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Plavix as Medical Necessity inUnstable Angina
(Plavix sebagai Kebutuhan Medis diAngina Tidak Stabil)
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Manisfestasi klinik Atherothrombosis
Adapted from: Drouet L. Cerebrovasc Dis 2002; 13(suppl 1): 1 !.
Transientischemic attack
Angina:" Stable" Unstable
schemicstr!ke
My!cardialin"arcti!n
Peri#heral arterialdisease:" ntermittent claudicati!n" $est Pain" %angrene" Necr!sisarteri #eri"er #enyakit:
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#era$atan %umah &akit di '&arena A & 1
&' airns * et al. Can J Cardiol 1++!; 12: 12,+ +2.
Acute c!r!nary syndr!mes
1.- uta pera$atan di rumah sakit per tahun
'nstable an/ina ('A) M o ardial infar tion
( $a4e and non $a4e)
,-05000 penderita ,-05000 penderita
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Atherothrombosis &e ara bermaknamenurunkan harapan hidup
Analysis o f data from the Framingham Heart Study
AMI = Acute m yocardial infarction
Healthy History o fcardiovascular disease
History o fAMI
History ofstroke
1. P eeters et al . Eur H eart J 200 2; 23: 458466
Atherothrombosis r educes l ife expectancy b y a pproximately812 years in patients a ged over 60 years 1
Average remaining life exp ectancy a t age 60 ( men)$ata rata hara#an hidu# yang tersisa #ada usia *(laki laki)
02
46
8
10
12
1416
1820
Y e a r s
-9.2years
-7.4years
-12years
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A ute oronar & ndrome: 6ia a rata rata di7e/ara 8ropa (selama ! bulan)9 1
&' 6ro$n %8 et al. Eur Heart J 2002; 23: -0 .
9 nitial hospital sta a ounts for < 0= of the osts
+ r a
n c e
S # a i n
N e t h e r l a n
d s
t a l y
U K
% e r m a n y
0
25000
>5000
!5000
5000
105000
125000
o s t p e r p a
t i e n t ( 8 u r o s )
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" An/ka kematian dalam 30 hari = hin//a 1!= sekalipunheparin?aspirin telah diberikan.
" Adan a issue aspirin resistan e
" 6ila ter adi %e urrent is hemia5 akan menurunkan sur4i4al pasien
" emampuan identifikasi #asien A & apakah medium?hi/h risk
" Men/inplementasikan strate/i pen/obatan baru den/an men//unakanpotent anti platelet pada medium hin//a hi/h risk A & pasien
Tantangan Penanganan A,S
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Peranan Anti#latelet
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@bat @bat Antiplatelet
" hromboBane A 2 inhibitor A et lsali li a id (A&A)
" #hosphodiesterase inhibitor
Dip ridamole
" Cl oprotein (C#) b? a blo kers
#arenteral: ab iBimab5 eptifibatide5 tirofiban
" AD# re eptor anta/onists
,l!#id!grel ( Plavix )
i lopidine ( i lid 5 A/ulan 5 i urin/ )
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@ ( lo oB /enase) AD# (adenosine diphosphate)
A 2 (thromboBane A 2)
,-.P /.%$0-
ASA ,.1
A/P
A/P
,
%Pllb2llla(+ibrin!gen rece#t!r)
,!llagen thr!mbinT1A 2Activati!n
T1A 3
ara er a Antiplatelet 1
&' & hafer A . Am J Med 1++!; 101: 1++ 20+.
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6' LM AE FA7C 'A : Antithromboti rialistsG ollaboration 1
" Objective: 'ntuk menentukan efek pen/obatan anti platelet pada pasien
pasien den/an resiko tin//i untuk ter adi e adian Haskular.
" Data diteliti dari:
2 , #enelitian:" 13-5000 pasien dibandin/kan den/an anti platelet lain atau
den/an ontrol.
" ,,5000 pasien merupakan penelitian perbandin/an antiplatelet
" Hasil yang diukur I e aian 4as ular an/ seriusG: non fatal m o ardial infar tion5
non fatal stroke atau 4as ular death
&' Antithromboti rialistsG ollaboration. BMJ 2002; 32>: ,1 !.
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Antithromboti rialistsG ollaboration:Menurunkan %esiko 7on Jatal M o ardial nfar tion 1
&' Antithromboti rialistsG ollaboration. BMJ 2002; 32>: ,1 !.
