Resistant hypertension

RESISTANT HYPERTENSION
Dr-Rashna Sharmin Juthi
MBBS
Eastern Medical College and Hospital

“AS WE ENTER THE THIRD MILLENNIUM,
WE ARE ON THE VERGE OF THE
BIGGEST EPIDEMIC OF CARDIOVASCULAR
DISEASE IN HUMAN HISTORY,
MOST OF IT BLOOD PRESSURE RELATED”
DR. VINOD SHARMA
NATIONAL HEART INSTITUDE
NEW DELHI

DEFINITION
2008 AMERICAN HEART ASSOCIATION GUIDELINE
 BLOOD PRESSURE THAT REMAINS ABOVE GOAL
IN SPITE OF CONCURRENT USE OF THREE
ANTIHYPERTENSIVE AGENTS OF DIFFERENT
CLASSES, ONE OF WHICH SHOULD BE A DIURETIC.
PATIENTS WHOSE BLOOD PRESSURE IS
CONTROLLED WITH FOUR OR MORE MEDICATIONS
ARE CONSIDERED TO HAVE RESISTANT
HYPERTENSION (20-30%).
American Heart Association guideline

PROBLEMS OF RESISTANT HYPERTENSION
Systolic BP difficult
control
Diastolic BP in
old age
• Module of Prof. Dr. Sarma VSN
Rachakonda
• Hon. National Professor of Medicine, IMA – CGP, India
• Senior Consultant Physician & Cardio-metabolic Specialist
• Adjunct Professor, Tamilnadu Dr. MGR Medical University,
Chennai

PREVALENCE
• APPROXIMATELY 25% OF ADULTS WORLDWIDE ARE AFFECTED BY
HYPERTENSION
• HYPERTENSION IS RESPONSIBLE FOR 13% OF TOTAL WORLDWIDE DEATHS.
• RESISTANT HYPERTENSION IS FOUND IN UP TO 10-20% OF PATIENTS WITH
HYPERTENSION
• IT IS ESTIMATED THAT PATIENTS WITH RESISTANT HYPERTENSION ARE
ALMOST 50% MORE LIKELY TO EXPERIENCE AN ADVERSE CARDIOVASCULAR
EVENT COMPARED WITH PATIENTS WITH BLOOD PRESSURE CONTROLLED BY
THREE OR FEWER ANTIHYPERTENSIVE AGENTS
CIRCULATION 2008, ALLAHT, JOURNAL OF AMERICAN BOARD OF FAMILY MEDICINE 2012

In General Population -
Low
In Specialized Clinics -
15%
In Clinical Trials* - 30%
*ALLHAT (Anti-lipid lowering heart attack trial), CONVINCE, LIFE, INSIGHT

ETIOLOGY
1. PRIMARY CAUSES
2. SECONDARY CAUSES
3. FACTORS CONTRIBUTING TO RESISTANT HYPERTENSION
CIRCULATION 2008, JOURNAL OF AMERICAN BOARD OF FAMILY MEDICINE 2012

CAUSES OF RESISTANT HYPERTENSION
Patient Related
High Sodium Intake
Poor adherence to Rx. plan
Intake of Drugs that raise
BP
Lack of Life Style
Adherence
Physician Related
Sub Clinical Volume Over
Load
Inadequate Use of Diuretics
Progressive Renal
Insufficiency
Unsuspected Secondary
Cause
• Module of Prof. Dr. Sarma VSN Rachakonda
Chennai

STRONG ASSOCIATES OF RESISTANT
HYPERTENSION
•AHI >20•BMI >30
•Creat.
>1.5
•HbA1c >
9.0
T2DM CKD
OSAS
(obstructive
sleep
apnea)
LVH
Rachakonda
• Hon. National Professor of Medicine, IMA –
CGP, India
• Senior Consultant Physician & Cardio-
metabolic Specialist
• Adjunct Professor, Tamilnadu Dr. MGR
Medical University, Chennai

SECONDARY AND RESISTANT HYPERTENSION
Hypertension
Resistant
Secondary
Rachakonda
Chennai

