Anticoagulation in STEMI Marc Cohen MD FACC Chair

Anticoagulation in STEMI Marc Cohen, MD, FACC Chair, Dept. of Medicine Formerly, Director Division of Cardiology Newark Beth Israel Medical Center, NJ Professor of Medicine Rutgers – New Jersey Medical School

Marc Cohen, MD, FACC has the following relationships that might materially affect this presentation Grant/Research Support: Janssen, Astra. Zeneca Advisory Board/Consultant: Sanofi, Maquet, Astra. Zeneca, Janssen Speakers Bureau: Janssen, BI, AZ, Novartis, Amgen Major Stock Shareholder: NONE

Antithrombins AT C IIa S Hep UFH Direct antithrombin Xa Otamixaban (iv) AT Xa LMWH AT Xa Pentasaccharide

UFH: Relationship between ACT levels and outcomes

Heparin + GP 2 b 3 a blockade vs. Bivalirudin monotherapy HORIZONS: Stone et al, NEJM 2008; 358: 2218 Primary Outcome Measures (ITT) *Not related to CABG **MACE = All cause death, reinfarction, ischemic TVR or stroke

HORIZONS: Acute Stent Thrombosis: Impact of Pre-Randomization Heparin Def/Prob Stent Thrombosis (%) 3. 5 No Pre-Randomization Heparin 3. 0 Bivalirudin 2. 6% 2. 5 HR = 3. 07 [1. 33, 7. 09] P = 0. 006 2. 0 1. 5 Pre-Randomization Heparin 1. 0 Bivalirudin 0. 9% UFH+GPI HR [95%CI] = 9. 64 [1. 00, 92. 70] 0. 5 P = 0. 02 UFH+GPI 0. 1% 0. 0 0 Number at risk P-R Heparin 1066 545 6 12 18 24 1050 528 1049 528 Time in Hours 1052 531 1051 529 0. 8%

STEMI Prim PCI 11. 3% 6. 7% ENOXAPARIN 0. 5 mg/kg/iv vs UFH Montalescot et al, Lancet 2011

Changing Landscape for PCI in ACS 1. Large fraction of patients now being treated with potent P 2 Y 12 -inhibitors. 2. >90% of procedures use radial artery access. 3. No planned GPI treatment. VALIDATE-SWEDEHEART trial and substudies

Bivalirudin Started during Transport for Primary PCI: Steg PG, et al; EUROMAX NEJM 2013 No difference in mortality 60% GP 2 b 3 a Radial 48% there was a higher risk of acute stent thrombosis with bivalirudin, neither a prolonged, reduced-dose infusion of bivalirudin nor the new oral P 2 Y 12 inhibitors was sufficient to address this risk.

ACT in NSTEMI: TAO Sub-study MATRIX; NEJM 2015 No significant relationship between last ACT value before PCI and ischemic outcomes Hintrelationship of lower Cardio. V No significant between peak ACTMortality and bleeding outcomes

Bivalirudin vs. Heparin in MI: VALIDATE SWEDEHEART Radial access 90% GP 2 b 3 a 0% Planned MATRIX Antithrombin No diff in Mortality, Bleeding No significant relationship between last ACT value before PCI and ischemic outcomes No significant relationship between peak ACT and bleeding outcomes More Definite ST with Bival

Steg PG. , JAMA 2013; Otamixaban iv anti-Xa inhibitor

PCI in AMI: with Potent P 2 Y 12 inhibitors: Ideal ACT? ? VALIDATE-SWEDEHEART No planned GP IIb/IIIa use No significant association between ACT and clinical outcomes!! Sharma et al, Eur Heart J Cardiovasc Pharmacother 2019

UFH Less TIMI grade 5 thrombus in pretreatment arm (60. 5% vs. 71. 6%). No difference in ischemic end points !! No significant association between ACT and clinical outcomes!! Cantor et al, Catheter Cardiovasc Interv. 2019

Anticoagulants in STEMI; Summary Fondaparinux: • Useful in NSTEMI • Not approved in US because of complications during Primary PCI Enoxaparin • Effective in ATOLL trial but did NOT reach superiority to UFH Bivalirudin • Superior safety with bleeding but consistently more stent thrombosis • More recent Euromax trial No mortality advantage Unfractionated Heparin: The Old Dog in the current era • Widely used despite limitations; Pre-treatment better • and NO agreed upon ACT target