Glycoprotein IIb/IIIa inhibitors and bivalirudin: under utilised? Azfar Zaman Freeman Hospital
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Transcript Glycoprotein IIb/IIIa inhibitors and bivalirudin: under utilised? Azfar Zaman Freeman Hospital
Glycoprotein IIb/IIIa inhibitors
and bivalirudin: under utilised?
Azfar Zaman
Freeman Hospital
Newcastle-upon-Tyne
Conflicts of interest:
1. received honoraria from:
Eli Lilly, Medicines Company, BMS, Cordis, Boston Scientific, Abbott
2. received research funding from: Medtronic, Cordis, Boston Scientific
Thrombus formation
ADP
Platelet
activation
Platelet
aggregation
Collagen
TXA2
Thrombin
Tissue
Factor
Plasma
Clotting
Process
Fibrinogen
Fibrin
THROMBUS
Prothrombin
Targets for antithrombotic treatment
Becker R et al. J Invas Cardiol. 2003;Aug(suppI):1-15 and
Narayanan S. Ann Clin Lab Sci. 1999;29:275-280.
GPI and bivalirudin
adjunctive antithrombotic to support
PCI in addition to DAP + heparin
equivalent ischaemia reduction
different rates of bleeding, stent
thrombosis
Antithrombotic therapy to support
PCI
what?
who?
when?
duration?
true cost?
antiplatelet ± anticoagulant ± adjuncive
ACS (troponin pos v troponin neg) ± stable
pre hospital v hospital
cath lab only v post procedure infusion
Antithrombotic therapy to support
PCI - what?
DAP (clopidogrel 600 + ASA 300) +
heparin
GPI
bivalirudin
Clinical presentation – who?
stable
diabetes – X ISAR-SWEET*
no diabetes X ISAR REACT^
NSTE – troponin negative X
ACS
*Circulation 2004:110;3527
^NEJM 2004:350;232
“JAMA 2006:295;1531
**NEJM 2001:41;1895
^^NEJM 2002:346;957
NSTE – troponin positive √ ISAR REACT-2”
STEMI - √
ADMIRAL**, CADILLAC^^
Under utilised?
Gold standard
NICE/AHA/ESC
Underutilisation?
The evidence
GP IIb/IIIa Antagonists
Use by Presentation
2007 data: Ludman
PP
CI
NS
TE
MI
UA
ble
2005
2006
2007
Sta
% Procedures
with any GP
IIb/IIIa
blocker
100
90
80
70
60
50
40
30
20
10
0
CCAD
Freeman Hospital 2002-2008
3000
100%
2583
90%
80%
70%
1958
1728
60%
1586
1424
50%
Number
of PCI's
1280
1165
40%
30%
20%
10%
0
0%
2002
2003
2004
2005
2006
2007
2008
% on GPI
GPI use and non-compliance to NICE Guidelines:
Before and after-ISAR-REACT trial
After ISAR REACT
Total
Before ISAR REACT
Elective patients
N = 1685
Elective diabetic
Emergency
0%
20%
40%
60%
Viswanathan G, Zaman A.
Guidelines to practice gap in the use of GPI: from ISAR-REACT to over react?
J Interv Cardiol (in press)
80%
Underutilised - yes
Underutilisation according to national
guidelines – why?
new era for coronary intervention
dual antiplatelet therapy (600mg clopidogrel)
CIAO study – do we need heparin for selected
low risk electives?
thrombectomy devices –TAPAS study
changing milieu for ACS patients (no more
salvage PCI ?!)
Antiplatelet therapy in ACS
ASA
ASA + Clopidogrel
ASA +
Prasugrel
Reduction
in
Ischemic
Events
- 22%
- 20%
- 19%
+ 60%
Placebo
APTC
Single
Antiplatelet Rx
+ 38%
+ 32%
CURE
TRITON-TIMI 38
Dual
Antiplatelet Rx
Higher
IPA
Increase
in
Major
Bleeds
Coronary Interventions Antiplatelets-based
Only (CIAO Study)
JACC 2008;52:1293
TAPAS : Thrombus aspiration
Total mortality at 1 year
Vlaar et al.Lancet 2008
PCI in 2009
Paradigm shift in use of adjunctive therapy during
PCI due to:
effective (oral) antiplatelet therapy
changing milieu of ACS presentation
effective thrombus aspiration
less thrombogenic equipment
Conclusion
use of adjunctive therapy for PCI (beyond DAP) is evolving
largely due to increased potency and safety of oral
antiplatelets and
improved and novel interventional devices
guidelines for antithrombotic use during PCI need updating
GPI and bivalirudin underutilised according to existing
guidelines – but, in 2009 and beyond, does it matter?
Thank you
HORIZONS AMI Trial Switching Data
UFH pre-procedure was administered to 65.8% of
bivalirudin pts and 76.3% of heparin + GPIIb/IIIa pts
30-Day MACE
10%
Pint=0.08
8%
7.2%
5.6%
6%
5.2%
4.6%
4%
2%
RR [95%CI]=
0.81 [0.58,1.14]
RR [95%CI]=
1.39 [0.85,2.28]
0%
30-Day Major Bleeding
Bivalirudin with "provisional" GP IIb/IIIa
Heparin + GP IIb/IIIa
10%
8.5%
Pint=0.47
7.5%
8%
6%
4.8%
5.2%
4%
2%
RR [95%CI]=
0.57 [0.42,0.77]
RR [95%CI]=
0.69 [0.43,1.12]
UFH pretreatment
(n=2,553)
No UFH
pretreatment
(n=1,042)
0%
UFH pretreatment
(n=2,553)
No UFH
pretreatment
(n=1,042)
ACUITY: MI and Major Bleeding
UFH/Enoxaparin + GPI vs. Bivalirudin + GPI vs. Bivalirudin Alone
P = 0.35
P <0.001
Stone GW et al. NEJM 2006;355:2203-16
Primary PCI: Adjunctive Therapies
Recommendations
Antiplatelet co-therapy
• aspirin
• NSAID and COX-2 selective inhibitors
• clopidogrel loading dose
• GPIIb/IIIa antagonist
abciximab
tirofiban
eptifibatide
Antithrombin co-therapy
• heparin
• bivalirudin
• fondaparinux
Adjunctive devices
• thrombus aspiration
Class
LOE
I
III
I
B
B
C
IIa
IIb
IIb
A
B
C
I
IIa
III
C
B
B
IIb
B