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Double trouble – A tale of butterflies and broken hearts

This article discusses the identification and treatment options for patients with atrial fibrillation and recent acute coronary syndrome. It critically appraises the AUGUSTUS trial and provides a monitoring plan for these patients. The goals of therapy, treatment options, and recommendations are also explored.

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Double trouble – A tale of butterflies and broken hearts

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  1. Double trouble – A tale of butterflies and broken hearts Tracy Souza - LMPS Resident July 31th/19

  2. Learning Objectives • Identify patients with AFIB and recent ACS who may be suitable for DOAC + Clopidogrel • List treatment alternatives for patients with AFIB and recent medically managed NSTEMI • Critically appraise the AUGUSTUS trial and apply evidence to a patient case • Formulate a monitoring plan for patients with atrial fibrillation and recent NSTEMI

  3. Meet the Patient

  4. Meet the Patient

  5. ROS

  6. Labs

  7. Labs • 2019 Outpatient INRs: • Feb: 1.7 • Mar: 1.9 • April: 2.1 • May: 1.5 • June: 2

  8. Investigations • July 18th ECG: QTc = 445, Mild T Wave inversion, NSR CXR: Mild consolidation, pleural effusions Blood and urine Cx: negative • Dx: NSTEMI (medical management)

  9. DTPs • At risk of cardioembolic stroke secondary to subtherapeutic INR • Possibly at increased risk of bleed and cardioembolic stroke secondary to receiving warfarin as opposed to DOAC • At increased risk of mortality secondary to not receiving an ACEI or ARB post-MI

  10. DTPs • At increased risk of mortality and decline in EF secondary to hydralazine not at heart failure target dose • At risk of recurrent gout attack secondary to elevated serum urate with no preventative therapy • At risk of recurrent CV event secondary to uncontrolled hypertension

  11. DTPs • At increased risk of mortality secondary to aggressive A1C lowering of <7% • Ineffective drug therapy with acetaminophen for gout pain • Unnecessary drug therapy with regularly scheduled ranitidine despite no symptoms of GERD

  12. Goals of Therapy • Minimize risk of mortality • Minimize risk of cardioembolic stroke and systemic thrombosis • Optimization in management of concomitant disease states (HTN, NSTEMI, HFrEF) • Maximize quality of life and function • Minimize risk of ADRs • Minimize complex medication regimen • Decrease family burden

  13. CCS 2018 AFIB1

  14. Guidelines • AHA 20192 Atrial Fibrillation Focus Update • OAC + Clopidogrel • ESC 20163 Atrial Fibrillation Guidelines • OAC + Clopidogrel up to 12 months 🡪 OAC alone

  15. Treatment Options • DOAC + P2Y12 inhibitor • Warfarin + P2Y12 inhibitor • ASA + P2Y12 inhibitor + OAC

  16. Treatment Alternatives • DOAC + P2Y12 inhibitor • Warfarin + P2Y12 inhibitor • ASA + P2Y12 inhibitor + OAC

  17. PICO

  18. Search Strategy and Results • EMBASE, Medline, Cochrane, Pubmed • Terms: • Anticoagulant/tu OR anti-vitamin K OR Warfarin • AND atrial fibrillation • AND acute coronary syndrome • AND Hemorrhage OR bleed • MA, SR, RCT, human trials, English • Results: N = 8 • 1 relevant RCT

  19. AUGUSTUS4

  20. AUGUSTUS

  21. AUGUSTUS

  22. AUGUSTUS

  23. AUGUSTUS Apixaban Warfarin

  24. AUGUSTUS

  25. AUGUSTUS (Results)

  26. AUGUSTUS (Results) Apixaban Warfarin HR (95% CI) SS

  27. AUGUSTUS (Results)

  28. AUGUSTUS Author Conclusion: • Apixaban is superior to warfarin in terms of major and minor bleeds

  29. AUGUSTUS

  30. AUGUSTUS

  31. AUGUSTUS My Interpretation: • Apixaban has decreased risk of minor bleeds and may decrease risk of major bleed • Apixaban may be superior compared to warfarin in decreasing ischemic events

  32. Applicability to Patient • Higher stroke risk than most patients in trial (CHADS2VASc = 6 vs. 3.9 +/- 1.6) • Eligible • Renal function • Exclusion criteria N/A

  33. Recommendations • Discontinue warfarin • Start apixaban 5mg PO BID (INR<2)

  34. Rationale • PTA subtherapeutic INRs x 4 months, would meet criteria for Special Authority • Lower bleed risk in elderly CKD patient • Possibly lower stroke risk • Family burden of taking patient to blood tests • Can blister pack apixaban, warfarin challenging given frequent dose changes

