Oral Anticoagulants & Reversal Strategies ... Antidote Vitamin K, 4PCC None None None None Cost $0.36

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  • 4/9/2015

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    ISHP Spring Conference

    Boise 2015

    Oral Anticoagulants & Reversal Strategies

    Rob Wills, Pharm.D., BCPS Sr Clinical Manager of Pharmacy St. Luke’s Treasure Valley

    April 12th, 2015

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    1. Discuss current updates related to the new oral anticoagulants

    2. Describe the indications and differences between agents

    3. Evaluate the differences between reversal agents

    4. Identify the complications associated with the use of the new oral anticoagulants

    Objectives

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    J Am Coll Cardiol. 2012;59(16):1413-1425. doi:10.1016/j.jacc.2012.02.008

    4

    Wisconsin Sweet Clover & Rodenticide

    ISCONSIN

    LUMNI

    ESEARCH

    OUNDATION

    Wardrop & Keeling. British Journal of Haematology, 2008:141;757-763

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    5

    What’s Wrong With WARFARIN?

    Chest. 2008;133(6_suppl):160S-198S

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    Well Established Guidelines

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    What’s Wrong With WARFARIN?

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    � Slow on/off

    Reversibility with Phytonadione

    � Food Interactions

    http://theanswerpage.com/uploaded/images/warfarin/warfarin_2-1.png http://www.clinicalcorrelations.org/wp-content/uploads/2011/07/health-benefits-of-vitamin-k.jpg

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    Year in the life of a Warfarin patient

    10

    0

    1

    2

    3

    4

    5

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    IN R

    R e a d

    in g

    INR Trend 2013

    Antibiotic

    Year in the life of a Warfarin patient

    Trip to Europe

    Stomach bug

    New diet Thanksgiving

    January March September December

    INR

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    11

    ACC/AHA/ESC guidelines: Fuster V et al. Circulation 2006;114:e257–354 and Eur Heart J 2006:27:1979–2030.

    Time in Therapeutic Range (TTR)

    44 47 48 49 49

    53 53 54 55 55 56 56 56 57 58 58

    60 60 62 62 64 64 64 64 64 65 65 66 66 66

    67 68 68 70 70 70 71 71 72 72 72

    74 74 77

    0

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    40

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    Wallentin L, et al. Lancet. 2010 Sep 18;376(9745):975-83. PMID: 20801496.

    USA

    Preventing Afib Related Strokes. Boston University Anticoagulation Forum. Accessed 12-28-2014

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    13

    What’s Wrong With WARFARIN?

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    a) Rapid onset-offset

    b) Predictable pharmacokinetics/pharmacodynamics

    c) Low risk of bleeding

    d) Low risk of drug-drug or drug-food interactions

    e) All of the above

    Question: What are the ideal characteristics of an oral anticoagulant?

    National warfarin and dabigatran treatment visits, 2007 to 2011.

    Kirley K et al. Circ Cardiovasc Qual Outcomes. 2012;5:615- 621

    Copyright © American Heart Association, Inc. All rights reserved.

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    Quarterly prescription expenditures for warfarin and dabigatran (retail value), 2007 to 2011.

    Kirley K et al. Circ Cardiovasc Qual Outcomes. 2012;5:615- 621

    Copyright © American Heart Association, Inc. All rights reserved.

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    � Approved 2010

    � Use ���� 4-fold

    � FDA - reports of serious and fatal bleeds

    Dabigatran (Pradaxa®)

    Pradaxablood.com

    McConeghy KW, et al. Pharmacotherapy. 2014;34(6):561-569 Southworth et al. N Engl J Med 2013; 368:1272-1274

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    Dabigatran (Pradaxa®)

    McConeghy KW, et al. Pharmacotherapy. 2014;34(6):561-569 Southworth et al. N Engl J Med 2013; 368:1272-1274

    Warfarin Dabigatran (Pradaxa®)

    Adverse Reports

    2038 9029

    Bleeding Events

    637 (32%) 2347 (26%)

    Fatal outcomes

    46 (7.1%) 348 (15%)

    Lower bound est 150 bleeding fatalities per 100,000 dabigatran patient years

    20

    NOAC – FDA Approval Status

    Indication Dabigatran Pradaxa®

    Rivaroxaban Xarelto®

    Apixaban Eliquis®

    Edoxaban Savaysa®

    Atrial fibrillation

    FDA approved FDA approved FDA approved FDA approved

    VTE Treatment FDA approved FDA approved FDA approved FDA approved

    VTE Prevention, Ortho surgery

    No FDA activity

    FDA approved FDA approved No FDA activity

    Adapted from Desai – Novel Oral Anticoagulants. ISHP Fall Conference 2014

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    Atrial Fibrillation - Stroke