,ateg!ry 4 !dds reducti!n
A ute M
#rior M
#rior stroke? A
@ther hi/h risk 9
All trials 564 K3
( p 0.0001)
1.00.-0.0 1.- 2.0,!ntr!l better Anti#latelet better
9 oronar arter disease5 peripheral arterial disease5 hi/h risk of embolism and other hi/hrisk onditions (in ludin/ hemodial sis5 diabetes mellitus5 arotid disease)
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Antithromboti rialistsG ollaboration:Menurunkan %esiko 7on Jatal &troke 1
&' Antithromboti rialistsG ollaboration. BMJ 2002; 32>: ,1 !.
,ateg!ry 4 !dds reducti!n
A ute M
A ute stroke
#rior M
#rior stroke? A
@ther hi/h risk 9
All trials 374 K3
( p 0.0001)
1.00.-0.0 1.- 2.0,!ntr!l better Anti#latelet better
9 oronar arter disease5 peripheral arterial disease5 hi/h risk of embolism and other hi/hrisk onditions (in ludin/ hemodial sis5 diabetes mellitus5 arotid disease)
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Antithromboti rialistsG ollaboration:Menurunkan %esiko Has ular Deaths 1
&' Antithromboti rialistsG ollaboration. BMJ 2002; 32>: ,1 !.
,ateg!ry 4 !dds reducti!n
A ute M
A ute stroke
#rior M
#rior stroke? A
@ther hi/h risk 9
All trials &74 K2
( p 0.0001)
1.00.-0.0 1.- 2.0,!ntr!l better Anti#latelet better
9 oronar arter disease5 peripheral arterial disease5 hi/h risk of embolism and other hi/hrisk onditions (in ludin/ hemodial sis5 diabetes mellitus5 arotid disease)
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Antithromboti rialistsG ollaboration:esimpulan
" Pemberian Anti#latelet harus di#ertimbangkan untuk diberikan secara rutin#ada #asien yang beresik! tinggi'
" Pemberian Anti#latelet menurunkan ke8adian vascular #ada #asien resik!tinggi dari:
acute my!cardial in"arcti!n (M ) dan acute str!ke
#ri!r M and #ri!r str!ke2transient ischemic attack c!r!nary artery disease (e'g' unstable angina9 heart "ailure)
#eri#heral arterial disease (e'g' intermittent claudicati!n)
high risk !" emb!lism (e'g' atrial "ibrillati!n)
.ther high risk "act!rs (e'g diabetes) &
" Pemberian Anti#latelet harus diberikan secara k!ntinyu dan 8angka#an8ang'
&' Antithromboti rialistsG ollaboration. BMJ 2002; 32>: ,1 !. 3' 6raun$ald 8 et al .J Am Coll Cardiol 2000; 3!: +,0 10!2. 5' 6ertrand M8 et al . Eur Heart J 2000; 21: 1>0! 32.
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,l!#id!grel #ada Unstable Angina
dan N!n ;ave M
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A#% 8: 6enefit lopido/rel lebih baik dari A&Adalam menurunkan M o ard nfark 1
&' Cent M. Circulation 1++,; +!(suppl ): >!,.
M!nths !" "!ll!< u#
0
1
2
3
>
-
0 3 ! + 12 1- 1 21 2> 2, 30 33 3!
, u m u
l a t i v e e v e n
t r a
t e ( 4 )
p 0.00 5 n 1+51 -
A&A 3.!=
lopido/rel 2.+=
lopido/rel
A&A 1+.2= 9%elati4e
riskredu tion
9 anal sis
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&' he '%8 &tud n4esti/ators. Eur Heart J 2000; 21: 2033 >1.
'%8: Desi/n 1
/!uble blind treatment u# t! &3 m!nths
ASA =7>537 mg !'d'
,l!#id!grel=7mg !'d'(n ? 937@)
Placeb!& tab !'d'
(n ? 95*5)
ASA =7>537 mg !'d'
/ a y &
) m
! n t h
v i s i t
@ m
! n t h
v i s i t
& 3 m ! n
t h
! r " i n a l v
i s i t
, l ! #
i d ! g r e
l
5 * * m
g l ! a
d i n g
d ! s e
5 m
! n t h
v i s i t
/ i s c h a
r g e v i s i t
& m
! n t h
v i s i t
Patients
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'%8: 6enefits lopido/rel
&' he '%8 rial n4esti/ators. N Engl J Med 2001; 3>-: >+> -02. 3' Data on file5 20025p,3 internal &% 8J 330,.
0.00
0.02
0.0>
0.0!