  35. What happened next • Team continued with warfarin – concerns with renal function if it declines • Patient was discharged the next day on July 25th

  36. Monitoring Plan (Efficacy)

  37. Monitoring Plan (Safety)

  38. References • 6. Andrade J, Verma A, Mitchell L, Parkash R, Leblanc K, Atzema C et al. 2018 Focused Update of the Canadian Cardiovascular Society Guidelines for the Management of Atrial Fibrillation. Canadian Journal of Cardiology. 2018;34(11):1371-1392. • January C, Wann L, Calkins H, Chen L, Cigarroa J, Cleveland J et al. 2019 AHA/ACC/HRS Focused Update of the 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society in Collaboration With the Society of Thoracic Surgeons. Circulation. 2019;140(2). • Kirchhof P, Benussi S, Kotecha D, Ahlsson A, Atar D, Casadei B et al. 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Kardiologia Polska. 2016;:1359-1469. • Lopes R, Heizer G, Aronson R, Vora A, Massaro T, Mehran R et al. Antithrombotic Therapy after Acute Coronary Syndrome or PCI in Atrial Fibrillation. New England Journal of Medicine. 2019;380(16):1509-1524. • Stiles S. Apixaban for AF in ESRD: Fewer Strokes, Major Bleeds vs Warfarin [Internet]. Medscape. 2019 [cited 31 July 2019]. Available from: https://www.medscape.com/viewarticle/900050#vp_2 • Stamellou E, Floege J. Novel oral anticoagulants in patients with chronic kidney disease and atrial fibrillation. Nephrology Dialysis Transplantation. 2017;33(10):1683-1689. • HAS-BLED Tool – What is the Real Risk of Bleeding in Anticoagulation? - American College of Cardiology [Internet]. American College of Cardiology. 2019 [cited 31 July 2019]. Available from: https://www.acc.org/latest-in-cardiology/articles/2014/07/18/15/13/has-bled-tool-what-is-the-real-risk-of-bleeding-in-anticoagulation • Hamada S, Gulliford M. Mortality in Individuals Aged 80 and Older with Type 2 Diabetes Mellitus in Relation to Glycosylated Hemoglobin, Blood Pressure, and Total Cholesterol. Journal of the American Geriatrics Society. 2016;64(7):1425-1431.

  39. References • Ezekowitz J, O'Meara E, McDonald M, Abrams H, Chan M, Ducharme A et al. 2017 Comprehensive Update of the Canadian Cardiovascular Society Guidelines for the Management of Heart Failure. Canadian Journal of Cardiology. 2017;33(11):1342-1433. • Cohn J, Archibald D, Ziesche S, Franciosa J, Harston W, Tristani F et al. Effect of Vasodilator Therapy on Mortality in Chronic Congestive Heart Failure. New England Journal of Medicine. 1986;314(24):1547-1552. • Macle L, Cairns J, Leblanc K, Tsang T, Skanes A, Cox J et al. 2016 Focused Update of the Canadian Cardiovascular Society Guidelines for the Management of Atrial Fibrillation. Canadian Journal of Cardiology. 2016;32(10):1170-1185. • Dewilde W, Oirbans T, Verheugt F, Kelder J, De Smet B, Herrman J et al. Use of clopidogrel with or without aspirin in patients taking oral anticoagulant therapy and undergoing percutaneous coronary intervention: an open-label, randomised, controlled trial. The Lancet. 2013;381(9872):1107-1115. • Granger C, Alexander J, McMurray J, Lopes R, Hylek E, Hanna M et al. Apixaban versus Warfarin in Patients with Atrial Fibrillation. New England Journal of Medicine. 2011;365(11):981-992. • Medscape Log In [Internet]. Medscape.org. 2019 [cited 31 July 2019]. Available from: https://www.medscape.org/viewarticle/883986 • Medscape Log In [Internet]. Medscape.org. 2019 [cited 31 July 2019]. Available from: https://www.medscape.org/viewarticle/888516_transcript

  40. Questions?

  41. Supplementary Slides

  42. Apixaban in ESRD5

  43. Apixaban in ESRD2 • AHA 2019 Focus Update

  44. Dosing of DOACs in CKD2

  45. Site of Action of DOACS6

  46. AUGUSTUS (Results)

  47. A1C Targets in the Elderly8 • Diabetes Canada: • Functionally dependent: 7.1-8.0% • Dementia/Frail: 7.1-8.5% • Mortality in Individuals Aged 80 and Older with Type 2 Diabetes Mellitus in Relation to Glycosylated Hemoglobin, Blood Pressure, and Total Cholesterol. • Cohort study (UK), N = 25000 • 35% = Coronary heart disases • Lowest mortality: A1C 7-7.4%

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