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Anticoagulation post STEMI: warfarin for
wall motion abnormality in the era of triple
antithrombotics
Jenelle Rogers
VCH-PHC Pharmacy Resident
2009-2010
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Outline
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Objectives
Case
Background
Clinical Question
Review of Literature
Recommendations
Follow-up
Monitoring
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Objectives
• To review the presentation of ST wave elevated
myocardial infarction (STEMI)
• To review the medical management of STEMI
• To review abnormal wall movement (akinesia)
secondary to STEMI
• To evaluate the literature regarding
anticoagulation in a patients with ventricular
akinesia
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Case
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AD- 54 y/o, 140kg male
CC: Chest pain
Presented to Williams Lake Hospital on Oct.18
Social History: 15 pack year smoker, occasional
EtOH (5 drinks/week), no drug use
• NKDA
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History of Present Illness
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Oct.18th
Onset of retrosternal chest pain (8/10) on
exertion, diaphoresis, nausea at 22:55
Presented in ER (Williams Lake) at 23:10
ST elevation of ECG
Troponin 1.0
Diagnosed with anterior STEMI
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Past Medical History
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Dyslipidemia
Obesity (140kg)
Family history CAD (sister had MI at 55)
No medications PTA
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Review of Systems in ER
• Vitals: BP 149/99, T 36, HR 52, RR 18,
O2 97% ORA
• CNS: A/O x 3
• Resp: no cough, breathing regular and unlabored,
normal breath sounds
• CVS: ST wave elevation in V2-V5, Troponin 1.0, S1+
S2 present, no S3/S4, no murmur, minimal pedal edema
• GI: abdomen soft and obese
• Skin: Pink, warm, diaphoresis
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Timeline in William’s Lake
• 22:55- onset of chest pain
• 23:10- presented in ER, given ASA 160mg
• 23:50- went into ventricular fibrillation
-defibrillated
-epinephrine 1mg iv given x2
• 23:52- normal sinus rhythm
• 00:02- TNK 50mg iv + enoxaparin 30mg iv
• 00:14- amiodarone infusion started @ 90mg/hr
• 00:41-NTG infusion started @ 30mg/hr
• 00:50- CP and ST elevation resolved (50% on ECG)
• Transferred to SPH the following day
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Medications at SPH (Oct 19)
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UFH infusion standard protocol
Nitroglycerin infusion
Amiodarone infusion
ASA 325mg daily
Clopidogrel 75mg daily
Ramipril 2.5mg bid
Metoprolol 25mg bid
Simvastatin 40mg daily
Nicotine 21mg patch daily
Eptifibatide (Integrelin) infusion x 18 hours (Oct.20)
Warfarin 10mg daily (started Oct.21)
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Diagnostics
• 100% occlusion LAD
• 20% occlusion RCA
• 20% occlusion LCX
• Bare metal stent to LAD
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Drug Related Problems
• AD is at risk of a major bleed secondary to
receiving warfarin, clopidogrel and aspirin
and would benefit from reassessment of the
indication of warfarin
• AD is at risk of hypotension secondary to
receiving metoprolol, ramipril and nitro patch.
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STEMI: Background
• Full occlusion of coronary artery
• Signs and symptoms:
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Retrosternal chest pain
SOB
N/V
Diaphoresis
• Diagnostics
– ST elevation >0.1mv in 2 (or more) contiguous pericardial leads (V1 –
V6) or 2 (or more) adjacent limb leads
– New left bundle branch block (LBBB) on ECG
– CP
• Prolonged ischemia can cause regional abnormalities of heart
wall movement
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Ventricle Wall Motion Abnormalities
• Definitions
Hypokinesis- decreased systolic inward motion
Akinesis- no systolic inward motion
Dyskinesis- outward systolic bulging
• Diagnosis: ECHO
• Concern: akinesis (particularly in the apex) can
increase the risk of thrombus formation and
stroke
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STEMI: Treatment
• Class I recommendation:
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Reperfusion (PCI or fibrinolytic)
UFH
ASA
Clopidogrel
Beta blocker
ACE inhibitor
Nitroglycerin for ongoing chest pain
Morphine
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STEMI: Treatment
Class I recommendation:
– Warfarin
STEMI patients who have a cardiac source of embolism
(atrial fibrillation, mural thrombus, or akinetic segment)
should receive moderate-intensity (INR 2 to 3) warfarin
therapy (in addition to aspirin). The duration of warfarin
therapy should be dictated by clinical circumstances (eg, at
least 3 months for patients with an LV mural thrombus or
akinetic segment and indefinitely in patients with persistent
atrial fibrillation). The patient should receive LMWH or
UFH until adequately anticoagulated with warfarin. (Level of
Evidence: B)
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STEMI: Treatment
Class IIa recommendation
– Warfarin
It is reasonable to prescribe warfarin to post-STEMI
patients with LV dysfunction and extensive regional
wall-motion abnormalities. (Level of Evidence: A)
– LMWH
– Glycoprotein IIb/IIIa inhibitor
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Clinical Question
• In patients with wall motion abnormalities post
STEMI, would the benefits of a prophylactic
course of warfarin therapy outweigh the risks in
terms of death, stroke, and bleeding when
compared to placebo?
