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Kelly-DOAC_overview_2017_fo.pptx
- 1. Warfarin, Your Days are Numbered! Linda R. Kelly PharmD PhC CACP Pharmacy Anticoagulation Specialist Presbyterian Healthcare System
- 2. Objectives • Identify and classify the available oral anticoagulants • Evaluate patient characteristics that would suggest using one product over another • Design a plan for switching from one oral anticoagulant to another • Manage oral anticoagulants in the peri- procedural period
- 3. Terminology • VKA-Vitamin K Antagonist (warfarin) • DOAC-Direct Oral Anticoagulant • TSOAC-Target Specific Oral Anticoagulant • NOAC-Novel (or New or Non-vitamin K) Oral Anticoagulant
- 4. Resources
- 5. Available Direct Acting Oral Anticoagulants (DOACs) • Dabigatran • Rivaroxaban • Apixaban • Edoxaban
- 6. DOAC Mechanism of Action Inhibits Factor Xa Rivaroxaban Apixaban Edoxaban Direct Thrombin Inhibitor Dabigatran
- 7. Focus on Venous Thromboembolism and Non-valvular Atrial Fibrillation
- 8. Marge is a 72 year old female with non-valvular atrial fibrillation (NVAF). She has been taking warfarin for stroke prevention. Her history also includes hypertension. What is her CHA2DS2- VASc score? Meet Marge
- 10. Marge comes to see you about starting a new product, bringing you a souvenir from her latest excursion. What factors should be considered when planning to start or switch a patient to a DOAC? Marge
- 12. DOAC Indications and Dosing NVAF DVT PE Rivaroxaban Apixaban 20 mg once daily with evening meal 5mg twice daily Rivaroxaban Apixaban 15 mg twice daily x 21 days 10 mg twice daily x 7 days 20 mg once daily with evening meal 5 mg twice daily
- 13. DOAC Indications and Dosing NVAF DVT PE Dabigatran Edoxaban 150 mg twice daily 60 mg daily Dabigatran Edoxaban LMWH lead in x 5-10 days LMWH lead in x 5-10 days 150 mg twice daily 60 mg daily
- 14. DOAC Renal Dosing Rivaroxaban NVAF CrCl 15-50 mL/min 15 mg once daily CrCl < 15 mL/min Use warfarin DVT/PE CrCl < 30 mL/min Use warfarin 2.5 mg Apixaban twice daily** NVAF Must meet 2 of the following Age 80 years or older Actual body weight 60 kg or less Serum Creatinine 1.5 mg/dL or greater **No dose reduction in DVT/PE patients. However, patients with SCr > 2.5 or CrCl < 25 mL/min not studied
- 15. DOAC Renal Dosing Dabigatran NVAF CrCl 15-30 mL/min 75mg bid CrCl < 15 mL/min Use warfarin DVT/PE CrCl < 30 mL/min Use warfarin Edoxaban NVAF CrCl >95 mL/min DO NOT USE CrCl 15-50 mL/min 30mg daily CrCl < 15mL/min Use warfarin DVT/PE CrCl 15-50 mL/min 30mg daily CrCl < 15mL/min Use warfarin
- 16. DOAC Hepatic Dosing Child- Pugh Class Rivaroxaban Apixaban A No Adjustment No Adjustment B Use warfarin Use with caution- limited clinical experience C Use warfarin Use warfarin Child- Pugh Score calculator can be found at PresNet Anticoagulation Oral Anticoagulants Rivaroxaban (Xarelto) Child-Pugh Classification Score
- 17. DOAC Hepatic Dosing Child- Pugh Class Dabigatran Edoxaban A No Adjustment No Adjustment B No Adjustment Use Warfarin C Use warfarin Use warfarin Child- Pugh Score calculator can be found at PresNet Anticoagulation Oral Anticoagulants Rivaroxaban (Xarelto) Child-Pugh Classification Score
- 18. Drug Interactions • Dabigatran: ▫ Substrate for p-glycoprotein • Rivaroxaban: ▫ Substrate for p-glycoprotein ▫ 51% CYP 3A4 metabolism • Apixaban: ▫ Substrate for p-glycoprotein ▫ 25% CYP 3A4 metabolism • Edoxaban ▫ Substrate for p-glycoprotein ▫ Minimal CYP 3A4 metabolism
- 19. Drug Interactions Common Interacting Classes ▫ Anticonvulsants including barbiturates ▫ Antiretrovirals ▫ Antifungals ▫ Antiplatelet drugs and NSAIDS Your favorite drug interaction program is your best friend
- 20. Focus on Venous Thromboembolism and Non-valvular Atrial Fibrillation
- 21. Is a DOAC a Good Choice For Marge? What should we consider before prescribing a DOAC?