THE PRIMARY CAUSES
• OLDER AGE; ESPECIALLY >75 YEARS
• HIGH BASELINE BLOOD PRESSURE AND CHRONICITY OF UNCONTROLLED
HYPERTENSION
• TARGET ORGAN DAMAGE (LEFT VENTRICULAR HYPERTROPHY, CHRONIC
KIDNEY DISEASE)
• DIABETES
• OBESITY
• ATHEROSCLEROTIC VASCULAR DISEASE
• AORTIC STIFFENING
• SEX (WOMEN)
• ETHNICITY (BLACK)
• EXCESSIVE DIETARY SODIUM
Circulation2008, journal of American board of family medicine 2012

SECONDARY CAUSES OF RESISTANT
HYPERTENSION
• PRIMARY HYPERALDOSTERONISM
• RENAL ARTERY STENOSIS
• RENAL PARENCHYMAL DISEASE
• OBSTRUCTIVE SLEEP APNOEA
• PHAEOCHROMOCYTOMA
• THYROID DISEASES
• CUSHING’S SYNDROME
• COARCTATION OF THE AORTA
• INTRACRANIAL TUMOURS

RHTN & OBSTRUCTIVE SLEEP APNOEA
(OSA)
• PREVALENCE – MEN 24%; WOMEN 9% (WISCONSIN SLEEP
COHORT STUDY)
• HIGH PREVALENCE OF RHTN IN OSA (N = 41); 96% MEN, 65%
WOMEN (APNEA – HYPERAPNOEA INDEX > 10)
• MECHANISM
- INCREASED SYMPATHETIC ACTIVITY
- INCREASED ALDOSTERONE LEVELS
- INCREASE IN REACTIVE OXYGEN SPECIES WITH
CONCOMITANT REDUCTIONS IN NITRIC OXIDE
BIOAVAILABILITY

RHTN & ALDOSTERONE
• PREVALENCE OF PRIMARY HYPERALDOSTERONISM IN PATIENTS
WITH RHTN 11 – 20%
LANCET 2008: 371
• COMPARED TO CONN’S SYNDROME, PICTURE OF BIOCHEMICALLY
CONFIRMED PRIMARY HYPERALDOSTERONISM REMAINS DIVERSE:
- SHOWS NEGATIVE IMAGING
- REMAINS IDIOPATHIC
- HYPOKALEMIA IS USUALLY A LATE MANIFESTATION
- NORMOKALEMIA IS QUITE COMMON AMONG THESE
PATIENTS
J. CLIN ENDOCRINOL METAB 2009

RHTN & RENAL ARTERY STENOSIS (RAS)
• RENOVASCULAR DISEASE ( >70% STENOSIS) FOUND IN MORE THAN
20% CASES UNDERGOING CAG
• ROLE OF SUCH LESION IN CAUSATION OF HYPERTENSION IS
UNKNOWN
• > 90% RAS ARE ATHEROSCLEROTIC (ELDERLY MALE), <10% ARE
DUE TO FOOT AND MOUTH DISEASE (FMD) (F<50 YEARS OF AGE)
• LARGE EXPERIENCE WITH BOTH SURGICAL AND ENDOVASCULAR
REVASCULARIZATION INDICATES THAT SOME PATIENTS WITH
RENOVASCULAR HYPERTENSION EXPERIENCED IMPROVED BP
CONTROL ALTHOUGH RANDOMIZED CONTROLLED TRIAL (RCT) IN
GENERAL HAVE NOT SHOWN CONVINCING BENEFIT IN REGARD TO
IMPROVEMENT IN RENAL FUNCTION OR BP CONTROL
Rachakonda
CGP, India

FACTORS CONTRIBUTING TO
LIFESTYLE FACTORS
• OBESITY
• EXCESS ALCOHOL INTAKE
• EXCESS DIETARY SODIUM
• COCAINE AND AMPHETAMINES MISUSE
DRUG RELATED CAUSES
• NON-STEROIDAL ANTI-INFLAMMATORY DRUGS
• CONTRACEPTIVE HORMONES—COMBINED ORAL CONTRACEPTIVES ARE MORE OFTEN
ASSOCIATED
WITH ELEVATED BLOOD PRESSURE, WHEREAS MENOPAUSAL HORMONE THERAPY HAS
MINIMAL EFFECTS ON BLOOD
PRESSURE
PPT ON RESISTANT HYPERTENSION PUBLISHED BY HEALTH CARE
LINK:HTTP://WWW.SLIDESHARE.NET/DRANJALIVYAS/RESISTANT-HYPERTENSION