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    Stroke Epidemiology - CDC

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    � Age 84

    � 3+ yr hx of afib

    � HTN

    � CHADS2 ≥ 2

    � Currently on wafarin – INR TTR ~ 50%

    � Minor complaints of bruising and nose bleeds

    � SCr 1.6, Wt 81 kg

    Mary

    http://www.atrialfibrillation.com.au/images/Practice/ivy.jpg

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    http://theanswerpage.com/uploaded/images/afib3/afib3_5-1.png

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    Risk Category Recommendation

    CHA2DS2-VASc = 0 No Therapy

    CHA2DS2-VASc = 1 OAC or ASA or no therapy

    CHA2DS2-VASc ≥ 2 OAC

    Unstable INR Dabigatran, Rivaroxaban or Apixaban

    2014 AHA/ACC/HRS Atrial Fibrillation Guidelines

    January CT et al. J Am Coll Cardiol. 2014 Mar 28

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    http://afibprofessional.cardiosource.org/~/media/Images/Science%20and%20Quality/Hot%20Topics/hottopic_09272011 _hasbled.ashx

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    http://neurosurgerysurvivalguide.com/roundy/HAS- BLED%20Bleeding%20risk.png

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    HAS-BLED vs. CHADS-VASc

    http://img.medscape.com/article/759/348/759348-tab2.jpg

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    Drug Feature

    Warfarin Dabigatran Pradaxa®

    Rivaroxaban Xarelto®

    Apixaban Eliquis®

    Edoxaban Savaysa®

    Target Vitamin K Thrombin Factor Xa Factor Xa Factor Xa

    Dose Freq Daily Twice Daily Daily Twice daily Once Daily

    Onset Slow Rapid Rapid Rapid Rapid

    Peak effect 4 to 5 days 1 to 2 hours 2 to 3 hours 1 to 2 hours 1 to 2 hours

    Offset Long Short Short Short Short

    Half-life 40 hours 12 to 17 hrs 7 to 11 hours 12 hours 10 to 14 hrs

    Renal clearance

    None 80% 33% active (70% total)

    25% 50%

    Interactions Many P-gp CYP3A4;P-gp CYP3A4;P-gp P-gp

    Monitoring Yes No No No No

    Dialyzable No Yes No No No

    Antidote Vitamin K, 4PCC

    None None None None

    Cost $0.36 tab $3.16 day $4 per tab $6.80 day ?

    Adapted from Desai – Novel Oral Anticoagulants. ISHP Fall Conference 2014

    Drug Feature

    Warfarin Dabigatran Pradaxa®

    Rivaroxaban Xarelto®

    Apixaban Eliquis®

    Edoxaban Savaysa®

    Target Vitamin K Thrombin Xa Xa Xa

    Dose Freq

    Daily or Twice Daily?

    Daily

    Onset Slow Rapid Rapid Rapid Rapid

    Peak effect 4 to 5 days 1 to 2 hours 2 to 3 hours 1 to 2 hours 1 to 2 hours

    Offset Long Short Short Short Short

    Half-life 40 hours 12 to 17 hrs 7 to 11 hours 12 hours 10 to 14 hrs

    Renal clearance

    None 80% 33% active (70% total)

    25% 50%

    Interactions Many P-gp CYP3A4;P-gp CYP3A4;P-gp P-gp

    Monitoring Yes No No No No

    Dialyzable No Yes No No No

    Antidote Vitamin K, 4PCC

    None None None None

    Cost $0.36 tab $3.16 day $4 per tab $6.80 day ?

    Adapted from Desai – Novel Oral Anticoagulants. ISHP Fall Conference 2014

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    Drug Feature

    Warfarin Dabigatran Pradaxa®

    Rivaroxaban Xarelto®

    Apixaban Eliquis®

    Edoxaban Savaysa®

    Target Vitamin K Thrombin Xa Xa Xa

    Dose Freq

    Daily or Twice Daily?

    Daily

    Onset Slow Rapid Rapid Rapid Rapid

    Peak effect 4 to 5 days 1 to 2 hours 2 to 3 hours 1 to 2 hours 1 to 2 hour