4/1/2014

4/1/2014
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I have had no financial relationship over the
past 12 months with any commercial
sponsor with a vested interest in this
presentation
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ST Elevation Myocardial
Infarction.
Diagnosis: 12 lead ECGST
Total blockage of blood flow to
an area of the heart
Cardiac muscle death
STEMI Accounts for 3 million
MI’s worldwide/year
NSTEMI is roughly 4 million MI’s
worldwide/yr
2 times more likely if you are
male
Mortality 5-6% while in hospital.
Up to 18% within a year
Treatment: Fibrinolytics or PCI
(percutaneous coronary
intervention)
Tom Babb
PharmD
Avera Heart Hospital
Evaluate dosing and length of therapy for
antiplatelet regimen after STEMI.
 Identify the differences in Bare Metal vs.
Drug Eluting stents and what that means
for anticoagulation
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Anterior Lead
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2 Options= 1 goal
Goal?
 Open occluded coronary vessel
 Time is muscle( Time=cardiac death)
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Options
 Fibrinolytics?
▪ Most commonly used Tenectaplase (TNKase)
▪ Weight based dose
Anterior Lead
▪ Door to drug <30 min
 PCI (Percutaneous coronary intervention)
▪ Door to balloon or stent <90 min
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4/1/2014
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Initiation of oral beta blockers within 24 hours
 Contraindications: HF signs, low CO state, risk of
cardiogenic shock
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Start ACE-inhibitor or ARB within 24 hours
•2 types of stents approved currently in America
• Drug Eluting Types: Zotalimus, everolimus,
paclitaxel, sirolimus, and more
•On Horizon: bioabsorbable stents (approved in
Europe) ? Length of antiplatelet therapy
Drug-eluting stent
Bare metal stent
Restenosis
Thrombis
formation
 ACE-inhibitor for anterior STEMI, HF, EF<40%
 ARB for patients intolerant to ACE-inhibitors.
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Aldosterone antagonist can be added if
EF<40% or symptomatic heart failure
Differences in BMS vs DES
•BMS have 50-70% increased risk of
restenosis
•DES have increased risk of Stent
Thrombosis due to delay in neointimal
coverage (esp. if they stop taking their
antiplatelet)
Antiplatelet Comparisons
Aspirin
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ASPIRIN (indefinite)
GP IIb/IIIa inhibitors
 Abiciximab, Tirofiban, Eptifibatide
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New STEMI guidelines?
Treatment for STEMI
Prasugrel (Effient)
Ticagrelor
(Brilinta)
*Prodrug
Class
NSAID
Thienopyridine
(2nd generation)
Thienopyridine
(3rd generation)
Cyto-pentyl-triazolopyrimidine
Indication
ACS
PCI w/ stent
ASA intolerance/failure
ACS (+ASA)
PCI (+ASA)
ACS treatment in PCI
patients (+ASA)
ACS (+ASA)
Contraindication: >75
yrs, wt <60kg, stroke
history
P2Y12 Inhibitors
 Clopidogrel, Prasugrel, Ticagrelor, and Ticlopidine
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Clopidogrel
(Plavix)
*Prodrug
Dose/Duration
LD: 160-325mg
MD: 81mg daily
LD: 300-600mg
MD: 75 mg daily
LD: 60mg
MD: 10mg
LD: 180mg
MD: 90mg BID
Duration:
Indefinite
Duration:
ACS, BMS, DES: 1 year
Duration:
1 year
Duration:
1 year
MOA
Irreversible COX-1
inhibitor/Thromboxane
2a inhibitor
Irreversible P2Y12 inhibitor
Irreversible P2Y12 inhibitor
Reversibly modifies
P2Y12
Peak Effect
1-3 hours
6 hours (after LD)
4 hours (after LD)
2 hours (after LD)
CYP Metabolism
No
CYP2C19
CYP3A4, CYP2B6
CYP3A4/5
Holding dose prior
to surgery
Continue unless risk of
bleeding outweighs the
risk to stop .
5-7 days
7 days
5 days
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CREDO Study
 2116 patients (BMS)
 Fibrinolytic therapy (Used only if PCI not capable
within 120 minutes) Door to drug <30 minutes
 Plavix and aspirin X 1 yr vs Plavix for 1 month and
▪ 4 baby aspirin and aspirin daily
▪ Plavix 300 mg load if <75 yo or 75mg if >75 yo then 75mg daily
for at least 14 days but preferably one year.
