optimizing therapy in heart failure 1-final

8/9/2019 Optimizing Therapy in Heart Failure 1-Final

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Optimizing Therapy In Heart FailureOptimizing Therapy In Heart Failure

Dr Devendra Khandke MDDr Devendra Khandke MD

Head- Medical ServicesHead- Medical Services

Alembic Pharmaceuticals LtdAlembic Pharmaceuticals Ltd


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Epidemiology of HF in IndianEpidemiology of HF in Indian

PopulationPopulation

Prevalence: 1.8 croresPrevalence: 1.8 crores

ncidence: 1!." lakhs #er $earncidence: 1!." lakhs #er $ear

%ommon %auses:%ommon %auses:

& 'heumatic Heart Disease: !(.8)'heumatic Heart Disease: !(.8)

& schemic Heart disease * H$#ertension:schemic Heart disease * H$#ertension:

(".()(".()


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Pathogenesis and Sequel of Heart FailurePathogenesis and Sequel of Heart Failure

Adapted from Cohn J N Engl J Med.!""#$%%&'(")*("+

Coronary arterydisease

Hypertension

Cardiomyopathy

Valvulardisease

Left

ventricular

dysfunction

Non-cardiacfactors

Remodeling

Low

ejection

fraction

Arrhythmia

Death

ump

failure

!ymptoms"Dyspnea#atigue$dema

Chronicheartfailure

, Neurohormonalstimulation

, $ndothelialdysfunction

, Vasoconstriction

, Renal sodiumretention


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-entri.ular /emodeling in CHF-entri.ular /emodeling in CHF

Jessup, NEJM 2003


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0loyd*Jones 12 et alCirculation. 3))3$!)#'%)#+*43

)

&

!)

!&

3)

3&

Attained age 5years6

Cumulati7e

ris8 596

%en

()

3)9 0ifetime ris8 for HF after age ()3)9 0ifetime ris8 for HF after age ()

&omenFramingham Heart Study

&)&) #) 4) +) "))

&

!)

!&

3)

3&

)

0ifetime ris8 for HF for gi7en inde: age

is .umulati7e through age "( years

() &)&) #) 4) +) ")


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Hypertension is the ;o ! ris8 fa.tor for HFHypertension is the ;o ! ris8 fa.tor for HF

3)

()

#)

)

HT;

Population*

attri


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Ameri.an Heart Asso.iation

'In people diagnosed ?ith heart failure@ suddendeath o..urs at # * " times the rate of the general

population

, In* patient mortality rate !st

year post diagnosis' &*3)9

, Out*patient mortality rate !st year post diagnosis' 3)9

, &*year mortality rate is &)9

, Ea.h re*hospitalization in.reases mortality


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1iagnosis of HF1iagnosis of HF

Histor$: cardiom$o#ath$+ ,alvular heart disease+Histor$: cardiom$o#ath$+ ,alvular heart disease+alcohol use+ h$#ertension+ Prior M+ Aninaalcohol use+ h$#ertension+ Prior M+ Anina

SS: /0ertional d$snea+ ortho#nea+ PD+ 2atiue+SS: /0ertional d$snea+ ortho#nea+ PD+ 2atiue+#al#itations+ nocturia+ #ulmonar$ rales+ H3+#al#itations+ nocturia+ #ulmonar$ rales+ H3+he#ato4uular re2le0+ edema+ S5 allo#he#ato4uular re2le0+ edema+ S5 allo#

nvestiations: %6%+ /lectrol$tes+ 'enal 2unctionnvestiations: %6%+ /lectrol$tes+ 'enal 2unction

test+ He#atic 2unction test+test+ He#atic 2unction test+ 6-t$#e natriuretic6-t$#e natriuretic#e#tides+#e#tides+ Do##ler and (-D ecocardiora#h$+ /%7+Do##ler and (-D ecocardiora#h$+ /%7+%ardiac M'+ Aniora#h$+ Heart catheteriation+%ardiac M'+ Aniora#h$+ Heart catheteriation+'iht ventricular endom$ocardial bio#s$'iht ventricular endom$ocardial bio#s$


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iomar8ers in HFiomar8ers in HF

