Optimizing Therapy in Heart Failure 1-Final
Transcript of 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 $nd oint" All-Cause %ortality
Death or Hospitali7ation Due to H#
Ris) of all-cause mortality reduced .y 0>3in group with CR+ and /CD ,p F
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HFSA 3)!) Pra.ti.e BuidelineHFSA 3)!) Pra.ti.e Buideline
=arfarin=arfarin ;a',a'in (.oal "NR 20:30);a',a'in (.oal "NR 20:30) is 'ecoendedis 'ecoended,o' all atients/,o' all atients/
& ;it& # and c&'onic o' docuented a'o
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HFSA 3)!) Pra.ti.e BuidelineHFSA 3)!) Pra.ti.e Buideline
0ong*Term Antithrom
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HFSA 3)!) Pra.ti.e BuidelineHFSA 3)!) Pra.ti.e Buideline
Anti*arrhythmi.Anti*arrhythmi.
Anti-arrh$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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