FACTORS CONTRIBUTING TO RESISTANT
HYPERTENSION (CONT.)
• ADRENAL STEROID HORMONES
• SYMPATHOMIMETIC AGENTS (NASAL DECONGESTANTS, DIET PILLS)
• ERYTHROPOEITIN, CICLOSPORIN, AND TACROLIMUS
• LIQUORICE (SUPPRESSES THE METABOLISM OF CORTISOL)
• HERBAL SUPPLEMENTS (EPHEDRA, BITTER ORANGE, ETC)
VOLUME OVERLOAD
• PROGRESSIVE RENAL INSUFFICIENCY
• HIGH SALT INTAKE
• INADEQUATE DIURETIC THERAPY
PPT on Resistant hypertension published by health care
Link:http://www.slideshare.net/dranjalivyas/resistant-hypertension

DIAGNOSIS
• THE DIAGNOSIS OF RESISTANT HYPERTENSION REQUIRES EXCLUSION OF
BOTH PSEUDO-RESISTANCE AND REVERSIBLE OR ORGANIC CAUSES

PSEUDO-RESISTANCE
• BLOOD PRESSURE CAN BE OVERESTIMATED AS A CONSEQUENCE OF INACCURATE
MEASUREMENT TECHNIQUE
• THE MOST COMMON CAUSES OF OVERESTIMATED BLOOD PRESSURE ARE
USING A CUFF THAT IS TOO SMALL
MEASURING BLOOD PRESSURE BEFORE THE PATIENT IS SITTING QUIETLY
NO ADHERENCE TO PRESCRIBED ANTIHYPERTENSIVE THERAPY

PSEUDO-RESISTANCE
J Am Coll Cardiol 2008;52:1749–57
Causes of Pseudo-Resistant Hypertension

WHITE COAT EFFECT
• MANY PEOPLE HAVE BLOOD PRESSURE IN THE DOCTOR`S OFFICE THAN THEY
HAVE DURING THEIR REGULAR DAY
• IF YOUR DOCTOR SUSPECTS WHITE-COAT EFFECT, YOU MAY NEED TO WEAR A
SMALL, PORTABLE, 24-HOUR PRESSURE MONITOR TO SEE WHAT YOUR PRESSURE
LOOKS LIKE OVER TIME DURING YOUR DAILY ACTIVITES

HOW TO EVALUATE & MANAGE
WITH PATIENTS APPEARING TO
HAVE RESISTANT HYPERTENSION?

INVESTIGATIONS
• UREA AND ELECTROLYTES
• ESTIMATED GLOMERULAR FILTRATION RATE
• PLASMA GLUCOSE
• PLASMA RENIN OR ALDOSTERONE LEVELS
• 24 HOUR URINARY METANEPHRINES OR NOR-METANEPHRINES (FOR
PHAEOCHROMOCYTOMA)
• URINE ANALYSIS—MICRO ALBUMINURIA AND MACRO ALBUMINURIA,
HAEMATURIA)
• ELECTROCARDIOGRAPHY
• ECHOCARDIOGRAPHY SHOULD BE PERFORMED, ALONG WITH
FUNDOSCOPY
• RENAL IMAGING

TARGET ORGAN DAMAGE IN RESISTANT
HYPERTENSION
• LEFT VENTRICULAR HYPERTROPHY
• HYPERTENSIVE RETINOPATHY
• RENAL DISEASE (THAT IS, PERSISTENTLY ELEVATED URINARY ALBUMIN
EXCRETION RATE, HAEMATURIA, OR RENAL IMPAIRMENT)

LIFE STYLE PRINCIPLES FOR
HYPERTENSION
• SALT RESTRICTION
• WEIGHT LOSS
• PHYSICAL ACTIVITY
• SMOKING CESSATION
• ALCOHOL ABSTINENCE
• GLYCAEMIA AND LIPID CONTROL • Module of Prof. Dr. Sarma VSN
Rachakonda
CGP, India

TREATMENTS AVAILABLE FOR RESISTANT
HYPERTENSION
• NON-PHARMACOLOGIC INTERVENTION
• DRUG INTERVENTION
• DEVICE THERAPY

NON-PHARMACOLOGIC INTERVENTION
• WEIGHT LOSS
• REGULAR EXERCISE
• A HIGH FIBER, LOW FAT, LOW SALT DIET
• MODERATION OF ALCOHOL AND CAFFEINE
• CESSATION OR DOWN-TITRATION OF INTERFERING EXOGENOUS SUBSTANCES

