acs slide utk ps (cure)_translate.ppt

7/25/2019 ACS Slide UTK PS (CURE)_Translate.ppt

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Plavix as Medical Necessity inUnstable Angina

(Plavix sebagai Kebutuhan Medis diAngina Tidak Stabil)


2/38

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:


3/38

#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


4/38

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 )


6/38

" 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


7/38

Peranan Anti#latelet


8/38

@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/ )


9/38

@ ( 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+.


10/38

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 !.


11/38

Antithromboti rialistsG ollaboration:Menurunkan %esiko 7on Jatal M o ardial nfar tion 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)


12/38

Antithromboti rialistsG ollaboration:Menurunkan %esiko 7on Jatal &troke 1



A ute M

A ute stroke

#rior M

#rior stroke? A

@ther hi/h risk 9

All trials 374 K3

( p 0.0001)




13/38

Antithromboti rialistsG ollaboration:Menurunkan %esiko Has ular Deaths 1



A ute M

A ute stroke

#rior M

#rior stroke? A

@ther hi/h risk 9

All trials &74 K2

( p 0.0001)




14/38

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


16/38

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


17/38

&' 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


18/38

'%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)


19/38

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


20/38

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


21/38

'%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


22/38

'%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


23/38

-.,

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


24/38

# '%8 &tud Desi/n

E.#en label thera#y c!uld include A/P rece#t!r antag!nist in c!mbinati!n


25/38

# '%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


26/38

# '%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


27/38

# '%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


28/38

he %8D@ riallopido/rel for the %edu tion of 84ents

Durin/ @bser4ation

%esults


29/38

&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


30/38

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


31/38

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.


32/38

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


33/38

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.


34/38

ASA P

,l!#id!grel PR "!r @ m!nths

Deta bl!ckers P

Q

Q

-i#id l!


35/38

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


36/38

#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


37/38

" 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:


38/38

E!"M# $#%"H

H#N$ &O'

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