0.0
0.10
0.12
0.1>
0 3 ! + 12
M!nths !" "!ll!< u#
, u m m u
l a t i v e
h a A a r d r a
t e #la ebo 9(n !5303)
lopido/rel 9 (n !52-+)
20= %elati4erisk redu tion
p 0.0000+
,umulative 0vents(My!cardial n"arcti!n9 Str!ke9 !r ,ardi!vascular /eath)
kumulati" Acara(My!cardial n"arcti!n9 Str!ke9 atau Kematian Kardi!vaskular)
9@n top of standard therap (in ludin/ A&A)
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19
CURE: Efektitas SEGERA denganClopidogrel Loading Dose 1
Event rate (primary endpoint ) within rst 24 hours after r andomizationAcara tingkat (titik akhir #rimer C) dalam 36 8am #ertama setelah #engacakan
Cardiovascular death, myocardial infarction, stroke a nd
severe ischemia1. Yusuf S et al . Circulation 20 03; 107: 966972
0 2 4 6 8 10 12 14 16 18 20 22 24
Placebo
P=0.003
Clopidogrel
0.0
0.005
0.010
0.015
0.020
0.025
Hours after r andomization
C u m u l a t i v e h a z a r d r a t e s
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20
CURE: Efektitas SEGERA dan JANGKAPANJANG dengan Clopidogrel 1
Impact of clopidogrel compared with placebo on cardiovascular de ath, myocardialinfarction, stroke w ithin rst 30 d ays a nd from 30 days t o 1 2 m onthsRR = Relative risk
1. Yusuf S et al . Circulation 20 03; 107: 966972
Weeks
0.90
0.92
0.94
0.96
0.98
1.00
Months
0.90
0.92
0.94
0.96
0.98
1.00
Placebo
0 1 2 3 4
RR: 0.79 (0.670.92)p=0.003
030 days
Clopidogrel
Placebo
RR: 0.82 (0.70 0 .95)
p=0.009
31 days t o 12 m onths
Clopidogrel
12108641
P r o p o r t i o n e v e n t - f r e e
P r o p o r t i o n e v e n t - f r e e
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'%8: 6enefit an/ onsisten tak er/antun/Dari %i$a at #asien
&' lopido/rel #res ribin/ nformation5 '&5 Jebruar 2002.
Daseline
characteristics
@4erall
Dia/nosis
8le4 ard enN
& depr
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'%8: 6enefit an/ konsisten on op ofherap &tandard rombosis
9@n top of standard therap (in ludin/ A&A)
&' lopido/rel #res ribin/ nformation5 '&5 Jebruar 2002.
0.> 0.! 0. 1.0 1.2EaNard ratio (+-= )
,!nc!mitantmedicati!n2thera#y
Eeparin?LMOE
A&A
C# b? a Anta/
6eta blo ker
A 8
Lipid lo$erin/
# A? A6C
7o
Fes
100 m/
100 200m/
< 200 m/7o
Fes
7o
Fes
7o
Fes
7o
Fes
7o
Fes
+-1
11!11
1+2,
,>2
3201
11,3+
23
2032
10-30
> 13
,,>+
>>!1
101
,+,,
>- -
>.+
+.,
.-
+.2
+.+
.+
1-.,
+.+
+.2
!.3
11.2
10.+
.>
.1
11.>
,.,
11.,
+.,
10.+
13.,
10.
1+.2
12.0
11.3
.1
13.-
13.1
10.-
10.0
13.
N ,l!#id!grel E Placeb! E
0vents (4)
,l!#id!grel better Placeb! better
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-.,
11.>
20.,
>.1
+.
1-.+
*
7
&*
&7
3*
37
-!< risk M!derate risk Figh risk
M 9 s
t r !
k e ! r v a s c u
l a r
d e a
t h ( 4 )
Placeb!
,l!#id!grel
p ? *'*5
p ? *'*3
p ? *'**5
n 352,!
n ,52+,
n 15+ +
'%8: 6enefit lopido/rel #ada &emua%esiko &elama 12 6ulan
&' he '%8 rial n4esti/ators. N Engl J Med 2001; 3>-: >+> -02. 3' 6uda A* et al J Am CollCardiol 2002; 3+5 (suppl 6): >>16.
