Pharmacy Services Anticoagulation post STEMI: warfarin for wall motion abnormality in the era of triple antithrombotics Jenelle Rogers VCH-PHC Pharmacy

Pharmacy ServicesPharmacy Services

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

antithrombotics

Jenelle Rogers

VCH-PHC Pharmacy Resident

2009-2010


Outline

• Objectives

• Case

• Background

• Clinical Question

• Review of Literature

• Recommendations

• Follow-up

• Monitoring


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


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


History of Present Illness

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


Past Medical History

• Dyslipidemia

• Obesity (140kg)

• Family history CAD (sister had MI at 55)

• No medications PTA


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


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


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)


Diagnostics

• 100% occlusion LAD• 20% occlusion RCA• 20% occlusion LCX

• Bare metal stent to LAD


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.


STEMI: Background• Full occlusion of coronary artery• Signs and symptoms:

– 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


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


STEMI: Treatment

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


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)


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


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?


Search Strategy

• Databases: Pubmed, Embase

• Search terms: warfarin or vitamin k antagonist, myocardial infarction, akinesis

• Results:– None


Approach

• No evidence, but still have to answer clinical question

• Try to extrapolate efficacy and toxicity of warfarin for this indication from available data


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


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

myocardial infarction

Johannessen et al.

Euro Heart Journal. 1987;8:975-80


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


Johannessen et al.


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


Quoted in the ACC/AHA GuidelinesStudy Method Patient

PopulationPrimaryEndpoint

Result

WARIS II:ASA vs. ASA +warfarin

3630 pts,randomized, multicenter, open-label, 4year followup

<75 yearswith acuteSTEMI

Death, nonfatalreinfarction, orthromboemboliccerebral stroke

Primaryendpoint:24.55 vs.17.4% (p=0.0005)Major bleed:0.17% vs.0.68% (p=0.001)

APRICOT II:ASA vs. ASA +warfarin

308 pts,randomized, multicenter, open-label, 3month follow up

<75 yearswith acuteSTEMItreated with fibrinolysis

Reocclusion of the

infarct relatedartery atangiographicfollow-up

Primaryendpoint:28% vs.15% (p=0.02)Major bleed:NSS (1.5%in both groups)


Risk of Major Bleed


Risk of Major Bleed with TTStudy Design Patients and Tx Major Bleed Comments

Manzano-Fernandez (2008)

Retrospective cohort

AF for PCI

TT (n=51) vs non-TT (n=53)

21.6% vs 3.8% (p=0.006)

TT use, baseline anemia were predictors of late major bleed

Rogacka (2008)


AF & other indication for PCI

TT (n=71) vs DAPT (n=56)

5.6 vs 3.6% (p=1.0)

Follow-up 21mon

Khurram (2006)

Retrospective Cohort

AF, LV thrombus for PCI

TT (n=107) vs DAPT (n=107)

6.6% vs 0% (p=0.014)

Follow-up ~220d


Risk of Major Bleed with TTStudy Design Patients and Tx Major Bleed Comments

Nguyen

(2007)


ACS with PCI

TT (n=580) vs DAPT (n=220)

5.9% vs 4.6% (p=0.46)

In-hospital bleed only

Ruiz-Nodar

(2008)


AF undergoing PCI

TT (n=213) vs DAPT (n=174)

14.9% vs 9.0% (p=0.19)

2 yr follow-up

Sarafoff (2009)

Prospective cohort

AF undergoing PCI

TT (n=306) vs DAPT (n=209)

3.1% vs. 1.4% (p=0.34)

2 yr follow-up


Risk of Major bleed with TTStudy Design Patients & Tx Major

BleedingComments

Mattichak (2005)


LV thrombus, AF for PCI

TT (n=40) vs DAPT (n=42)

15% vs 0% GI Bleed (p=NS)

21% vs 3.5% transfusion (p=0.028)

12 mon follow-up

Konstantino (2006)


TT (n=76) vs DAPT (n=2661)

2.6% vs. 0.6% (p=0.03)

AC indication unknown

Anand (2007)

WAVE Study

Prospective, randomized

PAD

TT (n=1080) vs DAPT (n=1081)

4% vs. 1.2% (p<0.001); RR 3.41

Life-threatening bleed

Follow-up 2.5-3.5 yr


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 = ?


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


Recommendations

• Recommend D/C warfarin

• Discharge patient on:– Clopidogrel x 1 month– ASA– Metoprolol– Ramipril– Simvastatin– Nicotine patch


Follow up

• Physician declined recommendation and continued with warfarin x 3 months


Monitoring

Parameter When Who

INR Daily until therapeutic Laboratory

Bleeding/Bruising Daily Pt

Warfarin D/C Three months Dr

Compliance Prescription refills Pharmacist


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 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.

Documents

Pharmacy Services Anticoagulation post STEMI: warfarin for wall motion abnormality in the era of triple antithrombotics Jenelle Rogers VCH-PHC Pharmacy