Most commonl$ biomarkers 2or dianosis o2Most commonl$ biomarkers 2or dianosis o2sus#ected H9 are natriuretic #e#tidessus#ected H9 are natriuretic #e#tides

S$nthesied as #ro-6P cleaved b$ corin intoS$nthesied as #ro-6P cleaved b$ corin intoinactive -terminal #ro6P 3-#ro6P; andinactive -terminal #ro6P 3-#ro6P; and

bioloicall$ active 6Pbioloicall$ active 6P

6P #roduced b$ vascular m$ocardium released in6P #roduced b$ vascular m$ocardium released inres#onse to #ressure and volume stressres#onse to #ressure and volume stress

Active 6P causes vasodilation+ natriuresis andActive 6P causes vasodilation+ natriuresis andantaonism o2 'AASantaonism o2 'AAS


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Assess LV Function (echo, gated RNA)

EF < 40%-systolic dysunction

EF 40-!!%-systolic"diastolic dysunction

EF #!!%-diastolic dysunction

Assess Volu$e tatus

igns and y$&to$s o

Fluid Retention

No igns and y$&to$s

o Fluid Retention

Loo& 'iuetic"- *hia+ide

(titate to euole$ic state)

AE inhi.ito"AR/ i AE intoleanto$.ination R i 1F, hos&itali+ation o -.loc2e intoleant

&ionolactone" E&leenone(N31A lass -V 1F"EFAdd 'igoin o

sy$&to$ contol

Assess$ent 8 *eat$ent o honic 1F

-.loc2e (N31A -V)


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HFSA 3)!) Pra.ti.e BuidelineHFSA 3)!) Pra.ti.e Buideline

HF /is8 Fa.tor Treatment BoalsHF /is8 Fa.tor Treatment Boals

'isk 9actor'isk 9actor 7oal7oal

H$#ertensionH$#ertension 7enerall$ < 15=8=7enerall$ < 15=8=

DiabetesDiabetes See ADA uidelinesSee ADA uidelines11

H$#erli#idemiaH$#erli#idemia See %/P uidelinesSee %/P uidelines((

nactivit$nactivit$ (=-5= min. aerobic 5-! 0 >k.(=-5= min. aerobic 5-! 0 >k.

?besit$?besit$ @eiht reduction < 5= 6M@eiht reduction < 5= 6M

AlcoholAlcohol MenMen ( drinksda$+ >omen 1 ( drinksda$+ >omen 1

SmokinSmokin %essation%essationDietar$ SodiumDietar$ Sodium Ma0imum (-5 da$Ma0imum (-5 da$

11

Diabetes %are (==BC (: SE-SE(Diabetes %are (==BC (: SE-SE( ((FAMA (==1C (8!:(E8B-"FAMA (==1C (8!:(E8B-"


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Pharma.ologi.al Therapies for HFPharma.ologi.al Therapies for HF DiureticsDiuretics A%/ inhibitorsA%/ inhibitors A'6A'6 6eta 6lockers6eta 6lockers K s#arin diuretic aentsK s#arin diuretic aents

& 3riamterene+ Amiloride+ S#ironolactone Aldosterone inhibitorsAldosterone inhibitors

& /#lerenone DiitalisDiitalis ,asodilators,asodilators

& H$dralaine+ itro#russideH$dralaine+ itro#russide Positive ionotro#ic aentsPositive ionotro#ic aents

& do#amine+ dobutamine+ milrinone+ imamrinonedo#amine+ dobutamine+ milrinone+ imamrinone 'ecombinant 2orm o2 human brain natriuretic #e#tide: esiritide'ecombinant 2orm o2 human brain natriuretic #e#tide: esiritide

& Potent vasodilator that reduces ventricular 2illin #ressuresPotent vasodilator that reduces ventricular 2illin #ressuresand im#roves cardiac out#utand im#roves cardiac out#ut

Anti-arrh$thmic aentsAnti-arrh$thmic aents


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(eta (loc)ers in H#- A aradigm !hift


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Heart Failure So.iety of Ameri.a 5HFSA6 Pra.ti.e Buidelines J Cardiac Fail !"""$&'%&4*%+3

*Heart Failure So.iety of Ameri.a 5!"""6

The single most significant addition to theThe single most significant addition to the

pharmacological management of heartpharmacological management of heart

failure since the publication of previousfailure since the publication of previous

guidelinesguidelines ACCDAHAACCDAHA involves the use ofinvolves the use ofbeta-receptor antagonists.beta-receptor antagonists.


