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 Collagen Tissue Factor Thrombin Platelet activation Prothrombin ADP TXA 2 Plasma Clotting Process THROMBUS FibrinogenFibrin Platelet aggregation Becker R et al. J Invas Cardiol. 2003;Aug(suppI):1-15 and Narayanan S. Ann Clin Lab Sci. 1999;29: Targets for antithrombotic treatment

GPI and bivalirudin adjunctive antithrombotic to support PCI in addition to DAP + heparin adjunctive antithrombotic to support PCI in addition to DAP + heparin equivalent ischaemia reduction equivalent ischaemia reduction different rates of bleeding, stent thrombosis different rates of bleeding, stent thrombosis

Antithrombotic therapy to support PCI what? antiplatelet ± anticoagulant ± adjuncive what? antiplatelet ± anticoagulant ± adjuncive who? ACS (troponin pos v troponin neg) ± stable who? ACS (troponin pos v troponin neg) ± stable when? pre hospital v hospital when? pre hospital v hospital duration? cath lab only v post procedure infusion duration? cath lab only v post procedure infusion true cost? true cost?

Antithrombotic therapy to support PCI - what? DAP (clopidogrel ASA 300) + heparin DAP (clopidogrel ASA 300) + heparin GPI GPI bivalirudin bivalirudin

Clinical presentation – who? stable stable ACS ACS diabetes – X ISAR-SWEET* no diabetes X NSTE – troponin negative X NSTE – troponin positive √ ISAR REACT-2” STEMI - √ *Circulation 2004:110;3527 ^NEJM 2004:350;232 “JAMA 2006:295;1531 **NEJM 2001:41;1895 ^^NEJM 2002:346;957 ISAR REACT^ ADMIRAL**, CADILLAC^^

Under utilised? Gold standard Gold standard NICE/AHA/ESC NICE/AHA/ESC

Underutilisation? The evidence

GP IIb/IIIa Antagonists Use by Presentation 2007 data: Ludman CCAD

Freeman Hospital

GPI use and non-compliance to NICE Guidelines: Before and after-ISAR-REACT trial Viswanathan G, Zaman A. Guidelines to practice gap in the use of GPI: from ISAR-REACT to over react? J Interv Cardiol (in press) N = 1685

Underutilised - yes

Underutilisation according to national guidelines – why? new era for coronary intervention new era for coronary intervention dual antiplatelet therapy (600mg clopidogrel) dual antiplatelet therapy (600mg clopidogrel) CIAO study – do we need heparin for selected low risk electives? CIAO study – do we need heparin for selected low risk electives? thrombectomy devices –TAPAS study thrombectomy devices –TAPAS study changing milieu for ACS patients (no more salvage PCI ?!) changing milieu for ACS patients (no more salvage PCI ?!)

Antiplatelet therapy in ACS Single Antiplatelet Rx Dual Antiplatelet Rx Higher IPA ASA ASA + Clopidogrel ASA + Prasugrel - 22% - 20% - 19% + 60% + 38% + 32% Reduction in Ischemic Events 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 Vlaar et al.Lancet 2008

PCI in 2009 Paradigm shift in use of adjunctive therapy during PCI due to: effective (oral) antiplatelet therapy effective (oral) antiplatelet therapy changing milieu of ACS presentation changing milieu of ACS presentation effective thrombus aspiration effective thrombus aspiration less thrombogenic equipment less thrombogenic equipment

Conclusion use of adjunctive therapy for PCI (beyond DAP) is evolving use of adjunctive therapy for PCI (beyond DAP) is evolving largely due to increased potency and safety of oral antiplatelets and largely due to increased potency and safety of oral antiplatelets and improved and novel interventional devices improved and novel interventional devices guidelines for antithrombotic use during PCI need updating guidelines for antithrombotic use during PCI need updating GPI and bivalirudin underutilised according to existing guidelines – but, in 2009 and beyond, does it matter? GPI and bivalirudin underutilised according to existing guidelines – but, in 2009 and beyond, does it matter?

Thank you

4.8% 5.2% 8.5% 7.5% 0% 2% 4% 6% 8% 10% UFH pretreatment (n=2,553) No UFH pretreatment (n=1,042) 30-Day Major Bleeding 4.6% 7.2% 5.2% 5.6% 0% 2% 4% 6% 8% 10% UFH pretreatment (n=2,553) No UFH pretreatment (n=1,042) 30-Day MACE Bivalirudin with "provisional" GP IIb/IIIa Heparin + GP IIb/IIIa P int =0.08 P int =0.47 HORIZONS AMI Trial Switching Data UFH pre-procedure was administered to 65.8% of bivalirudin pts and 76.3% of heparin + GPIIb/IIIa pts RR [95%CI]= 0.81 [0.58,1.14] RR [95%CI]= 1.39 [0.85,2.28] RR [95%CI]= 0.57 [0.42,0.77] RR [95%CI]= 0.69 [0.43,1.12]

ACUITY: MI and Major Bleeding UFH/Enoxaparin + GPI vs. Bivalirudin + GPI vs. Bivalirudin Alone P = 0.35P <0.001 Stone GW et al. NEJM 2006;355:

RecommendationsClassLOE Antiplatelet co-therapy Antiplatelet co-therapy aspirin aspirin NSAID and COX-2 selective inhibitors NSAID and COX-2 selective inhibitors clopidogrel loading dose clopidogrel loading dose GPIIb/IIIa antagonist GPIIb/IIIa antagonist abciximab abciximab tirofiban tirofiban eptifibatide eptifibatide Antithrombin co-therapy Antithrombin co-therapy heparin heparin bivalirudin bivalirudin fondaparinux fondaparinux Adjunctive devices Adjunctive devices thrombus aspiration thrombus aspirationIIIIIIIaIIbIIbIIIaIIIIIbBBCABCCBBB Primary PCI: Adjunctive Therapies