DRUG TREATMENT OF RESISTANT
HYPERTENSION
• IF A CORRECTABLE CAUSE IS FOUND, TREAT THAT
• AGGRESSIVE DRUG THERAPY – OPTIMIZING THE CURRENT RX.
• EFFECTIVE DIURESIS – FUROSEMIDE/TORSEMIDE
• MRA ANTAGONISTS, SPIRONOLACTONE, TRIAMTERENE,
AMILORIDE
• HYDRALAZINE OR MINOXIDIL + Β-BLOCKER AND A DIURETIC
• TRANSDERMAL CLONIDINE
johns Hopkins medicine health library

DRUG INTERVENTION
• PATIENTS DEFINED AS HAVING RESISTANT HYPERTENSION WILL ALREADY BE
RECEIVING OR HAVE RECEIVED AT LEAST THREE ANTIHYPERTENSIVE DRUGS THAT IS,
AN ACE INHIBITOR OR ANGIOTENSIN RECEPTOR BLOCKER PLUS A CALCIUM CHANNEL
BLOCKER PLUS A THIAZIDE-TYPE DIURETIC (A+C+D)
• SPIRONOLACTONE (THAT IS, 25 MG ONCE DAILY, INCREASING TO 50 MG ONCE DAILY)
AS THE PREFERRED FOURTH AGENT IF THE BLOOD POTASSIUM CONCENTRATION IS
≤4.5 MMOL/L.
• CENTRALLY ACTING Α AGONISTS (METHYLDOPA AND CLONIDINE) OR DIRECT
VASODILATORS (HYDRALAZINE AND MINOXIDIL) ARE FURTHER OPTIONS.
• THE POTENTIAL ROLES OF OTHER AGENTS SUCH AS ENDOTHELIN RECEPTOR
ANTAGONISTS HAVE YET TO BE CLEARLY DEFINED.
JOHNS HOPKINS MEDICINE HEALTH LIBRARYCirculation2008, journal of American board of family medicine 2012

TREATMENT (CONT.)
DO NOT KEEP ADDING MEDICATIONS
- APPROPRIATE & OPTIMALLY DOSED 3 DRUG REGIMEN
SHOULD SUFFICE FOR BP CONTRO
- ADDING MULTIPLE ADDITIONAL DRUG HAS POTENTIAL
FOR SERIOUS SIDE EFFECTS
- ATTEMPT TO FIND AN UNDERLYING CAUSE & TAILORING
TREATMENT FOR THAT CAUSE IS NECESSARY
circulation 2008

PERFORM A “DIURETIC REVIEW”.
DIURETICS IS THE MAINSTAY OF THE RESISTANT HYPERTENSION
PATIENT MEDICATION REGIMEN & SHOULD BE OPTIMIZED TO SEE
FULL THERAPEUTIC BENEFIT.
circulation 2008

DIURETICS
• STUDIES INDICATE THAT PATIENTS WITH RESISTANT
HYPERTENSION
• FREQUENTLY HAVE INAPPROPRIATE VOLUME EXPANSION
CONTRIBUTING TO THEIR TREATMENT RESISTANCE
SUCH THAT A DIURETIC IS ESSENTIAL TO MAXIMIZE BP
CONTROL
• IN MOST PATIENTS, USE OF A LONG-ACTING THIAZIDE
DIURETIC WILL BE MOST EFFECTIVE
Circulation. 2008;117:e510-e526
circulation 2008

RESISTANT HYPERTENSION – DIURETIC
REVIEW
• THIAZIDE DIURETIC MAY LACK EFFECT AT LOWER GFR (STAGE 3
KIDNEY DISEASE)
• FRUSEMIDE MAY A BETTER OPTION THAN THIAZIDE FOR BP
CONTROL
• BECAUSE OF SHORTER HALF LIFE, FRUSEMIDE MAY BE DOSED
TWICE
circulation 2008

IS PATIENT TAKING BETA-
BLOCKERS?