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Effe.t of eta lo.8ade on Out.ome

in Patients =ith HF and Post*2I 0-1

3%9 mortality 5p >)%!63& I1post*2I0-1

.ar7edilolCAP/ICO/;&

%&9 mortality 5p > ))!(63& I1se7ere.ar7edilolCOPE/;ICS(

%(9 mortality 5p > ))#363)) G1mildD

moderate

metoprolol

su..inate

2E/IT*HF%

%(9 mortality 5p )))!6!) G1moderateD

se7ere

))46

#3&*

3& I1

mildD

moderate

.ar7edilolS Car7edilol!

*utcome

+arget

Dose ,mg

H#

!everityDrug!tudy

! Colu..i =S et al Cir.ulation !!"#$"('3+))*#

3 CIIS II In7estigators 0an.et !"""$%&%'"*!%

% 2E/IT*HF Study Broup 0an.et !"""$%&%'3))!*4

( Pa.8er 2 et al ; Engl J 2ed 3))!$%((!#&!*+

& The CAP/ICO/; In7estigators 0an.et 3))!$%&4'!%+&*")


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!ymptoms %or.idity %ortality

/ncrease dose No 01-023 N!

of AC$ inhi.itor0

effect

Add -.loc)ade4 41-523 523

!"ac#er M et al. Circulation. !$$$%!&&'()!(*()!+.(,echat " et al. Circulation. !$$+%$+'!!+*!!$!.

Effe.ts of AddingEffe.ts of Adding *lo.8ers 7s In.reasing*lo.8ers 7s In.reasingACE Inhi


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2etoprolol C/D0 /andomized2etoprolol C/D0 /andomizedInter7ention Trial in Congesti7e HeartInter7ention Trial in Congesti7e Heart

FailureFailure 52E/IT*HF652E/IT*HF6Mortality CV deaths Sudden death Death due toworsening HF

*#)9

*&)9

*()9

*%)9

*3)9

*!)9

)9M o rta lity C V d e a th s S u d d e n d e a th D e a th d u e to w o rse n in g H F

Ris)reduction,3-

%(9 %+9 (!9("9

9ild to $odeate 1F: LVEF < 40%

N ; 5= t ; = yea

9eto&olol R">L (600 $g od) s &lace.o

0an.et !"""$ %&%' 3))!*3))4


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2E/IT*HF' 2ortality !"+3 age #& years

9

Patients

Ris)

reduction

;03


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/ d i d E l i f S i f


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Reduces total mortality .y 2:


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2ortality /edu.tions ?ith ACE * I2ortality /edu.tions ?ith ACE * I

0

5

10

15

20

25

30

Re

lativeRiskRedu

ction(%)

CONSENSUS SOLV S!VE !"RE #O$En > 3&% n > (33+ n > 33%! n > !"+# n > %&44

CO;SE;SS' NEJM !"+4$%!#'!(3"*(%&@ SO0-1' NEJM !""!$%3&'3"%*%)3@ SA-E' NEJM !""3$%34'##"*#44

AI/E' ,ancet!""%$%(3'+3!*+3+@ HOPE' ,ancet3)))$%&&'3&%*3&"

T l i t i th 2 t St di d A tT l i t i th 2 t St di d A t


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Telmisartan is the 2ost Studied AmongstTelmisartan is the 2ost Studied Amongst

A/s in 2ortality and 2or


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Telmisartan has a nique Pharma.ologyTelmisartan has a nique Pharma.ology

Profile in its Class 5A/6Profile in its Class 5A/6

lasmahalf-life,h

urnier@ runner ,ancet.3)))$%&&'#%4L#(&$ runner J um 0pertens.3))3$!#5Suppl 36'S!%LS!#$ Na8uta et al1nt J Clin "harmacol2es.3))&$3&'

(!L(#$ =ienen et al 3r J "harmacol.!""%$!!)'3(&L3&3$ Song@ =hite Formular0.3))!$%#'(+4L(""$ Asmar 1nt J Clin "ract.3))#$#)'%!&L%3)$ Israili J um 0pertens.3)))$!(5Suppl !6'S4%LS+#$ enson et al 0pertension. 3))($(%'""%L!))3

