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Pharmacotherapy Update for STEMI: What Is New? Michael J. Lipinski, MD, PhD MedStar Washington Hospital Center Michael J. Lipinski, MD, PhD Medicure Inc: Research grant and consulting STEMI: The Epidemiological Impact • Half of individuals present with unheralded AMI or SCD as their first manifestation of CAD • Approximately 500,000 STEMI per year in the US • Adverse outcomes remain high (4.7% In-hospital mortality and 9.0% at 1 year) Montalescot, EHJ 2007 • While we have reduced mortality, many of these patients develop heart failure The Pefect STEMI • A patient with no medical problems calls 911 immediately after onset of chest pain and decides to chew aspirin 325 mg at that time. • EMS arrives, rapidly transports the patient to the PCI-capable hospital down the street and performs an ECG en route. • In the ED, patient has an IV placed, takes an rapid-onset oral P2Y12 inhibitor, and heads to the cath lab • The interventionalist explains the risks/benefits of PCI as the patient is draped and the procedure begins. • You make the perfect stick, anticoagulation is started, you rapidly perform angiography, wire a thrombotic 90% stenosis, and perform direct stenting. • Door to stent time was 30 minutes, but your oral P2Y12 inhibitor won’t kick in for over an hour!!! Example STEMI • 64 y/o female with HTN and HLD presents to the ED for chest pain and ECG shows inferior STEMI. • IV Heparin bolus, morphine 2mg IV, ASA 324 mg, and Ticagrelor 180 mg given in the ED but vomited going to the lab. The Problem with MONA • Aspirin is really the only good thing. • When 324 mg vs 81 mg? • Oxygen was recently shown not to help unless hypoxic. • Nitro is bad for RV involvement. • Morphine slows uptake of oral P2Y12 inhibitor. Kubica, Eur Heart J, 2015 Pharmacotherapy for PCI • The Ideal: – Immediate anticoagulation and platelet inhibition to minimize ischemic events. – No increase in bleeding risk. • Anti-platelet coverage to enable time for oral P2Y12 inhibitor to take effect. • Can glycoprotein IIb/IIIa inhibitors (GPI) or cangrelor fill this roll? Rapid Platelet Inhibition with GPI Onset of Oral P2Y12 Inhibition GP IIb/IIIa Inhibitors • Only to be used on the way to the cath lab or in the cath lab • Good for large thrombus burden, complex PCI, inadequate antiplatelet therapy. • Is there a contraindication? – – – – – Recent surgery Prior major GI bleed or ICH Prior stroke Thrombocytopenia Great caution with use after thrombolytic therapy • Abciximab: – monoclonal antibody blocking fibinogen and GP receptor – Prolonged platelet inhibition • Tirofiban and Eptifibatide: – small molecule GPIs – Cleared relatively quickly (3 hour half-life) – Requires renal dosing • Meta-analysis shows greater bleeding risk but less MACE What About Cangrelor?? • Rapid-onset, intravenous, rapidly-reversible P2Y12 inhibitor • Half-life is 3 to 5 minutes • Ticagrelor can be given concomitantly • Must wait to load with clopidogrel or prasugrel until after PCI – Big problem if patient is already loaded • Ideal if concern for surgical disease (rapid off-set) • Major drawback is the cost Anticoagulation prior to the Lab • Fondaparinux is an option, though not often used (Messy in the lab) • Bivalirudin or Argatroban for patients with HIT (Unsure there is benefit) • If going directly to the cath lab, either UFH or nothing at all • Lovenox has been shown to be superior to UFH in NSTEMI for ACS Heparin in the Lab • UFH bolus (70 units/kg) but most don’t give too much above 5000 units IV. • Data with larger boluses (100 units/kg) just associated with greater bleeding. • Ideal ACT between 250-300 for heparin without GP IIb/IIIa inhibitor. • When using GP IIb/IIIa inhibitor, ACT should be between 200-250 to prevent increased bleeding. • UFH redosing often based on estimates (ACT from initial bolus and drop during case) • Many operators are very particular regarding sheath pulls/closure based on pharmacology Bivalirudin (Angiomax) • Set it and forget it!!?? • Specific and reversible direct thrombin inhibitor • Cleared by kidneys and proteolytic cleavage so renal dosed in bad CKD/ARF • No risk for HITT • Half-life is 25 minutes • Dosing: Bolus 0.75 mg/kg, Infusion 1.75 mg/kg/h • Check ACT after initial bolus. If ACT<300, I give a 1/3 dose re-bolus • GP IIb/IIIa inhibitors should be used provisionally (aka bailout) Bivalirudin vs UFH • Cost is a real issue. Bivalirudin is much more expensive. • Bivalirudin significantly decreases bleeding risk by 40% (both access and non-access site bleeding) • Bivalirudin associated with 60% increase in early stent thrombosis • Initial heparin bolus in the ER and prolonged PCIdosed infusion of Angiomax shown to mitigate risk of acute ST • Consider access (radial vs femoral). MATRIX trial and EuroMAX are important reads • Also, assess thrombus burden!! If you are going to use a GPI, I would pick heparin. Oral P2Y12 Inhibitors: Clopidogrel • Member of thienopyridine family which is an irreversible ADP receptor inhibitor • Requires 2 steps to be activated in the liver • 600 mg Loading dose faster than 300 mg and shown to be better for MACE • If no loading dose, therapeutic in 4 to 6 days!! • Compliance and cost are a big driver for choosing this med Oral P2Y12 Inhibitors: Prasugrel • Member of thienopyridine family which is an irreversible ADP receptor inhibitor • Requires a single step for activation in the liver • Rapid onset of action and achieves much greater platelet inhibition than clopidogrel • TRITON-TIMI trial showed superior to clopidogrel • Old small people with stroke – Contraindications: prior stroke/TIA, age >75, <60 kg – Surgery is a big problem (7 days) and greater bleeding Oral P2Y12 Inhibitors: Ticagrelor • • • • • • • • Reversible direct oral P2Y12 inhibitor Major efficacy trial in ACS was PLATO Comparison in STEMI and NSTEMI Superior to Clopidogrel Rapid Onset No difference in CABG-related bleeding Greater minor bleeding Adenosine-mediated effects (SOB, HF, Asthma, Bradycardia) STEMI: Current Optimal Medical Therapy • Aspirin 325 mg immediately • Immediate loading with oral P2Y12 inhibitor (preference for ticagrelor or prasugrel) • Emergent Revascularization with heparin or bivalirudin for anticoagulation • Consider IV platelet inhibition with GP IIb/IIIa inhibitor or cangrelor • Early initiation of beta-blocker • Addition of renin-angiotensin-aldosterone system blockade • Early initiation of statin therapy Conclusions • There are a variety of potential new therapies to treat pts with STEMI • Studies are needed to better clarify the utility of IV anti-platelet medications in the cath lab • Heparin reduces thrombotic events while bivalirudin reduces bleeding • Loading with oral antiplatelet agents should occur before leaving the lab