A$$ E 1.! 1.! >. $$$ G 2+= 1-= 2,=
9Absolute risk redu tionP%elati4e risk redu tion
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# '%8 &tud Desi/n
E.#en label thera#y c!uld include A/P rece#t!r antag!nist in c!mbinati!n
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# '%8 Easil setelah 30 hariCabun/an dari ardio4as ular death5 M 5 atau ur/ent
re4as ulariNation
The ,U$0 nvestigat!rs'The ,U$0 nvestigat!rs' LancetLancet August 3**&August 3**&
** 77 &*&* &7&7 3*3* 3737 5*5*/ays !" "!ll!< u#/ays !" "!ll!< u#
*'**'*
*'*3*'*3
*'*6*'*6
*'**'*
*'*B*'*B
,umulative ha ard rates,umulative ha ard rates
5*4 $$$5*4 $$$ p p ?*'*5?*'*5n?3 7Bn?3 7B
Standard thera#yStandard thera#y CC ,l!#id!grel,l!#id!grelJ standard thera#yJ standard thera#y CC
CC
including ASAincluding ASA
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# '%8 eseluruhan Easil *an/ka #an an/&e ak %andomiNe
Cabun/an dari ardio4as ular death atau M dari randomiNation hin//a akhir follo$ up P
*'&7*'&7
*'&**'&*
*'*7*'*7
*'**'*
&*&** 6*6* &**&** 3**3** 5**5** 6**6**
,umulative ha ard rates,umulative ha ard rates
5&4 $$$5&4 $$$
p p ?*'**3?*'**3n?3 7Bn?3 7B
/ays !" "!ll!< u#/ays !" "!ll!< u#aa bb
a ? median time "r!m rand!mi ati!n t! P, (&* days)a ? median time "r!m rand!mi ati!n t! P, (&* days)b ? 5* days a"ter median time !" P,b ? 5* days a"ter median time !" P,
Standard thera#yStandard thera#y CC ,l!#id!grel,l!#id!grelJ standard thera#yJ standard thera#y CC
The ,U$0 nvestigat!rs'The ,U$0 nvestigat!rs' LancetLancet August 3**&August 3**&GGu t! &3 m!nthsu t! &3 m!nths CCincludin ASAincludin ASA
&3' 4&3' 4
B'B4B'B4
# '%8
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# '%8 eamanan omplikasi perdarahan
CCincluding ASAincluding ASA
lopido/rel Q &tandard therap p 4aluestandard therap R alone R
= =
Ma or 1.! 1.> 7&
Life threatenin/ 0., 0.,
@ther Ma or 0.+ 0.,
Minor 1.0 0., 7&
PCI to end o" "ollo#$up
Ma or 2., 2.- 7&Life threatenin/ 1.2 1.3
@ther Ma or 1.- 1.1
Minor 3.- 2.1 0.03
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he %8D@ riallopido/rel for the %edu tion of 84ents
Durin/ @bser4ation
%esults
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&tud Desi/n
l o p i d o / r e
l A r m
# l a 1 e
b o
A r m
# 2 Da s
LD #la ebo S
#retreatment
LD lopido/relS
lopido/rel S
lopido/rel S
LD loadin/ dose5 # #retreatment5 % %andomiNationS on top standard therap in ludin/ A&A (32- m/)"on top standard therap in ludin/ A&A ( 1 32- m/)
$$
lopido/rel 9
#la ebo 9
12 Months
&teinhubl &5 et al. JAMA% 7o4ember 205 2002 Hol 2 5 7o 1+: 2>11 2>20
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6enefits lopido/rel *an/ka #an an/ pada pasien#
3=4 $$$
p ? *'*3
,l!#id!grelE
Placeb!E
@ M 6 ; 7 8 D 8 7 D # @ ; 7 @ ' % % 8 7 8 ( = )
M@7 E& J%@M %A7D@M TA @7
0 3 ! + 12
B'74
&&'74
(M 9 Str!ke9 !r /eath)& year results
9 @n top of standard therap in ludin/ A&AS All patients re ei4ed lopido/rel post # up to da 2
0
-
10
1-
&teinhubl &5 et al. JAMA% 7o4ember 205 2002 Hol 2 5 7o 1+: 2>11 2>20
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LA% F: Desi/n
" .b8ectives: Men/e4aluasi efektifitas dan keamanan lopido/rel5 on top of standard
therap (termasuk lo$ dose A&A5 heparin dan thrombol ti )5 pada pasienden/an a ute m o ardial infar tion (M )
" Meth!d!l!gy:
Double blind5 randomiNed5 prospe ti4e5 multi enter trial
" P!#ulasi:
Jollo$ up pada 35000 pasien den/an & ele4ation a ute M diberikan terapiselama empat min//u
" Fasil utama : #rimar endpoint adalah rate dari M dera at 0 atau 1 5 atau kematian atau
M melalui pen/amatan an/io/raph 5 atau melalui indeB hospitaliNationatau hari ke 5 mana an/ lebih dulu ika an/io/raph tidak dilakukan.