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Search Strategy
• Databases: Pubmed, Embase
• Search terms: warfarin or vitamin k antagonist,
myocardial infarction, akinesis
• Results:
– None
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Approach
• No evidence, but still have to answer clinical
question
• Try to extrapolate efficacy and toxicity of
warfarin for this indication from available data
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Efficacy of warfarin
• Broadened search criteria to include patients
without abnormal wall motion and with left
ventricular thrombi present
• Results
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Meta-analysis: 0
RCT: 1
Retrospective review: 1
Case reports: 2
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Left ventricular thrombi after short-term
high-dose anticoagulants in acute
myocardial infarction
Johannessen et al.
Euro Heart Journal. 1987;8:975-80
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Johannessen et al.
• Randomized controlled trial
• 42 patients with anterior wall MI
– 21 patients received 10 days anticoagulation (UFH
 warfarin)
– 21 patients received 10 days placebo
• Patients were not given any anti-platelet
therapy
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Johannessen et al.
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Johannessen et al.
Outcome
(within 6
months)
Stroke*
Non fatal
re-infarction
Death
Bleeding
Group 1
(placebo)
2
2
6
0
Group 2
(10 days
warfarin)
1
2
0
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P value
NSS
NSS
0.01
NSS
• *1 patient from each group 1 and 2 had thrombus at one month and was
receiving warfarin when the stroke occurred (at 6 and 8 weeks)
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Quoted in the ACC/AHA Guidelines
Study
Method
WARIS II:
ASA
vs. ASA +
warfarin
APRICOT II:
ASA
vs. ASA +
warfarin
Primary
Endpoint
Result
3630 pts,
<75 years
randomized, multi
with acute
center, open-label, 4 STEMI
year follow
up
Death, nonfatal
reinfarction, or
thromboembolic
cerebral stroke
Primary
endpoint:
24.55 vs.
17.4% (p=0.0005)
Major bleed:
0.17% vs.
0.68% (p=0.001)
308 pts,
randomized, multi
center, open-label, 3
month follow up
Reocclusion of
the
infarct related
artery at
angiographic
follow-up
Primary
endpoint:
28% vs.
15% (p=0.02)
Major bleed:
NSS (1.5%
in both groups)
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Patient
Population
<75 years
with acute
STEMI
treated with
fibrinolysis
Risk of Major Bleed
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Risk of Major Bleed with TT
Study
Design
ManzanoFernandez
(2008)
Retrospective
cohort
Rogacka
(2008)
Retrospective
cohort
Patients and Tx
AF for PCI
Major Bleed
21.6% vs 3.8%
(p=0.006)
TT use, baseline
anemia were
predictors of
late major bleed
5.6 vs 3.6%
(p=1.0)
Follow-up
21mon
6.6% vs 0%
(p=0.014)
Follow-up
~220d
TT (n=51) vs nonTT (n=53)
AF & other
indication for PCI
Comments
TT (n=71) vs
DAPT (n=56)
Khurram
(2006)
Retrospective
Cohort
AF, LV thrombus
for PCI
TT (n=107) vs
DAPT (n=107)
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Risk of Major Bleed with TT
Study
Nguyen
(2007)
Design
Retrospective
cohort
Patients and Tx
ACS with PCI
Major Bleed
5.9% vs 4.6%
(p=0.46)
Comments
In-hospital
bleed only
TT (n=580) vs
DAPT (n=220)
Ruiz-Nodar
(2008)
Retrospective
cohort
AF undergoing PCI 14.9% vs 9.0%
(p=0.19)
2 yr follow-up
TT (n=213) vs
DAPT (n=174)
Sarafoff
(2009)
Prospective
cohort
AF undergoing PCI 3.1% vs. 1.4%
(p=0.34)
TT (n=306) vs
DAPT (n=209)
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2 yr follow-up
Risk of Major bleed with TT
Study
Mattichak
(2005)
Design
Retrospective
cohort
Patients & Tx
Major
Bleeding
Comments
LV thrombus, AF for 15% vs 0% GI 12 mon follow-up
PCI
Bleed (p=NS)
TT (n=40) vs
DAPT (n=42)
21% vs 3.5%
transfusion
(p=0.028)
Konstantino
(2006)
Retrospective
cohort
TT (n=76) vs
DAPT (n=2661)
2.6% vs. 0.6%
(p=0.03)
Anand
(2007)
Prospective,
randomized
PAD
4% vs. 1.2%
Life-threatening
(p<0.001); RR bleed
3.41
Follow-up 2.5-3.5
yr
WAVE
Study
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TT (n=1080) vs
DAPT (n=1081)
AC indication
unknown
Considerations
• Benefit of prophylactic warfarin = ?
