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