- 22. DOAC Selection • DVT of leg or PE with active cancer • Pregnant • DVT of leg or PE without active cancer
- 23. Anticoagulant Selection • Valvular atrial fibrillation • Valve replacement • Myocardial infarction requiring dual antiplatelet therapy • Breast feeding
- 24. Anticoagulant Selection Does patient have CrCl < 30, mechanical heart valve, moderate to severe hepatic impairment (Child- Pugh B or C), significant drug-drug interactions6? Will the patient have trouble paying for a DOAC? Yes Yes No No • Valvular atrial fibrillation • Valve replacement • Myocardial infarction requiring dual antiplatelet therapy • Pregnant or breast feeding • Non-valvular atrial fibrillation • Secondary VTE prevention • VTE prophylaxis following knee/hip replacement surgery
- 25. Anticoagulant Selection Does patient have CrCl < 30, mechanical heart valve, moderate to severe hepatic impairment (Child- Pugh B or C), significant drug-drug interactions6? Yes Patient Characteristics Favoring DOAC • Highly like to be adherent with DOAC therapy and follow up plan • Reliable to notify health care provider about changes to health and pertinent medical issues • Confirmed ability to obtain DOAC on a longitudinal basis from a financial, insurance coverage and retail availability standpoint • Unstable diet or malnutrition • Frequent illness or health status changes • Frequent medicine changes or need for medications that interact with warfarin but not with DOAC • Frequent medical procedures with bleeding risk No Patient/ Family Preference
- 26. Anticoagulant Selection Patient/ Family Preference Drug 2 • Newer, less familiar • No diet interaction and fewer interactions with other medications • Cannot easily monitor level of anticoagulation and reversal agent may not be readily available • Frequent monitoring and dose changes not required • Bridging NOT required around procedures • Lower risk of intracranial hemorrhage Drug 1 • Older, more established • Strong interaction with diet and other medications • Reversible and easily monitored • Frequent monitoring and dose changes often required • Bridging may be required around procedures • Higher risk of intracranial hemorrhage
- 27. Drug affordability • Warfarin $ • Rivaroxaban, Apixaban, Dabigatran, Edoxaban $$$$ • Commercial plans (not Medicare/ Medicaid) ▫ Patient copay • Medicare ▫ Consider coverage gap ▫ TrOOP vs. Drug spend • Use sample card and/or coupon Sample clinic Patient pay
- 28. Drug affordability- Medicare • Medicare coverage gap or “Donut Hole” • Must pay deductible (PHS plan deductible= $0) • Copay ~$45 per month • Gap starts at $3700 total cost or “drug spend” ▫ This is copay + balance insurance pays ▫ In 2017, when in the gap patient pays ~51% cost for generic, ~40% for brand. ▫ Out of gap at $4,950 paid in out of pocket expenses • True out of pocket cost= “TrOOP” ▫ Cost the patient sees, copay, coinsurance, spending during the coverage gap
- 29. Drug Affordability- Medicare • Example- Rivaroxaban alone ▫ Rivaroxaban total cost= $431.4 ▫ Rivaroxaban copay = $45 ▫ Will meet gap in 8.6 months ($3700) ▫ After gap, drugs cost = $172.56 per month ▫ TrOOP ($4950 to get out of gap) $360 (on copays) before gap with no deductible $690.24 (4 months in gap) ▫ Drug spend for catastrophic = $4950 After gap $21.57 (5%) (if patient is on other medications)
- 30. Drug Affordability- Medicare • Example – Warfarin alone ▫ Warfarin total cost $6 (5 mg per day x 30 days. ) ▫ Warfarin copay= $4 ▫ Will not meet gap with warfarin ▫ In the gap, warfarin cost approx $3 ▫ After gap will pay $1.60 per month
- 31. Patient Assistance • Utilize patient savings cards ▫ Sample Cards 1st month free! Regardless of insurance plan. ▫ Copy Card $0 copay for commercial insurance ▫ Samples may be available
- 32. Patient selections takeaway • LMWH preferred in patients with active cancer • DOAC preferred in patients with DVT/ PE • NVAF -2016 European and Canadian guidelines recommend DOAC over warfarin, 2014 AHA/ACC/HRS guidelines do not recommend one over the other • Must consider patient co-morbidities and ability to afford therapy
- 33. Is a DOAC a Good Choice For Marge?
