blocking
guanethine OH
reserpine sympathoplegia
depression
Beta-blockers bronchial constriction
bradycardia
Alpha-blockers
prazosin, terazosin, doxazosin 1st dose
CNS
tachycardia
Vasodilators
hydralazine CNS, tachycardia
minoxidil hypertrichosis
fenolapam
Ca++ Blockers peripheral edemia
constipation
ACE Inhibitors cough
angioedemia
hyperkalemia
renal failure
ARBs angioedemia
Renin Inhibitors hyperkalemia
aliskiren renal impairment

7. Downsides of Chronic Pharmacologic Therapy
Toxicity
Cost
Tolerance
Drug Interactions

8. Resistant Hypertension
BP > 140/90 mmHg
Using antihypertensive from 3 different drug classes
or drugs from > 4 antihypertensive drug classes
regardless of BP
This represents 12.8% of population taking
antihypertensive therapy
(NHWES )

9. Resistant Hypertension & Medication
53% of NHANES surveyed patients were controlled at <140/90 BP
Framingham only 48% of treated participants were controlled at 140/90 & less than 40% of elderly participants (>75 year) were controlled
NHAMES surveyed patients with chronic kidney disease, only 37% were controlled to <130/80 and only 25% of patients with diabetes were controlled at <130/85
ALLHAT after 5 years
34% remained uncontrolled on average of 2 meds
50% on 3 meds for control
16% not controlled
AASK study an average of 3 agents was needed to achieve a mean arterial BP goal of <95 mmHg.

10. Pharmacologic Causes of Hypertension
Glucocorticoids
Mineralcorticoids
Licorice, carbenoxolone, fluoroprednisolone, ketoconazol
Sex hormones
Estrogen, progesterone, androgens, danazol
Sympathomametics
phenylephrine, dipiralyl, phenylpropanolamine, pseudoephedrine,
caffine, deongestants (oxymetazoline), ephedra, cocaine,
methylphenidate, siburtamine, clozapine, venlafaxine, selegiline,
tricyclics, buspirone, fluoxetine, thioridazine, disulfiram
Renin angiotensin activation
lead, torcetrapid
Vasoconstrictors
cyclosporine A
tacrolimus
Volume load
NSAID’s
erythropoietin
alcohol, bevacizumab, sorafenib
Unknown Mechanisms
acetaminophen, scopolamine, naloxone, metoclopramide, alizapride,
prochlorperazine, lithium, paclitaxel, cadmium, arsenic,
bromocriptine, amphotericine B

11. New Pharmacologic Therapy
Aliskiren added to an ACE (or ARB) and a ß blocker can be effective in hypertension
DORADO trial suggests that ET-a receptor antagonist darusentan is effective in refractory hypertension
Cicletanine – more natriuresis and less kaliuresis and effective new thiazide diuretic

12. Nonpharmacologic Therapy of Hypertension
Are there safe, cost-effective nonpharmacologic
therapies for the treatment of drug resistant
hypertension?
If nonpharmacologic therapies are safe and cost
effective in treating resistant hypertension, can they
be considered for nonresistant hypertension?