• Risk of major bleed with
– ASA: ~1.2% per year
– ASA + clopidogrel: ~2-3% per year
– ASA + clopidogrel + warfarin: up to 21% per year
• Target INR = ?
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Considerations
• 1996 ACC/AHA guidelines:
“The previous ACC/AHA guidelines strongly recommended
the use of oral anticoagulants with an INR of 2.0 to 3.0 in
patients with a ventricular mural thrombus or large akinetic
region of the left ventricle for at least 3 months. Despite a
number of small observational studies demonstrating a higher
risk of embolic stroke in patients treated with large anterior
infarction and a better outcome with warfarin after
demonstration of LV mural thombus by echocardiography,
randomized controlled trials are not available to support
this recommendation.”
• When this recommendation was initiated, patients were not
receiving dual antiplatelets
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Recommendations
• Recommend D/C warfarin
• Discharge patient on:
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Clopidogrel x 1 month
ASA
Metoprolol
Ramipril
Simvastatin
Nicotine patch
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Follow up
• Physician declined recommendation and
continued with warfarin x 3 months
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Monitoring
Parameter
INR
When
Daily until therapeutic Laboratory
Bleeding/Bruising Daily
Warfarin D/C
Compliance
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Who
Pt
Three months
Dr
Prescription refills
Pharmacist
References
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A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to
Revise the 1999 Guidelines for the Management of Patients With Acute Myocardial Infarction). ACC/AHA Guidelines for the
Management of Patients With ST-Elevation Myocardial Infarction. Circulation. 2004;110:588-636.
2007 Focused Update of the ACC/AHA 2004 Guidelines for the Management of Patients With ST-Elevation Myocardial
Infarction: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines.
Johannessen K, Nordreghaug J, Lippe G. Left ventricular thrombi after short-term high-dose anticoagulants in acute myocardial
infarction. Eur Heart Journal. 1987;8:975-80.
Porter A, Kandalker H, Iakobishvili Z, Sagie A et al. Left ventricular thrombus after anterior ST-segment elevation acute
myocardial infarction in the era of aggressive reperfusion therapy – still a frequent complication. Coron Art Dis
2005;16(5):275-79
Fitzmaurice D, Blann A, Lip G. Bleeding risks of antithrombotic therapy BMJ. 2002; 325(7368): 828–831.
Hurlen M, Abdelnoo M, Smith P, Erikssen J, Arnesen H. Warfarin, Aspirin, or Both after Myocardial Infarction. NEJM.
2002;347:969-974
Brouwer MA, van den Bergh PJ, Aengevaeren WR, et al. Aspirin plus coumarin versus aspirin alone in the prevention of
reocclusion after fibrinolysis for acute myocardial infarction: results of the Antithrombotics in the Prevention of Reocclusion In
Coronary Thrombolysis (APRICOT)-2 Trial. Circulation 2002;106:659-65.
Zinn A, Feit F. Optimizing antithrombotic strategies in patients with concomitant indications for warfarin undergoing coronary
artery stenting. AJC. 2009;104(5):49C-54C.
Hermosillo J, Spinler S et al. Aspirin, Clopidogrel and Warfarin: Is the Conbination Appropriate and Effective or Innappropriate
and Too Dangerous. Ann of Pharm. 2008;42:790-805.
Schomig A, Sarafoff N, Seyfarth M. Triple antithrombotic management after stent implantaion: when and how? Heart.
2009;95:1280-85.
Active A Investigators, Connoly S, Pogue J, Hart R et al. Effect of clopidogrel added to aspirin in patients with atrial
fibrillation. NEJM. 2009;360(20):2066-78.
A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on
Management of Acute Myocardial Infarction). ACC/AHA Guidelines for the Management of Patients With ST-Elevation
Myocardial Infarction. JACC. 1996;28(5):1328-428.
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