- 34. Questions?
- 36. Enoxaparin TO/FROM DOAC Stop old medication and start new medication when the next dose is due Abo-Salem J Thromb Thrombolysis (2014)
- 37. DOAC TO DOAC Stop DOAC 1 and start DOAC 2 when the next dose is due Abo-Salem J Thromb Thrombolysis (2014)
- 38. DOAC to Warfarin/Warfarin to DOAC Abo-Salem J Thromb Thrombolysis (2014)
- 39. Warfarin to DOAC • Discontinue warfarin • Begin rivaroxaban when INR below 3.0 • Begin dabigatran or apixaban when INR below 2.0
- 40. DOAC to warfarin • Need overlap therapy until INR equal or above 2.0 1. DOAC • May interfere with INR reading • Must use DOAC trough for INR draw • Make clear to the patient that they MUST go in for an INR draw right before next DOAC dose is due. OR 2. LMWH • Transition like normal LMWH bridge per PMG policy. • Start LMWH when next DOAC dose due.
- 41. Anticoagulant Transitions • Warfarin to DOAC, DOAC to Warfarin ** INR < 3.0 for Rivaroxaban
- 42. How Does Marge Switch from Warfarin to Rivaroxaban?
- 44. Peri-procedural bridging • Avoid overlapping LMWH and DOACS 1. Can the procedure be delayed until patient is not on anticoagulation therapy? 2. Is the bleeding risk of procedure high enough to warrant DOAC interruption? 1. Consult bleed risk tables. 3. Can we delay procedure to increase time for elimination? 1. DOAC elimination based on renal function. 4. Resume DOAC after hemostasis is achieved 1. Low bleed risk: 24 hours 2. High bleed risk: 48-72 hours.
- 45. MAPPP Online and App www.mappp.ipro.org
- 46. Bleeding Risk
- 47. Drug Renal Function Low Bleeding Risk Surgery High Bleeding Risk Surgery Resumption of Therapy Low Bleeding Risk High Bleeding Risk Rivaroxaban T ½ = 8-9 hrs CrCl >50 mL/min Last dose: 2 days before procedure *Skip 2 doses Last dose: 3 days before procedure *Skip 3 doses Resume on day after procedure (24 h postop) Resume 2-3 days after procedure (48-72 h postop) T ½ = 9 hrs CrCl 30-50 mL/min Last dose: 2 days before procedure *Skip 2 doses Last dose: 3 days before procedure *Skip 3 doses T ½ = 9-10 hrs CrCl 15- 29.9 mL/min Last dose: 3 days before procedure *Skip 3 doses Last dose: 4 days before procedure *Skip 4 doses Peri-Operative Management
- 48. Drug Renal Function Low Bleeding Risk Surgery High Bleeding Risk Surgery Resumption of Therapy Low Bleeding Risk High Bleeding Risk Apixaban T ½ = 7-8 hrs CrCl >50 mL/min Last dose: 2 days before procedure *Skip 4 doses Last dose: 3 days before procedure *Skip 6 doses Resume on day after procedure (24h postop) Resume 2-3 days after procedure (48–72h postop) T ½ = 17- 18 hrs CrCl 30-50 mL/min Last dose: 3 days before procedure *Skip 6 doses Last dose: 4 days before procedure *Skip 8 doses Peri-Operative Management
- 49. Drug Renal Function Low Bleeding Risk Surgery High Bleeding Risk Surgery Resumption of Therapy Low Bleeding Risk High Bleeding Risk Dabigatran T ½ = 14-17 hrs CrCl >50 mL/min Last dose: 2 days before procedure *Skip 4 doses Last dose: 3 days before procedure *Skip 6 doses Resume on day after procedure (24h postop) Resume 2-3 days after procedure (48-72h postop) T ½ = 16-18 hrs CrCl 30- 50 mL/min Last dose: 3 days before procedure *Skip 6 doses Last dose: 4–5 days before procedure *Skip 8-10 doses Peri-Operative Management
