Jenelle Rogers VCH-PHC Pharmacy Resident 2009-2010

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 22:55 • Presented in ER (Williams Lake) at 23:10 • 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 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

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 >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

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)

16. 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

17. 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. 1987;8:975-80

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

23. 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)

25. Quoted in the ACC/AHA Guidelines

26. Risk of Major Bleed

27. Risk of Major Bleed with TT

28. Risk of Major Bleed with TT

29. Risk of Major bleed with TT

30. 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

33. Follow up • Physician declined recommendation and continued with warfarin x 3 months

34. Monitoring

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 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.