Longest plasma half-life

$pro-

sartan

Lo-

sartan

Val-

sartan

Cande-

sartan

*lme-

sartan

/r.e-

sartan

+elmi-

sartan

Volumeofdistri.ution,L %ost lipophilic

5high tissue penetration6

&))&))

Cande-

sartan

$pro-

sartan

Val-

sartan

*lme-

sartan

Lo-

sartan

/r.e-

sartan

+elmi-

sartan

A.ti7e meta


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et&odset&ods& Patients under>ent double-blind randomiationPatients under>ent double-blind randomiation

8!"B assined to 1= m o2 rami#ril #er da$8!"B assined to 1= m o2 rami#ril #er da$ 8!E( assined to 8= m o2 telmisartan #er da$8!E( assined to 8= m o2 telmisartan #er da$ 8!=( assined to both drus combination8!=( assined to both drus combination

thera#$;thera#$;

& Primar$ com#osite outcome GPrimar$ com#osite outcome G death 2rom cardiovascular causesdeath 2rom cardiovascular causes m$ocardial in2arctionm$ocardial in2arction StrokeStroke hos#italiation 2or heart 2ailure.hos#italiation 2or heart 2ailure.

O;TA/BETO;TA/BET

TrialTrial


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O;TA/BETO;TA/BET

%onclusion:%onclusion:

3elmisartan >as euivalent to rami#ril in #atients3elmisartan >as euivalent to rami#ril in #atients>ith vascular disease or hihrisk diabetes and>ith vascular disease or hihrisk diabetes and

>as associated>as associated >ith less anioedema.>ith less anioedema.

; Engl J 2ed 3))+$%&+'!&(4*&"


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%ombination o2 A'6 and 6eta 6lockers%ombination o2 A'6 and 6eta 6lockersin Heart 9ailurein Heart 9ailure


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HFSA 3))# Pra.ti.e Buideline 54!(*4!&6

Pharma.ologi. Therapy'

Aldosterone AntagonistsAn aldosterone antagonist is recommended for

patients on standard therapyB including diureticsB

who have"

NHA class /V H# ,or class ///B previously class /V

due to LV systolic dysfunction ,LV$# 523

*ne should .e considered in patients post-%/

with clinical H# or dia.etes and an LV$# :13who are on standard therapyB including an AC$

inhi.itor or an AR(< Strength of Evidence = A

Adapted from' Adams NF@ 0indenfeld J@ et al HFSA 3))# Comprehensi7e

Heart Failure Buideline J Card Fail 3))#$!3'e!*e!33

HFSA 3)!) Pra.ti.e Buideline 54!(*4!&6


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Aldosterone Antagonists in HF

RAL$! ,Advanced H# $H$!E! ,ost-%/

!pironolactone

lace.o

%onths

RR F 1


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HFSA 3)!) Pra.ti.e Buideline 5436HFSA 3)!) Pra.ti.e Buideline 5436

Pharma.ologi. Therapy' Su


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A*HeFT All*Cause 2ortality

!urvival

3

Days !ince (aseline Visit

(%9 1e.rease in 2ortality

#i6ed Dose /!DNGHDN

lace.o

F 1


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HFSA 3))# Pra.ti.e Buideline 543(6

Pharma.ologi. Therapy' 1iureti.s

Restoration of normal volume status may reIuire multipleadjustmentsidened J'S interval 1(= ms;1(= ms;

& Severe L, s$stolic d$s2unction L,/9Severe L, s$stolic d$s2unction L,/9 ith reducedL,/9 and J'SL,/9 and J'S 1!= ms >ho have HA - H9 s$m#toms.1!= ms >ho have HA - H9 s$m#toms.


