Anticoagulation post STEMI: warfarin for wall motion abnormality in the era of triple antithrombotics

1
Anticoagulation post STEMI warfarin for wall
motion abnormality in the era of triple
antithrombotics

• Jenelle Rogers
• VCH-PHC Pharmacy Resident
• 2009-2010

2
Outline

• Objectives
• Case
• Background
• Clinical Question
• Review of Literature
• Recommendations
• Follow-up
• Monitoring

3
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

4
Case

• 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

5
History of Present Illness

• Oct.18th
• Onset of retrosternal chest pain (8/10) on
  exertion, diaphoresis, nausea at 2255
• Presented in ER (Williams Lake) at 2310
• ST elevation of ECG
• Troponin 1.0
• Diagnosed with anterior STEMI

6
Past Medical History

• Dyslipidemia
• Obesity (140kg)
• Family history CAD (sister had MI at 55)
• No medications PTA

7
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

8
Timeline in Williams Lake

• 2255- onset of chest pain
• 2310- presented in ER, given ASA 160mg
• 2350- went into ventricular fibrillation
• -defibrillated
• -epinephrine 1mg iv given x2
• 2352- normal sinus rhythm
• 0002- TNK 50mg iv enoxaparin 30mg iv
• 0014- amiodarone infusion started _at_ 90mg/hr
• 0041-NTG infusion started _at_ 30mg/hr
• 0050- CP and ST elevation resolved (50 on ECG)
• Transferred to SPH the following day

9
Medications at SPH (Oct 19)

• 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)

10
Diagnostics

• 100 occlusion LAD
• 20 occlusion RCA
• 20 occlusion LCX
• Bare metal stent to LAD

11
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.

12
STEMI Background

• Full occlusion of coronary artery
• Signs and symptoms
• Retrosternal chest pain
• SOB
• N/V
• Diaphoresis
• Diagnostics
• ST elevation gt0.1mv 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

13
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

14
STEMI Treatment

• Class I recommendation
• Reperfusion (PCI or fibrinolytic)
• UFH
• ASA
• Clopidogrel
• Beta blocker
• ACE inhibitor
• Nitroglycerin for ongoing chest pain
• Morphine

15
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?

18
Search Strategy

• Databases Pubmed, Embase
• Search terms warfarin or vitamin k antagonist,
  myocardial infarction, akinesis
• Results
• None

19
Approach

• No evidence, but still have to answer clinical
  question
• Try to extrapolate efficacy and toxicity of
  warfarin for this indication from available data

20
Efficacy of warfarin

• Broadened search criteria to include patients
  without abnormal wall motion and with left
  ventricular thrombi present
• Results
• Meta-analysis 0
• RCT 1
• Retrospective review 1
• Case reports 2

21
Left ventricular thrombi after short-term
high-dose anticoagulants in acute myocardial
infarction

• Johannessen et al.
• Euro Heart Journal. 19878975-80

22
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.
24
Johannessen et al.

• 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)

Outcome (within 6 months) Group 1 (placebo) Group 2 (10 days warfarin) P value
Stroke 2 1 NSS
Non fatal re-infarction 2 2 NSS
Death 6 0 0.01
Bleeding 0 0 NSS
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Quoted in the ACC/AHA Guidelines
Study Method Patient Population Primary Endpoint Result
WARIS II ASA vs. ASA warfarin 3630 pts, randomized, multi center, open-label, 4 year follow up lt75 years with acute STEMI Death, nonfatal reinfarction, or thromboembolic cerebral stroke Primary endpoint 24.55 vs. 17.4 (p0.0005) Major bleed 0.17 vs. 0.68 (p0.001)
APRICOT II ASA vs. ASA warfarin 308 pts, randomized, multi center, open-label, 3 month follow up lt75 years with acute STEMI treated with fibrinolysis Reocclusion of the infarct related artery at angiographic follow-up Primary endpoint 28 vs. 15 (p0.02) Major bleed NSS (1.5 in both groups)
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Risk of Major Bleed
27

Risk of Major Bleed with TT
Study Design Patients and Tx Major Bleed Comments
Manzano-Fernandez (2008) Retrospective cohort AF for PCI TT (n51) vs non-TT (n53) 21.6 vs 3.8 (p0.006) TT use, baseline anemia were predictors of late major bleed
Rogacka (2008) Retrospective cohort AF other indication for PCI TT (n71) vs DAPT (n56) 5.6 vs 3.6 (p1.0) Follow-up 21mon
Khurram (2006) Retrospective Cohort AF, LV thrombus for PCI TT (n107) vs DAPT (n107) 6.6 vs 0 (p0.014) Follow-up 220d
28

Risk of Major Bleed with TT

Study Design Patients and Tx Major Bleed Comments
Nguyen (2007) Retrospective cohort ACS with PCI TT (n580) vs DAPT (n220) 5.9 vs 4.6 (p0.46) In-hospital bleed only
Ruiz-Nodar (2008) Retrospective cohort AF undergoing PCI TT (n213) vs DAPT (n174) 14.9 vs 9.0 (p0.19) 2 yr follow-up
Sarafoff (2009) Prospective cohort AF undergoing PCI TT (n306) vs DAPT (n209) 3.1 vs. 1.4 (p0.34) 2 yr follow-up
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Risk of Major bleed with TT

Study Design Patients Tx Major Bleeding Comments
Mattichak (2005) Retrospective cohort LV thrombus, AF for PCI TT (n40) vs DAPT (n42) 15 vs 0 GI Bleed (pNS) 21 vs 3.5 transfusion (p0.028) 12 mon follow-up
Konstantino (2006) Retrospective cohort TT (n76) vs DAPT (n2661) 2.6 vs. 0.6 (p0.03) AC indication unknown
Anand (2007) WAVE Study Prospective, randomized PAD TT (n1080) vs DAPT (n1081) 4 vs. 1.2 (plt0.001) RR 3.41 Life-threatening bleed Follow-up 2.5-3.5 yr
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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 ?

31

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

32
Recommendations

• Recommend D/C warfarin
• Discharge patient on
• 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 When Who
INR Daily until therapeutic Laboratory
Bleeding/Bruising Daily Pt
Warfarin D/C Three months Dr
Compliance Prescription refills Pharmacist
35
References

• 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
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  Guidelines for the Management of Patients With
  ST-Elevation Myocardial Infarction. Circulation.
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• 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. 19878975-80.
• Porter A, Kandalker H, Iakobishvili Z, Sagie A et
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• Brouwer MA, van den Bergh PJ, Aengevaeren WR, et
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