JNC8 & Chlorthalidone

7/25/2019 JNC8 & Chlorthalidone

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Whats New In

Hypertension

JNC VIII & Chlorthalid


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JNC VIII

An executive summary of the ev

and desined to provide recommendations

For

All Clinicians


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!anel "ist

#ore than $%%nominees from vexpertise inCardioloyHypertension'ndocrinoloy!harmacoloyNephroloy

Clinical (rials etc)


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*oal +!

,nderlined !oints di-erent from


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0ru !rescri1ed

Population Drug Prescrib

Non Black Thiazide-type diuretic,Calcium channel blocker Angiotensin-con"erting einhibitorAC#$!, orAngiotensin receptor bloc

Black Thiazide-type diuretic,Calcium channel blocker CC


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Population Drug Prescrib

&ithDiabetes'ellitus

Thiazide-type diuretic,Calcium channel blocker Angiotensin-con"erting einhibitorAC#$!, orAngiotensin receptor bloc

&ith C(D AC#$ or A%B to impro"e kidnoutcomes)

0ru !rescri1ed


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2%3$ Hypertension *uide#anaement Alorithm


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Adults aed 4 35


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*eneral !opulation

2


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2


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0ia1etes or C60 !atients


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7trateies to 0oseAntihypertensive 0ru


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A 7tart one dru titrate tmaximum dose and then second dru

+ 7tart one dru and the

Antihypertensive 0ru


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C

+ein with 2 drus at the stime

either as 2 separate pills oa sinlepill com1ination

Antihypertensive 0ru

+lood !ressure 4 38%93


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:ole of Chlorthalidon


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(hia;ide vs (hia;ide.li"ac!hysioloical action is sclinical bene*ts are mo


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'volution of Chlorthalidone

+se o doses o .. to /.. mg dail

Dose o 01, 1. or 1 mg daily - BPreduction

2)1 mg and 1 mg daily, o3erbest e4cacy-to5side e3ect rat

6andmark Trial7 '%F$T,89#P

6andmark Trial7 A669AT

Feasibility o /)1 mgdose


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0ual #ode of action

%eduction in pe"ascular resistan

%eduction inplasma "olume


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"on term action

P:% reduction 7 theories

Interference with intracellular Ca2+ releaby nor- adrenaline

Inhibition of Rhokinase activity

Reduction in arterial edema

Reduction in vascular reactivity

:ao 77 et al Ind) J) !harmac) 3?@$ ?$B.?3 Dhu D et al Hypertension) 2%% Ee1F$@2G2??.Btext1oo< of cardiovascular medicine th 'd) 3BB/ #usso #N +ra; J #ed +


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"on half life of chlorthalidone

o Chlorthalidone has the longest elimination o /. hrs)

o The diuretic e3ect sets in ater to ; hours

reaches its ma-0 hr)

Carter B6 e


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CTD- $nternationale


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(he 7ystolic Hypertension inthe 'lderly !roram @7H'!

89#P %esearch ro

Cohort 4,736; 43% men

Age

60 yrs old; mean 71.6 yrs old

Eligibility Systolic ! 160"1# mm$g and iastolic ! m

esign o'ble blind; (lacebo control

)hera(y Chlorthalidone *atenolol as ste( "+

'ration 4. years

! change Systolic ! 1" mm$g


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ChangeinBP

(

mmHg)

Years

7H'!Chane in +lood !ressure

Placebo(n=2,371)

Active ! (n=2,3"#)

Years$ 1 2 3 % # $ 1 2 3

&'stolic BP&'stolic BP iastoliastol

Pla(n=

A(n

7H'! :esults


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7H'!G :esults

C96%T9A6$DN# :8) P6AC#B

89#P Cooperati"e %esearch roup)JAMA) 2@@2?/17;115;/=)

%% @C$!.)/= .

.)0; .

.)=/ .

.)/> .

.)>0 .

8troke

C9D

C9F

C:D

Death.) 2)/2)..)= .)/ .)> 2) 2)=

Fa"ors chlorthalidone Fa"ors placebo

7 l d f l 7


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C

umulati"e8t

roke

%ate

Per2..Pers

ons

'onths o FolloE-up

7H'!G Eatal and Non.fatal 7tro

# t lit : d ti


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#ortality :eduction

'%F$T

@ centres 9CTK and / centres chlorthalidone

9CTK group had a == higher mortality)

Patients Eere shited to chlorthalidone

6ater Eith chlorthalidone the trend Eas re"ersthe same group had a > loEer risk)