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C/T Impro7es Guality of 0ife andC/T Impro7es Guality of 0ife and

;HA Fun.tional Class;HA Fun.tional Class

*P


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C/T in Patients ?ith Ad7an.ed HF andC/T in Patients ?ith Ad7an.ed HF and

a Prolonged G/S Inter7al'a Prolonged G/S Inter7al'

CO2PA;IO;CO2PA;IO;

(ristow %R et al< N $ngl K %ed 411:J521"40:1-21

rimary $nd oint" All-Cause %ortality

Death or Hospitali7ation Due to H#

Ris) of all-cause mortality reduced .y 0>3in group with CR+ and /CD ,p F


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=arfarin=arfarin ;a',a'in (.oal "NR 20:30);a',a'in (.oal "NR 20:30) is 'ecoendedis 'ecoended,o' all atients/,o' all atients/

& ;it& # and c&'onic o' docuented a'o


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0ong*Term Antithrom


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Anti*arrhythmi.Anti*arrhythmi.

Anti-arrh$thmic aents+ includin amiodarone-Anti-arrh$thmic aents+ includin amiodarone- notnotrecommendedrecommended2or the #rimar$ #revention o2 sudden death2or the #rimar$ #revention o2 sudden deathin #atients >ith H9in #atients >ith H9

Strength of Evidence = AStrength of Evidence = A

n #atients >ith H9 and an %D+ amiodaronen #atients >ith H9 and an %D+ amiodarone ma$ bema$ beconsideredconsideredto reduce the 2reuenc$ o2 recurrentto reduce the 2reuenc$ o2 recurrents$m#tomatic arrh$thmias causin %D shockss$m#tomatic arrh$thmias causin %D shocks

Strength of Evidence = CStrength of Evidence = C

'outine use o2 amiodarone thera#$ 2or as$m#tomatic'outine use o2 amiodarone thera#$ 2or as$m#tomaticarrh$thmias that are not 2elt to contribute to H9 orarrh$thmias that are not 2elt to contribute to H9 orventricular d$s2unctionventricular d$s2unction is not recommendedis not recommended

Strength of Evidence = BStrength of Evidence = B

-entri.ular Assist 1e7i.es-entri.ular Assist 1e7i.es


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-entri.ular Assist 1e7i.es-entri.ular Assist 1e7i.es

,ADs commonl$ used,ADs commonl$ used

& 6ride the acutel$ 2ailin heart to eventual heart trans#lantation6ride the acutel$ 2ailin heart to eventual heart trans#lantation& ot trans#lant candidates+ >ho other>ise >ould dieot trans#lant candidates+ >ho other>ise >ould die

Abiomed 6,S !=== circulator$ su##ort s$stem Abiomed+ nc+Abiomed 6,S !=== circulator$ su##ort s$stem Abiomed+ nc+

Danvers+ Mass;+ >hich is t$#icall$ used 2or short-term su##ortDanvers+ Mass;+ >hich is t$#icall$ used 2or short-term su##ort

Abiomed A6!=== circulator$ su##ort s$stem Abiomed+ nc;Abiomed A6!=== circulator$ su##ort s$stem Abiomed+ nc;

%entrima or Levitroni0 s$stem 3horatec+ Pleasanton+ %ali2;%entrima or Levitroni0 s$stem 3horatec+ Pleasanton+ %ali2;

3horatec #aracor#oreal and intracor#oreal L,AD and ',AD3horatec #aracor#oreal and intracor#oreal L,AD and ',AD3horatec;3horatec;

ovacor L,AD @orld Heart nc+ ?akland+ %ali2;ovacor L,AD @orld Heart nc+ ?akland+ %ali2;

HeartMate L,AD 3horatec;HeartMate L,AD 3horatec;


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HFSA 3)!) Pra.ti.e Buideline 5+!6HFSA 3)!) Pra.ti.e Buideline 5+!6

Heart Failure Patient Edu.ationHeart Failure Patient Edu.ation

& tt is recommendedis recommendedthat #atients >ith H9 and theirthat #atients >ith H9 and their2amil$ members or careivers receive2amil$ members or careivers receiveindividualied education and counselin thatindividualied education and counselin thatem#hasies sel2-care.em#hasies sel2-care.

& 3his education and counselin should be delivered3his education and counselin should be deliveredb$ #roviders usin a team a##roach.b$ #roviders usin a team a##roach.

& 3eachin should include skill buildin and taret3eachin should include skill buildin and taretbehaviors.behaviors.

Strength of Evidence = BStrength of Evidence = B

Adapted from'


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optimizing therapy in heart failure 1-final

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