The Pivotal Role of Platelets in Primary PCI Paul Martin PhD Senior Medical Affairs Scientist...
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Transcript of The Pivotal Role of Platelets in Primary PCI Paul Martin PhD Senior Medical Affairs Scientist...
The Pivotal Role of Platelets in The Pivotal Role of Platelets in Primary PCI Primary PCI
Paul Martin PhD
Senior Medical Affairs Scientist
Centocor/ Eli Lilly
UK/Eire/Nordic regions
Reperfusion…..by Design Reperfusion…..by Design Reperfusion…..by Design
No
. live
s s
aved
pe
r 10
00
pati
en
ts
tre
ate
d w
ithth
rom
bo
lyti
cs
(b
ase
d o
n 3
5-d m
ort
ality
ra
tes
)
Additional Lives Saved by Reducing Treatment Delay
Time from onset of symptoms (h) 0 - 1 1 - 2 2 - 3 3 - 6 6 - 12 12 - 24
Average delay (h) 0.75 1.60 2.17 4.03 8.37 18.00
Boersma E et al. Lancet. 1996;348:771-775.
70
60
50
40
30
20
10
0
Procoagulant Effects of Fibrinolytic TherapyProcoagulant Effects of Fibrinolytic Therapy
Adapted with permission from Moliterno DJ, Topol EJ. Thromb Haemost. 1997;78:214-219.
Fibrin-ThrombinPlateletsFibrin-Thrombin
FibrinolyticFibrinolyticThrombin increasesplatelet aggregationThrombin begets
thrombin
PlateletsActivated by fibrinolytic
Resistance tofibrinolysis PAI-1 Fibrinogen
Primary PCI2003 ESC AMI Guidelines
Evidence Level of Evidence
Recommendations
Class I APreferred treatment if performed by experienced team < 90 min after first medical contact.
Class I CIndicated for patients in shock and those with contraindications to fibrinolytic therapy
Class IClass IIa
AA
GP IIb/IIIa antagonists and primary PCI• no stenting• with stenting
European Heart Journal 2003;24:28-66.
Should the 90 min PCI window be Should the 90 min PCI window be extended?extended?
C o n s is t e n t A b i l i t y o f A b c ix im a b to C a u s e C o n s is t e n t A b i l i t y o f A b c ix im a b to C a u s e D e th r o m b o s is in A M I P a t ie n t sD e th r o m b o s is in A M I P a t ie n t s
D e th r o m b o s isD e th r o m b o s is
0
1 0
2 0
3 0
4 0
5 0
0 2 0 4 0 6 0 8 0 1 0 0
G o ld Z o r m a nG R A P E
T IM I-1 4
% T
IMI 3
Flo
w
*
** R e s u l ts w ith S t r e p to k in a s e f r o m M e ta -A n a ly s is (A H A 1 9 9 8 ; 9 8 : I - 7 8 4 A b s t r a c t N o . 4 1 0 8 )
A D M IR A L
S P E E D
S P E E D (6 0 m in )_C ir c . 2 0 0 0 ; 1 0 1 :2 7 8 8 -9 4 .
T IM I-1 4 (9 0 m in )C ir c . 1 9 9 9 ; 9 9 :2 7 2 0 -3 2 .
G R A P E (4 5 m in )J A C C 1 9 9 9 ; 3 3 :1 5 2 8 -3 2 .
Z o r m a n , e t a l. ( 3 8 m in )A J C 2 0 0 2 ; 9 0 :5 3 3 -3 6 .
A D M IR A L ( 3 6 m in )N E J M 2 0 0 1 ; 3 4 4 :1 8 9 5 -9 0 3 .
G o ld e t a l (1 0 m in )C ir c . 1 9 9 7 ; 9 5 : 1 7 5 5 -5 9 .
T im e to A n g io g r a p h y
30 Day Composite Endpoint Summary in 1° PCI30 Day Composite Endpoint Summary in 1° PCIDeath, MI or Urgent TVR
11.210.5
14.6
6.9
10.5
5.8 5.06.0
4.5 4.5
0
5
10
15
20
% o
f P
atie
nts
No AbciximabAbciximab
48%p = 0.03
52%p = 0.04
52%p = 0.01
30%p = 0.02
JACC 2000;35:915-21.
NEJM 2001;41:1895-03.
Circ 1998;98:734-41.
n = 401 n = 300 n = 2082n = 483ISAR-2 ADMIRAL CADILLAC*RAPPORT
57%p = 0.02
TCT 2002;Oral Pres.
n = 400ACE**
* CADILLAC includes ischemic stroke** ACE includes disabling stroke
High Risk PCI
adapted from NEJM 2002; 346:957-66
NNT ~20
FollowFollow--Up LV Function in Primary PCI TrialsUp LV Function in Primary PCI Trials
NEJM 2002; 346:957-66
Circ 98; 98: 2695-270155.9 57.0
60.562.2 61.1 61.6
50
55
60
65
70
75
80
ISAR-2 ADMIRAL CADILLAC
n = 72 n = 79 n = 151 n = 149 n = 109 n = 116
%
14 days 6 months 7 months
NEJM 2001; 41:1895-03Circ 1999; 98:2695-2601
No AbciximabAbciximab
High Risk PCI
p = 0.003 p = 0.05 p = 0.84
Mortality Outcomes through 1 YearACE
80
85
90
95
100
0 30 60 90 120 150 180 210 240 270 300 330 360
Su
rviv
al (
%)
p=.043
95 ± 2
89 ± 2
Stenting plus Abciximab
Stenting Alone
Time (days)
Dr Antonucci, Oral presentation, AHA 2003
5,6 %
Absolute
Reduction
NNT 18
Cardiogenic Shock Meta-analysis
Clinical Outcomes at 30 Days
43,4
19
1,7
25
35
4
0
10
20
30
40
50
All causeMortality
p<0.0001
Any Bleeding Major Bleeding
p=NSp<0.02
Control (n=226) Abciximab (n=240)
% o
f p
atie
nts
RR 42.4%AR 18.4%
Dr Phil Reid, Oral presentation, ESC 2003
NNT: 5
““Unless or until there are Unless or until there are new data available, we new data available, we should regard catheter-should regard catheter-based reperfusion with based reperfusion with adjunctive abciximab adjunctive abciximab
therapy as the preferred therapy as the preferred reperfusion therapy for reperfusion therapy for
acute MI.”acute MI.”
Topol, Neumann & Montalescot JACC 2003; Topol, Neumann & Montalescot JACC 2003; 42:1886-942:1886-9
Options for “Platelet” Facilitation
• Transfer + PCI – DANAMI 2 / FINESSE
• Lysis + PCI – GRACIA 1, 2
• Early ReoPro + PCI – ADMIRAL / FINESSE
• Early ReoPro Combo +PCI – BRAVE 1 / CARESS / FINESSE
SummarySummary
• Primary PCI with ReoPro remains the gold-standard
• Facilitated PCI strategy is a work in progress
• Pre-hospital/ early ReoPro …more data awaited from FINESSE
• The time-window of Primary PCI may be extended by ReoPro but Phase 3 data needed
• The platelet is pivotal to Prim. PCI outcomes !