 At 1 yr risk of composite of Death, MI, or stroke
Aspirin indefinitely
was significantly lower in extended plavix arm
8.5%vs 11.5% with RRR 26.9
 PCI treatment (goal to stent placement <90 min)
▪ 4 baby aspirin and aspirin daily
▪ P2Y12 inhibitor load and maintenance dose for 1 yr!
independent on type of stent
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Limitations
 Did not address Stent thrombosis in study
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4/1/2014
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TRITON-TIMI 38 trial (13,608 pts)
 Compared prasugrel to clopidogrel in ACS patients
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with early invasive/conservative approach
 Endpoints: vascular death, MI, stroke
▪ Follow-up was 1 year
 Ticagrelor had lower event rate than clopidogrel
▪ 9.8% vs 11.7% (p-value 0.001)
▪ No difference in major bleeding (p-value 0.43)
▪ Non- CABG related bleeding endpoint rate > ticagrelor: 2.8% vs 2.2%
(p-value 0.03)
▪ Followed for approximately 15 months
 Prasugrel was found to have a lower event rate than
clopidogrel
▪ 9.9% vs. 12.1% (p-value 0.01)
▪ Bleeding endpoint higher with prasugrel 2.4% vs 1.8%
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Limitation:
 Not powered to detect a reduction in the rate of death
PLATO Trial (18,624 pts)
 Compared ticagrelor to clopidogrel for ACS patients treated
undergoing PCI(10,074 pts were non-STEMI)
 Endpoints of CV death, MI, stroke
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Limitation:
 Duration of follow-up was unequal (some events may not be
from CV causes
recorded due to this)
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Contraindicated in patients with history of stroke or
TIA.
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Aspirin Dose must be <100 mg
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Aspirin, P2Y12, and oral anticoagulation(i.e. warfarin/new
anticoagulants?)
5-10% of patients stented will need to be fully anticoagulated
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What is the duration of treatment
recommended for Dual Antiplatelet therapy
after stent placement post-STEMI?
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Bare metal stents have an increased risk for
___________compared to Drug-eluting
Stents?
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What is the Loading dose of Ticagrelor?
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O'Gara PT, Kushner FG, Ascheim DD, et al. 2013 ACCF/AHA Guideline for the Management of ST-Elevation Myocardial
Infarction: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice
Guidelines J Am Coll Cardiol. 2013;61(4):e78-e140. doi:10.1016/j.jacc.2012.11.019
Montalescot G, Wiviott SD, Braunwald E, et al. Prasugrel compared with clopidogrel in patients undergoing percutaneous
coronary intervention for ST-elevation myocardial infarction (TRITON-TIMI 38): double-blind, randomised controlled trial.
Lancet 2009; 373:723.
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 Mechanical valve patient
 A Fib or DVT/PE
 AMI with apical hypokinesis
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A fib
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High risk for bleeding
 CHADS2 should be 2 or greater for triple therapy
 It may be reasonable to stop aspirin and use P2Y12 plus warfarin/new
anticoagulant.
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Newer anticoagulants (indication A.Fib)
 May want to use dabigatran 110 mg dose or apixaban 5 mg dose
 Rivaroxaban did not have lower risk of bleeding in RELY or ROCKET-
AF.
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Remember, time is muscle!!!
 Door to balloon/stent timing (PCI)?
 Door to drug timing (fibrinolytic)?
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Steg PG, James S, Harrington RA, et al. Ticagrelor versus clopidogrel in patients with ST-elevation acute
coronary syndromes intended for reperfusion with primary percutaneous coronary intervention: A Platelet
Inhibition and Patient Outcomes (PLATO) trial subgroup analysis. Circulation 2010; 122:2131.
What dose of aspirin should be used in
conjunction with Ticagrelor?
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Steinhubl SR, Berger PB, Mann JT 3rd, et al. Early and sustained dual oral antiplatelet therapy following
percutaneous coronary intervention: a randomized controlled trial. JAMA 2002; 288:2411.
Spaulding C, Daemen J, Boersma E, et al. A pooled analysis of data comparing sirolimus-eluting stents
with bare-metal stents. N Engl J Med 2007; 356:989.
CAPRIE Steering Committee. A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk
of ischaemic events (CAPRIE). CAPRIE Steering Committee. Lancet 1996; 348:1329.
CURRENT-OASIS 7 Investigators, Mehta SR, Bassand JP, et al. Dose comparisons of clopidogrel and
aspirin in acute coronary syndromes. N Engl J Med 2010; 363:930.
A.
B.
C.
D.
81mg
100mg
162mg
There is a recommended dose?????
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