Circulation) 2

#:EI(G Impact on Lutcomes Af


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ierence eteen S 8ers's 9C

p7witchin Erom HC(D to Chlortha

'ultiple %isk Factor $nter"

%esearch roup)

'%F$T 'ultiple %isk Factor

$nter"ention Trial? 8$special

#ultiple :is< Eactor Intervention


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#ultiple :is< Eactor InterventionChanges From Baseline at 48 Mont

#rnst '#, et al) #y"ertension) .22

"or $nteractio

"or $nteraction )..2

"or $nteraction H )..2

#ultiple :is< Eactor Intervention


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pComparison of Diuretic Therap

Ad

Dorsch 'P, et al) #y"ertensio

Chlorthalido

ne9CTKDrug8topped

Chlorthalidone "s DrugH )...29CTK "s Drug 8toppedChlorthalidone "s 9CTK

AdJusted estimates Eere controlledor by age, race, smoking status,'%F$T randomized group, diuretic

dose, 8BP, 6D6, 9D6, and baseline


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Chlorthalidone 7afety

>#lectrolyteimbalance

>9ypokalemia>6ipid pro*le>9yperglycemi

Indian 'xperiencewith low dos
http://www.google.co.in/imgres?imgurl=http://www.hypertension-bloodpressure-center.com/images/malignant_hypertension.jpg&imgrefurl=http://www.hypertension-bloodpressure-center.com/hypertension-symptoms.html&usg=__rquxM6c41KRCGPcw9GOqbB_k64U=&h=283&w=300&sz=57&hl=en&start=18&zoom=1&tbnid=IYGIzLJvFLAOkM:&tbnh=109&tbnw=116&prev=/images?q=hypertension&hl=en&sa=G&gbv=2&tbs=isch:1&itbs=1


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chlorthalidone @C(0

5at're o st'dy 'ration 5o. o (atr

1 6." mg Chlorthalidone

6." mg Chlorthalidone : atenolol

"4 ees 3

" 6." mg Chlorthalidone :2eto(rolol


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7+! reduction with monotherap

p valu



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p valu

'l t l t h


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'lectrolyte chane

St'dy =ro'(s 8isit Sodi'm !otassi'm

Chlorthalidoneaseline 13.37 4."1

End 13."# 3.#7

Pareek et al, Current 'edical %esearch and pinions

A""HA( report on hypo


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A""HA( report on hypo


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p p

Trials lasting less than a year ha"e shoEn s

change in lipid le"els, 6ong term studies hato shoE ad"erse e3ect on lipid concentratio

8maller doses noE in use do not alter lipid p

'-ect on 1lood suar in India


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'-ect on 1lood suar in Indiatrial

St'dy =ro'(s 8isit >S

Chlorthalidoneaseline 101.4# 137.13

End 10.7 13."4

Pareek et al, Current 'edical %esearch and pini

Hyperlycemia with


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yp ychlorthalidone

A669AT

There Eas no e3ect o change in F le"el onand renal outcomes)

89#P

NeE cases o diabetes >)/ "s 0)1 in place No signi*cant increase in C:D mortality com

urEitz et al Ann $nt 'ed 22>7 0;, 2@@, Paul ( E

C(0 vs HC(D


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C(0 vs HC(D

&hich EayL

Potency


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Potency

Chlorthalidone is 2)1 to ). times as potent ahydrochlorothiazide)

Carter +" et

9CTK 1.mg 1mg2)1mg

Chlorthalidone 1mg 2)1m/)1 mg

7uperior to HC(D


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A randomized, single blinded clinical trial sthat, ater > Eeeks patients Eho Eere takmgMday chlorthalidone e


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+etterniht time control of +

5ighttime mea*mm o $g

Chlorthalidone " mg?day -13.

$ydrochlorothiaide 0 mg?day -6.4

The higher potency o chlorthalidone resulted in duration o action that pro"ided night time bloodcontrol and hence Eas e3ecti"e in pro"iding addiprotection rom stroke and myocardial inarction

+arry "C Hy

Pleiotropic bene*ts o


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Chlorthalidone

%educes platelet aggregationess potential o clot ormation

Better blood oE

Promotes angBetter blood$ess load o

%educes "ascular permeabilityBetter blood supply

$ess load on heart

etter circ'latory (erormance

ess load on heart

%yan &oodman

Chlorthalidone O)) Cl


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Apart

'illions o hypertensi"e patients ha"e bea less e3ecti"e drug 9CTK! that almostdid not protect them as Eell as CTD Eou

Norman Kaplan Hypertension Octobe

Clinical expert opinio


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Clinical expert opinio

0r Henry +lac

JNC8 & Chlorthalidone

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