Download Michael J. Lipinski, MD, PhD MedStar Washington

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