Glycoprotein IIb/IIIa inhibitors and bivalirudin: under utilised?

1
Glycoprotein IIb/IIIa inhibitors and bivalirudin
under utilised?

• Azfar Zaman
• Freeman Hospital
• Newcastle-upon-Tyne

2
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
3
Thrombus formation
Targets for antithrombotic treatment
Becker R et al. J Invas Cardiol.
2003Aug(suppI)1-15 and Narayanan S. Ann Clin
Lab Sci. 199929275-280.
4
GPI and bivalirudin

• adjunctive antithrombotic to support PCI in
  addition to DAP heparin
• equivalent ischaemia reduction
• different rates of bleeding, stent thrombosis

5
Antithrombotic therapy to support PCI

• what? antiplatelet anticoagulant adjuncive
• who? ACS (troponin pos v troponin neg) stable
• when? pre hospital v hospital
• duration? cath lab only v post procedure infusion
• true cost?

6
Antithrombotic therapy to support PCI - what?

• DAP (clopidogrel 600 ASA 300) heparin
• GPI
• bivalirudin

7
Clinical presentation who?

• stable
• ACS

diabetes X ISAR-SWEET
ISAR REACT
no diabetes X
NSTE troponin negative X
NSTE troponin positive v ISAR REACT-2
Circulation 20041103527 NEJM
2004350232 JAMA 20062951531 NEJM
2001411895 NEJM 2002346957
STEMI - v
ADMIRAL, CADILLAC
8
Under utilised?

• Gold standard
• NICE/AHA/ESC

9
(No Transcript)
10
Underutilisation?

• The evidence

11
GP IIb/IIIa AntagonistsUse by Presentation
CCAD
12
Freeman Hospital 2002-2008
13
GPI use and non-compliance to NICE Guidelines
Before and after-ISAR-REACT trial
N 1685
Viswanathan G, Zaman A. Guidelines to practice
gap in the use of GPI from ISAR-REACT to over
react? J Interv Cardiol (in press)
14
Underutilised - yes
15
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 ?!)

16
Antiplatelet therapy in ACS
ASA
ASA Clopidogrel
ASA Prasugrel
Reduction inIschemicEvents
- 22
- 20
- 19
Increase in Major Bleeds
32
38
60
Single Antiplatelet Rx
Dual Antiplatelet Rx
Higher IPA
17
Coronary Interventions Antiplatelets-based Only
(CIAO Study)
JACC 2008521293
18
TAPAS Thrombus aspirationTotal mortality at 1
year
Vlaar et al.Lancet 2008
19
(No Transcript)
20
(No Transcript)
21
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

22
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?

23
Thank you
24
HORIZONS AMI Trial Switching Data
UFH pre-procedure was administered to 65.8 of
bivalirudin pts and 76.3 of heparin
GPIIb/IIIa pts
Bivalirudin with "provisional" GP IIb/IIIa
Heparin GP IIb/IIIa
Pint0.47
10
10
Pint0.08
8.5
7.5
8
7.2
8
5.6
5.2
5.2
6
6
4.8
4.6
30-Day Major Bleeding
30-Day MACE
4
4
2
2
RR 95CI 0.81 0.58,1.14
RR 95CI 1.39 0.85,2.28
RR 95CI 0.57 0.42,0.77
RR 95CI 0.69 0.43,1.12
0
0
UFH pretreatment
No UFH
UFH pretreatment
No UFH
(n2,553)
pretreatment
(n2,553)
pretreatment
(n1,042)
(n1,042)
25
ACUITY MI and Major Bleeding
UFH/Enoxaparin GPI vs. Bivalirudin GPI vs.
Bivalirudin Alone
P 0.35
P lt0.001
Stone GW et al. NEJM 20063552203-16
26
Primary PCI Adjunctive Therapies