RESISTANT HYPERTENSION -
BETABLOCKERS
• BETA-BLOCKERS ARE NO LONGER ACCEPTABLE FIRST LINE THERAPIES,
UNLESS THERE ARE COMPELLING INDICATIONS LIKE CAD, CHF ETC. &
• ONE AGENT SPECIFICALLY ATENOLOL MAY INCREASE CENTRAL AORTIC
PRESSURE
CENTRAL STUDY, J CLIN HYPERT 2011
• SWITCH TO A OPTIMAL DOSE OF DUAL ACTING BETA BLOCKER
(CARVEDILOL OR LABETALOL)
- ADDITIONAL LOWERING OF BP DUE TO ∞ BLOCKADE
- BETTER LV / VASCULAR COUPLING
- CARVEDILOL DOES NOT INCREASE INSULIN RESISTANCE
circulation 2008

ALPHA 1-ADRENERGIC RECEPTOR
BLOCKERS
• NOT TO BE USED FOR MONOTHERAPY
• MAY BE USED AS AN ADD-ON FOR RESISTANT
HYPERTENSION
• MAY CAUSE URINARY INCONTINENCE, ESPECIALLY IN
FEMALES, DUE TO BLADDER OUTLET RELAXATION
circulation 2008

•Non-steroidal anti-inflammatory agents
•Sympathomimetics
- Diet pills
- Decongestants
•Stimulants
•Oral contraceptives
•Licorice
•Ephedra
Discontinue or Minimize Interfering Substances
circulation 2008

RHTN – CONSTRUCTING AN EFFECTIVE
ANTIHYPERTENSIVE REGIMEN
THE USE OF LAST LINE AGENTS VIZ.
CLONIDINE LACKS OUTCOME DATA AND
MAY ADD ADVERSE DRUG REACTION &
DECREASED ADHERENCE BECAUSE OF
DOSING FREQUENCY. circulation 2008

RHTN – CONSTRUCTING A POTENT
QUESTION THE VALUE OF HYDRALAZINE
HYDRALAZINE DOES NOT HAVE MUCH
EVIDENCE OF EFFICACY FOR PREVENTION OF
CARDIOVASCULAR BENEFIT WHEN USED FOR
ESSENTIAL HYPERTENSION.
COCHRANE DATABASE SYST REV 2011

RHTN – CONSTRUCTING A POTENT
MINOXIDIL SHOULD BE A LAST RESORT
• POTENT VASODILATOR AND SHOULD BE USED WITH
BETABLOCKER & DIURETICS
• DIFFICULT TO USE & FRAUGHT WITH MANY SERIOUS SIDE
EFFECTS (EDEMA, ANASARCA, PERICARDIAL EFFUSION &
HIRSUTISM)
• CAN BE USED FOR SELECT PATIENTS BY PHYSICIANS WHO ARE
COMFORTABLE WITH DOSING & SIDE EFFECTS
J Hyperten 2007

MINERALOCORTICOID RECEPTOR
ANTAGONISTS (CONT.)
• CONSISTENT WITH REPORTS OF A HIGH PREVALENCE OF
PRIMARY ALDOSTERONISM IN PATIENTS WITH RESISTANT
HT HAVE BEEN STUDIES DEMONSTRATING THAT
• MINERALOCORTICOID RECEPTOR ANTAGONISTS PROVIDE
SIGNIFICANT ANTIHYPERTENSIVE BENEFIT WHEN ADDED
TO EXISTING MULTIDRUG REGIMENS
Circulation. 2008;117:e510-e526

MINERALOCORTICOID RECEPTOR
ANTAGONISTS
• SPIRONOLACTONE
• USED FOR RESISTANT HT WITH NORMAL ALDOSTERONE LEVELS, 12.5-50MG/DAILY
• ADDITIONAL BENEFITS: ANTIPROTEINURIC, IMPROVES HEART FAILURE SURVIVAL
(RALES)
• 10% GYNECOMASTIA
• NOT WHEN CREATININE > 2.5, K > 5.0
circulation 2008