- 50. Peri-Operative Management Drug Renal Function Low Bleeding Risk Surgery High Bleeding Risk Surgery Resumption of Therapy Low Bleeding Risk High Bleeding Risk Edoxaban T ½ = 6-11 hrs CrCl >50 mL/min Last dose: 2 days before procedure *Skip 2 doses Last dose: 3 days before procedure *Skip 3 doses Resume on day after procedure (24h postop) Resume 2-3 days after procedure (48-72h postop)
- 51. DOAC temporary interruption 1. Allow for 95% drug elimination prior to procedure (~5 drug half lives) 2. Resume DOAC 24-72 hours post procedure based on bleeding risk
- 52. Case Study: MR. JF • Creatinine Clearance is about 60ml/min
- 53. Case Study: Mr. JF
- 54. Bleeding Risk
- 55. Drug Renal Function Low Bleeding Risk Surgery High Bleeding Risk Surgery Resumption of Therapy Low Bleeding Risk High Bleeding Risk Dabigatran T ½ = 14-17 hrs CrCl >50 mL/min Last dose: 2 days before procedure *Skip 4 doses Last dose: 3 days before procedure *Skip 6 doses Resume on day after procedure (24h postop) Resume 2-3 days after procedure (48-72h postop) T ½ = 16-18 hrs CrCl 30- 50 mL/min Last dose: 3 days before procedure *Skip 6 doses Last dose: 4–5 days before procedure *Skip 8-10 doses Peri-Operative Management
- 56. Overview • DOACS used for DVT/PE and NVAF ▫ Double check dosing for drug/ indication • DOACS may not be the best option for everyone ▫ Consider your patient and their preferences • DOACS come with added cost, but help is available • We can transition between drug classes with monitoring • DOAC temporary interruption AKA “peri-procedural bridging” is possible. ▫ Be aware of procedure bleeding risk and patient risk factors. ▫ Do not overlap LMWH with DOACS
- 57. Questions?
- 58. References • www.xarelto.com • Antithrombotic Therapy For Vte Disease: Chest Guideline And Expert Panel ReportKearon C, Akl EA, Ornelas J, et al.Chest. 2016;149(2):315-352. doi:10.1016/j.chest.2015.11.026 • Abo-salem E, Becker R. Transitioning to and from the novel oral anticoagulants: a management strategy for clinicians. J Thromb Thrombolysis. 2014;37(3):372- 9. • Connolly SJ, Milling TJ, Eikelboom JW, et al. Andexanet Alfa for Acute Major Bleeding Associated with Factor Xa Inhibitors. N Engl J Med. 2016;375(12):1131-41. • Burnett AE, Mahan CE, Vazquez SR, Oertel LB, Garcia DA, Ansell J. Guidance for the practical management of the direct oral anticoagulants (DOACs) in VTE treatment. J Thromb Thrombolysis. 2016;41(1):206-32. • Rechenmacher SJ, Fang JC. Bridging Anticoagulation: Primum Non Nocere. J Am Coll Cardiol. 2015;66(12):1392-403. • www.drugsafety.ipro.org Management of Anticoagulation in the Peri-Procedural Period • Thrombosis Canada. New/ Novel oral anticoagulants (NOACS): Peri-Operative Management