Ticagrelor and Eptifibatide Bolus Versus 2-H Infusion in High-Risk NSTEMI Patients

Ticagrelor and Eptifibatide Bolus Versus 2-h Infusion in High-Risk NSTEMI Patients

Massoud Leesar, MD Professor of Medicine Section head-Interventional Cardiology University of Alabama, Birmingham disclosure Massoud Leesar, MD

AstraZeneca: Research Support Background • In patients with NSTEMI undergoing ad hoc PCI, inhibition of platelet aggregation (IPA) with a potent P2Y12 inhibitor, ticagrelor, was inferior to glycoprotein IIb/IIIa inhibitors (GPI) infusion at 2 hours, the time frame in which the majority of patients undergo PCI • Standard GPI infusion (12-14 h) increased the risk of bleeding. GPI bolus or bolus + 2 h infusion immediately inhibited platelet aggregation and reduced the risk of bleeding Background (cont’ed) • A number of randomized trials showed that early or immediate PCI reduced event rates in high-risk NSTE-ACS patients • The effects of ticagrelor and eptifibatide bolus versus eptifibatide bolus+ 2 h infusion on inhibition of platelet aggregation and platelet reactivity (HPR) in high-risk NSTEMI patients undergoing early PCI in is unknown Primary end-point: IPA at 2 h

Marian et al. J Am Heart Assoc. 2017;6:e005562. Definitions • High on-treatment platelet reactivity (HPR) is defined as platelet aggregation >59% in response to ADP 20 µm/L • Adenosine diphosphate (ADP) is an agonist binds to

P2Y12 receptors on platelet surface and inhibited by P2Y12 receptor inhibitors • Thrombin-receptor activating peptide (TRAP) is an agonist binds to fibrinogen or PAR receptors on platelet surface and inhibited by GPI • Periprocedural MI defined as (>5 x 99th percentiles or >20%increase in troponin levels) Marian et al. J Am Heart Assoc. 2017;6:e005562 Marian et al. J Am Heart Assoc. 2017;6:e005562 Marian et al. J Am Heart Assoc. 2017;6:e005562 The incidence of peri-procedural MI

20 EPT bolus+TIC

15 EPT bolus+2 h % infusion+TIC 10

0 PMI Marian et al. J Am Heart Assoc. 2017;6:e005562. Post-procedure Hb levels

EPT bolus+TIC EPT bolus+2h inusion+TIC 15 14 13 g/dL 12 11 10 Post- procedure Hb Levles Marian et al. J Am Heart Assoc. 2017;6:e005562 12-month event rates

5 4.5 4 3.5 3 EPT bolus+TIC 2.5 EPT bolus+2h infusion+TIC % 2 1.5 1 0.5 0 Bleeding Death TLR NSTEMI

Marian et al. J Am Heart Assoc. 2017;6:e005562 Conclusions • IPA with ticagrelor and eptifibatide bolus was maximal at 2 hours, suggesting that eptifibatide 2-hour infusion is not needed • ticagrelor + eptifibatide bolus maximally inhibited HPR in all patients, which was below the cut point associated with ischemic risk • Eptifibatide bolus or 2-h infusion had bridging effect and inhibited platelet aggregation during the first 6 h until the full IPA by ticagrelor to take place • Future randomized trials are needed to investigate the safety and efficacy of ticagrelor + eptifibatide bolus vs. cangrelor in high-risk ACS patients undergoing early PCI

TIMACS Tim ing of Intervention in patients with Acute Coronary S yndromes

An International Randomized Trial of Early Versus Delayed Invasive Strategies in Patients with Non-ST Segment Elevation Acute Coronary Syndromes

Mehta et al. N Engl J Med 2009;360:2165-75

TIMACS trial May 2009 N Engl J Med 2009;360:2165-75.

The RIDDLE-NSTEMI Study

< 2 h 2 -72 h

Milosevic et al. JACC Intv 2016 Milosevic et al. JACC Intv 2016

Definitions • High on-treatment platelet reactivity (HPR) is defined as platelet aggregation >59% in response to ADP 20 µm/L • Adenosine diphosphate (ADP) as an agonist binds to

P2Y12 receptors on platelet surface • Thrombin-receptor activating peptide (TRAP), as an agonist binds to fibrinogen or PAR receptors on platelet surface • Periprocedural MI defined as (>5 x 99th percentiles or >20%increase in troponin levels) SNPs of CYP2C19 gene and prevalence of genetically predicted metabolizers in different ethnicities