DRUG COMBINATIONS
• CHLORTHALIDONE 25MG + SPIRONOLACTONE 12.5-50 MG
• EXCELLENT DIURETIC MAXIMIZATION, ALSO AGAINST
HYPOKALEMIA
• CHLORTHALIDONE, CAN
• ↓ SERUM K+ ENOUGH TO CAUSE CARDIAC ARREST
• ALDOSTERONE BLOCKERS SPIRONOLACTONE CAN
• PROTECT VULNERABLE PATIENTS AND
• SIGNIFICANTLY REDUCE BP RESISTANT TO ≥ 3 DRUGS,
• A LOGICAL WAY TO PROVIDE MAXIMAL ANTI-HT EFFICACY AND TO
PREVENT HYPOKALEMIA MIGHT BE A
• COMBINATION OF CHLORTHALIDONE AND SPIRONOLACTONE 12.5/25.0
MG/D
Hypertension 2009;54;951-953

RHTN – OPTIMAL ANTIHYPERTENSIVE REGIMEN
PREFERRED ANTIHYPERTENSIVE COMBINATIONS
• A RAAS INHIBITOR & A CALCIUM CHANNEL BLOCKER
• A RAAS INHIBITOR & A DIURETICS (ESPECIALLY A THIAZIDE)
• A RAAS INHIBITOR & A CALCIUM CHANNEL BLOCKER PLUS A
DIURETIC
Eur Heart J: 2011: 32

RHTN – OPTIMAL ANTIHYPERTENSIVE REGIMEN
ACCEPTABLE COMBINATIONS
• BETABLOCKERS & DIURETICS
• CALCIUM CHANNEL BLOCKERS & DIURETICS
• DUAL CALCIUM CHANNEL BLOCKADE (DHP & NDHP AGENT)
Unacceptable Combinations
 Dual RAAS blocker
 RAAS inhibitors plus betablocker
 Betablockers plus anti adrenergic drugs
Eur Heart J 2011

FUTURE OPTIONS FOR RESISTANT
HYPERTENSION
• DIRECT RENIN INHIBITORS
• NEUTRAL ENDOPEPTIDASE (NEP) INHIBITORS
• NEW ALDOSTERONE ANTAGONISTS
• ALDOSTERONE SYNTHASE INHIBITORS
• CLONIDINE EXTENDED RELEASE
• ENDOTHELIN ANTAGONISTS
• NOVEL COMBINATIONS ALGORITHMS
circulation 2008

DEVICE THERAPY
• TWO TECHNIQUES HAVE RECENTLY BEEN EVALUATED:
1. PERCUTANEOUS TRANSLUMINAL RADIOFREQUENCY SYMPATHETIC
DENERVATION OF THE RENAL ARTERIES (RDN)
2. CAROTID BAROREFLEX ACTIVATION

RENAL SYMPATHETIC DENERVATION
• RECENTLY, A CATHETER-BASED APPROACH HAS BEEN DEVELOPED
SELECTIVELY TARGETING THE RENAL SYMPATHETIC NERVES.
• FIVE CE (COUNSEL OF EUROPEAN)-MARKED DEVICES FOR RENAL
SYMPATHETIC DENERVATION ARE AVAILABLE

PROCEDURE OF RENAL SYMPATHETIC
DENERVATION( RDN)
• THE RADIOFREQUENCY CATHETER IS INSERTED PERCUTANEOUSLY VIA THE
FEMORAL ARTERY AND ADVANCED INTO THE RENAL ARTERIES UNDER
FLUOROSCOPY USING A GUIDING CATHETER
• AFTER PLACEMENT, THE CATHETER IS WITHDRAWN FROM DISTAL TO
PROXIMAL SEGMENTS AND FOUR TO EIGHT ABLATIONS ARE ADMINISTERED
WITHIN EACH ARTERY
• FOCALLY APPLIED HEAT (MAXIMUM 70°C) DESTROYS THE SYMPATHETIC
NERVE FIBERS LOCATED IN THE ADVENTITIA
• SIMULTANEOUSLY, THE HIGH RENAL BLOOD FLOW COOLS THE VESSEL WALL
• DUE TO THE CLOSE PROXIMITY OF SYMPATHETIC NERVE FIBERS WITH C PAIN
FIBERS, THE PROCEDURE IS PAINFUL AND REQUIRES ANALGOSEDATION-
ANESTHESIA

