resistant Hypertension NKFDOGI

8/12/2019 resistant Hypertension NKFDOGI

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Lady Davis

Institute

Resistant hypertension

Ernesto L. Schiffrin CM, MD, PhD, FRSC, FRCPC Physician-in-Chief, Sir Mortimer B. Davis-Jewish General Hospital,Canada Research Chair in Hypertension and Vascular Research,

Lady Davis Institute for Medical Research, Vice-Chair, Department of Medicine, McGill University, Montreal, PQ, Canada.


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Vital signs: prevalence,treatment, and control of HTN United States,1999-2002 and 2005-2008

Center for Disease Control and Prevention (CDC) MMWR Morb Mortal 2011;60:103-108.


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Prevalence of resistant hypertension in the United States, 2003-2008 (average of 2 out 3 measures by a physician)

Persell SD. Hypertension 2011; 57: 1076-1080.


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Resistant vs refractory hypertension

Resistant hypertension is hypertension that does respond to adequate doses of 3-4 or more antihypertensive drugs. It represents 10-15% of the general hypertensive

population. Refractory hypertension is defined as BP that

not

remains uncontrolled after 3 visits to a hypertension clinic within a minimum 6-month follow-up period. Secondary causes of hypertension, obesity, diabetes,sleep disordered breathing and excess salt intake oruse of AINS drugs are among some of the findingsassociated with resistant or refractory hypertension.


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Clinical features of 8295 patients with resistant hypertension classified on the basis of ABPM

Prevalence of resistant hypertension in the Spanish ABPM registry

Resistance defined by BP in office 140/90 mmHg and antihypertensive drugs

3

12.2% of 68,045

After ABPM: 62.5% were

After ABPM :55.9%

true resistant 130/80 mmHg

135/85 mmHg

Selected population


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Calhoun DA et al. Hypertension 2008


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Endothelial dysfunction in resistant hypertension

Quinaglia T et al. Journal of Human Hypertension doi:10.1038/jhh.2011.43


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Resistant hypertension with or without cerebral microangiopathy

Schmieder RA et al. J Clin Hypertens. 2011;13:582 587.


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How to approach resistant hypertension

The general treatment approach: 1.adding or titrating diuretic therapy,

2.changing the diuretic class to one appropriate for the patie nts

kidney function,

3.using medications with complementary mechanisms of action,

and

4.adding a mineralocorticoid antagonist to the antihypertensive

drug regimen.


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How to approach resistant hypertension

1. RAS blocker + diuretic + CCB + MR antagonist with or without a beta-blocker

Thiazide diuretics: chlorthalidone @ 25 mg d, preferred for

most patients.

CKD: loop diuretic, most commonly furosemide at 20 mg to

40 mg twice daily.

Vasodilators, centrally acting antihypertensive agents, and

alpha-adrenergic blockers added if failure to control BP.

2.

3.

4.


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How to approach resistant HTN Adherence needs to be assessed by asking the

patient about medication use, perceptions about medication efficacy, and presence of adverse effects, if any. Patients must be seen every 4 to 8 weeks,with more frequent visits for patients with

uncontrolled BP.


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Resistant HTN treatment Use of a MR antagonist in addition to a

diuretic, particularly chlorthalidone, in addition to a full dose of a RAS blocker and a CCB is usually associated with control rates of resistant hypertension >80%.


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Spironolactone in Patients With Resistant Arterial Hypertension (ASPIRANT)

Vclavk J et al. Hyper tens ion . 2011;57:1069-1075.


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Spironolactone in Resistant Hypertension

Vclavk J et al. Hypertension . 2011;57:1069-1075.


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Refractory hypertension

Acelajado MC et al. J Clin Hypert 2012;14:7 12


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Refractory hypertension



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Response to MR antagonist



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Refractory hypertension: mechanisms No evidence of greater fluid retention in

refractory HTN vs controlled resistant HTN since aldosterone or PRA levels not suppressed Greater role of increased cardiac output and or vascular resistance: enhanced sympathetic drive and or increased peripheral resistance secondary to local or circulating pressor agents?


BP i h ET i


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BP response to treatment with ET A antagonist compared to guanfacine

Change in siSBP

Change in ASBP Change in ADBP

Bakris G L et al. Hypertension 2010;56:824-830.

ASBP over 24h

Figure 2. Mean change from baseline in sitting systolic BP over time. Observed values at each time point are displayed.


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New approaches to refractory HTN Catheter-Based Radiofrequency Renal

Sympathetic Denervation Baroreceptor stimulation


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l h i d i i i i h


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Renal sympathetic denervation in patients with treatment- resistant hypertension (The Symplicity HTN-2 Trial): a

randomised controlled trial Simplicity HTN- 2 investigators ( Murray D Esler) Lancet

376;1903-1909 2010:

Objective: Activation of the sympathetic renal system is involved in the pathogenesis of hypertension

RCT in patients wint BP>150 mmHg taking 3 drugs: denervation + Rx or Rx alone

Measured systolic BP at 6 months Procedures: Catheter SYMPLICITY in renal arteries

renal

4-6 low-intensity stimulations on the renal artery BP 178/97 mmHg in patients 57-year old (male=60%) taking

mean of 5.2 drugs (35% more than 5 ) a


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Symplicity HTN-1 Investigators Catheter-Based Renal Sympathetic Denervationfor Resistant Hypertension: Durability of Blood Pressure Reduction Out to 24 Months

153 patients with catheter-based renalsympathetic denervation at 19 centers Hypertension . 2011;57:911-917.


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BP changes after renal sympathetic denervation over 24-months of follow-up

Krum H. et al. Hypertension . 2011;57:911-917.


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Randomized controlled clinical trials Simplicity HTN 3 DEPART ReSET MIRT DENER-HTN PRAGUE-15 INSPIRE

Recruiting Y Y Y Y Y Y N

Intervention RDN RDN RDN PVI+RDN RDN RDN RDN

No. patients 530 120 70 150 120 150 230

Catheter Simplicity Simplicity Simplicity THERMOCOOL Simplicity Simplicity TBD

Completion 2013 2014 2012 2012 2014 2013 2016

Country USA Belgium Denmark Russia France Czech Rep. Europe

Renalfunction

mGFR/cys C eGFR/mGFR

Imaging renalarteries

Arteriogr (6)

AngioCT (12, 24, 36)


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Center requirements for application of RDN in refractory HTN

Modified from Joint UK Societies Consensus on RDN for treatment-resistant HTN

Experience Management of resistant hypertension High volume interventional cardiology/radiology

Protocol Written protocol for work-up, procedure & f/uWritten informed consent and ethics approval

Plans for management of complications Infrastructure High quality CT/MRI

Hemodynamics lab

Multidisciplinary

team

HTN specialists experienced in managing resistant HTN

Interventional cardiologists/radiologists experienced inRDN and nephrologists and vascular surgeons

Transparency Participation in registration program


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Carotid Baroreceptor Stimulation, Sympathetic activity, Baroreflex function and Blood pressure in Hypertensive Patients

Heusser K et al. Hypertension 2010;55:619-626


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Conclusion Diagnosis, including ABPM

Exclude secondary causes

3 drugs (RAS inhibitor, CCB, diuretic) + MR blocker

Adherence to treatment, salt intake

F/u and only then consider invasive treatments


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Gracias

resistant Hypertension NKFDOGI

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