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CLARITY: Design
ASA = 150325 mg (if no ASA within prior 24 h ours) or 150162 mg, asloading doseHeparin = Unfractioned or l ow-molecular w eight heparinThrombolytic = R ecombinant plasminogen a ctivator, tenecteplase, tissueplasminogen activator, o r streptokinase
R = RandomizationASA = Acetylsalicylic a cid
STEMI = ST-elevation m yocardial infarction
ASA 75162 mg/day
Double-blind treatment for 30 days
ASA 75100 mg/day
Clopidogrel75 mg/day(n =1,500)
Placebo1 t ab/day
(n =1,500)
ASA 75162 mg/day
3 0 d a y s
A n g i o g
r a p h y
p r e -
d i s c
h a r g e
D a y 3
8
n = 3,000
R
Patients w ith acuteSTEMI
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A,S denganischemia atau terlihat resik! tinggi
atau direncanakan untuk P,
As#irin G
J L he#arin2S, -M;F C
JL %P b2 a antag!nist
/iduga A,S
As#irin G
/idiagn!sa A,S
As#irin G
JS, -M;F!r
L he#arin
A ?AEA 2002 Cuidelines 'pdate'ntuk 'A dan 7& 8M 1
J ,l!#id!grel J ,l!#id!grel
9Durin/ hospital areP lopido/rel should be administered to hospitaliNed patients $ho are unable to take A&Abe ause of h persensiti4it or ma or C intoleran eR lass a: enoBaparin preferred o4er unfra tionated heparin5 unless A6C is planned $ithin 2> hours
$ek!mendasi ,lass
1. 6raun$ald 8 et al. Ameri an olle/e of ardiolo/ (A ) and the Ameri an Eeart Asso iation(AEA) Cuidelines5 '&A: A ?AEA; 2002.
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ASA P
,l!#id!grel PR "!r @ m!nths
Deta bl!ckers P
Q
Q
-i#id l!
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The Ongoing Clopidogrel Clinical Trials ProgramCovers All Manifestations of Atherothrombosis
1. CAPRIE Steering Committee. Lancet 1996; 348: 132913392. The CURE Trial Investigators. N Engl J Med 2001; 345: 4945023. Bertrand ME et al. Circu lation 2000; 102: 62462 9
4. Steinhubl SR et al. JAMA 2002; 288: 24112420
Stroke TIA
Acute MIUnstable a ngina
Prior MIPCI/stenting
Atrial brillation
Intermittentclaudication
Peripheralvascular
intervention
CHARISMACAPRIE 1ACTIVE
COMMITCLARITYCURE 2CLASSICS 3CREDO 4
CHARISMACAPRIE 1
CAMPER
CHARISMA
CAPRIE 1MATCHACTIVECARESS
TIA = Transient ischemic at tackMI = Myocardial infarctionPCI = Percutaneous coronary intervention
Teri J M c Dermott CMI 2003
M0- PUT S0MUA ASP0K K0 A/ AN ATF0$.TF$.MD.S S
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#la4iB &eba/ai M8D AL78 8&& F #ada 'A
" #la4iB terbukti Lebih efektif dari standard therapi 'A saat ini
" 8fektifitas ter adi se/era ( dalam *am ) dan terbukti menurunkankematian dan an/ka ke adian atherothrombosis sebesar U 20 =
" 8fektifitas dipertahankan an/ka pan an/ hin//a satu tahun ( 20 3,5> = %%% ) bila tetap men//unakan #la4iB.
" in/kat keamanan an/ men/untun/kan dan efek perdarahanan/ ter adi setara den/an therap standard.
" #la4iB siner/is dikombinasikan den/an pen/obatan 'A an/ adadan tidak ter/antun/ pada ri$a at pen akit pasien5 san/atsiner/is den/an A&A.
" Dosis #raktis 1 1
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" UNSTAD-0 AN% NA" N!n ;ave M
" $0,0NT M
" $0,0NT ST$.K0
" 0STAD- SF PA/
" Dosis Plavix:
" -!ading /!se 5** mg ( 6 tab )
" Maintenance & x & ( =7 mg )
#LAH ndi ations:
7/25/2019 ACS Slide UTK PS (CURE)_Translate.ppt
38/38
E!"M# $#%"H
H#N$ &O'