INDICATIONS FOR RDN
• RDN SHOULD BE CONSIDERED IN PATIENTS WITH SEVERE RESISTANT
HYPERTENSION, DEFINED AS OFFICE SYSTOLIC BLOOD PRESSURE (SBP) ≥160
MMHG (≥150 MMHG IN PATIENTS WITH TYPE 2 DIABETES) DESPITE
TREATMENT WITH ≥3 ANTIHYPERTENSIVE DRUGS OF DIFFERENT CLASSES,
INCLUDING A DIURETIC, AT OPTIMAL DOSES
• ELEVATED OFFICE SBP SHOULD BE CONFIRMED BY AMBULATORY BLOOD
PRESSURE MONITORING
• REVERSIBLE LIFESTYLE FACTORS HAVE TO BE IDENTIFIED AND INTERFERING
MEDICATIONS SHOULD BE DISCONTINUED
• EXCLUDE, PSEUDO-RESISTANCE AND SECONDARY CAUSES FOR ELEVATED
BLOOD PRESSURE MUST BE SYSTEMATICALLY EXCLUDED
• NONINVASIVE IMAGING OF RENAL ARTERY (DUPLEX ULTRASOUND OR
MAGNETIC RESONANCE IMAGING) SHOULD BE PERFORMED TO CHECK
WHETHER THE PROCEDURE IS ANATOMICALLY FEASIBLE

CONTRAINDICATIONS TO RDN
RDN SHOULD NOT BE PERFORMED IN PATIENTS WITH:
• ANATOMICALLY UNSUITABLE RENAL ARTERIES (DIAMETER <4 MM; LENGTH <20
MM; FIBROMUSCULAR DYSPLASIA
• SIGNIFICANT RENAL ARTERY STENOSIS
• IN PATIENTS WITH AN EGFR <45 ML/MIN/1.73 M2

BENEFITS OF RDN
• CLINICAL TRIALS HAVE DEMONSTRATED THAT RDN SIGNIFICANTLY REDUCES
BLOOD PRESSURE IN PATIENTS WITH RESISTANT HYPERTENSION
• EXPERIMENTAL STUDIES AND SMALL CLINICAL STUDIES INDICATE THAT RDN
MIGHT ALSO HAVE BENEFICIAL EFFECTS IN OTHER DISEASES AND
COMORBIDITIES, CHARACTERIZED BY INCREASED SYMPATHETIC ACTIVITY,
SUCH AS LEFT VENTRICULAR HYPERTROPHY, HEART FAILURE, METABOLIC
SYNDROME AND HYPERINSULINEMIA, ATRIAL FIBRILLATION, OBSTRUCTIVE
SLEEP APNEA, AND CHRONIC KIDNEY DISEASE
• FURTHER CONTROLLED STUDIES ARE REQUIRED TO INVESTIGATE THE ROLE
OF RDN BEYOND BLOOD PRESSURE CONTROL

ONGOING RESEARCH
• THE RESISTANT ARTERIAL HYPERTENSION COHORT STUDY (RAHYCO) IS
INVESTIGATING THE EPIDEMIOLOGY OF RESISTANT HYPERTENSION AND
EVALUATING THE EFFICACY AND FEASIBILITY OF A STANDARDISED
TREATMENT REGIMEN (INCLUDING RANDOMISATION OF TWO DOSES OF
CHLORTALIDONE)
• IT IS ALSO STUDYING TWO INTERVENTIONS IN A GROUP OF NON-
COMPLIANT PATIENTS, AND WILL STUDY ENVIRONMENTAL AND GENETIC
VARIABLES OF INDIVIDUALS WITH RESISTANT HYPERTENSION WITHIN A
FAMILY DESIGN. IT PLANS TO ENROLL 200 PATIENTS AND IS DUE TO
COMPLETE IN APRIL 2018

ONGOING RESEARCH
• ST JUDE MEDICAL, INC ANNOUNCED THE START OF THE ENLIGHTNMENT
• IT IS PROSPECTIVE, RANDOMIZED, CONTROLLED STUDY OF APPROXIMATELY
4,000 PATIENTS WITH A SBP ≥160 MMHG ENROLLED AROUND THE WORLD
AT UP TO 150 SITES
• PATIENTS WILL BE RANDOMIZED TO MEDICAL THERAPY PLUS RDN OR
MEDICAL THERAPY ALONE AND WILL BE FOLLOWED FOR 5 YEARS
• PRIMARY ENDPOINTS INCLUDE MAJOR CARDIOVASCULAR EVENTS SUCH AS
HEART ATTACK, STROKE, HEART FAILURE WITH HOSPITALIZATION AND
CARDIOVASCULAR DEATH

Resistant hypertension

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