Oral anticoagulants in the 21 st century: A practical guide to using newer Agents

1. Oral anticoagulants in the 21st century: A practical guide to using newer Agents Katherine Vogel Anderson, Pharm.D., BCACP University of Florida Colleges of Pharmacy and Medicine

2. Disclosures I have nothing to disclose

3. Case • BV is a 75 year old white male who has just been diagnosed with a. fib. His past medical history is significant for hypertension (taking chlorthalidone) and seasonal allergies. • Which oral anticoagulant do you recommend? • A. Apixaban • B. Dabigatran • C. Rivaroxaban • D. Warfarin

4. Objectives • Identify new oral anticoagulants (OACs) • Determine the current place in therapy for OACs • Review appropriate transitions between parenteral anticoagulants and OACs (and vice versa) • Highlight pharmacotherapy scenarios when changing between OACs • Identify OAC options peri-procedure

5. A History Lesson…

6. *All are FDA approved for stroke prevention secondary to a. fib

7. dabigatran warfarin rivaroxaban and apixaban

8. FDA-Approved Doses Also approved for VTE treatment and prevention

9. If it isn’t broken, why fix it? • What’s wrong with warfarin? • Monthly monitoring • Drug interactions • Takes lots of time…

10. In a nutshell… Katsnelson M et al. Circulation 2012;125: 1577-1583

11. A wise man once said… “Inferiors revolt in order that they may be equal, and equals that they may be superior. Such is the state of mind, which creates revolutions.” —Aristotle. In: Politics. Book V; Part II; 350 B.C.E. anticoagulation Nedeltchev K. Stroke 2012;43: 922-923

12. Back to our case… • Which oral anticoagulant do you recommend? • A. Apixaban • B. Dabigatran • C. Rivaroxaban • D. Warfarin

13. Warfarin • Pharmacogenomic dosing? • Regardless – treat to an INR between 2 and 3 You JJ et al. Chest 2012;141(2)(Suppl): e531S-e575S Coumadin (warfarin) package insert. Princeton, NJ: Bristol-Myers Squibb Company; 2011 Oct.

14. But… • Which oral anticoagulant do you recommend? • A. Apixaban • B. Dabigatran • C. Rivaroxaban • D. Warfarin

15. Pros  the oldest of the new Cons  GI intolerance; renal dose not prospectively studied Heidbuchel H et al. Europace 2013;15: 625-651

16. But… • Which oral anticoagulant do you recommend? • A. Apixaban • B. Dabigatran • C. Rivaroxaban • D. Warfarin

17. Pros  once daily dosing; renal adjustments Cons  once daily dosing; food requirement Heidbuchel H et al. Europace 2013;15: 625-651

18. But… • Which oral anticoagulant do you recommend? • A. Apixaban • B. Dabigatran • C. Rivaroxaban • D. Warfarin

19. Pros  renal dose prospectively studied Cons  twice daily dosing; newest of the new Heidbuchel H et al. Europace 2013;15: 625-651

20. Some considerations • Although new OACs are substrates for P-gp and CYP, they are not inhibitors • PPI use does not have a clinical effect on efficacy • Bleeding risk increases with antiplatelet agents • Compliance is key  effectiveness fades fast • 12 – 24 hours after last dose = no anticoagulation

21. The decision is made... • … A new OAC will be prescribed for BV So – what’s next? Do we really NOT monitor? What if BV has a procedure? What if BV wants to switch to warfarin?

22. Let’s get started… Heidbuchel H et al. Europace 2013;15: 625-651

23. Patient anticoagulation cards: www.noacforaf.eu • PPI: No prospective evidence, but consider a PPI for high risk patients (i.e. history of GI bleed) • Follow up visits: • Compliance • S/Sx thromboembolism and/or bleeding • Side effects • Medication reconciliation • Labs: 3, 6, 12 months and as needed Heidbuchel H et al. Europace 2013;15: 625-651

25. Coagulation Monitoring Heidbuchel H et al. Europace 2013;15: 625-651

26. Transitions in Therapy • To a new OAC… • From heparin  upon discontinuation (~2 hours) • From low molecular weight heparin (LMWH)  when the next dose of LMWH is due • From a new OAC… • To warfarin similar to “bridging” • The new OAC is taken simultaneously with warfarin until the INR is within the appropriate therapeutic range • To LMWH  when the next dose of OAC is due Heidbuchel H et al. Europace 2013;15: 625-651

27. Transitions in Therapy • From warfarin to a new OAC: • As soon as the INR is less than 2 • If INR is between 2 and 2.5  start the next day • For INR greater than 2.5  It depends  • How high is the INR? • Wait and hold • Draw a new INR • If INR is less than 2.5, proceed as above Heidbuchel H et al. Europace 2013;15: 625-651

28. Peri-procedural management of OAC When do you stop the new OAC? Evaluate • Patient factors = age, renal function, history of bleeding AND • Procedure factors • No bleeding risk • Minor bleeding risk • Major bleeding risk No need to hold the OAC Heidbuchel H et al. Europace 2013;15: 625-651

29. Peri-procedural management of OAC Hold the OAC 24 hours prior Hold the OAC 48 hours prior Resume OAC 6 – 8 hours after the procedure IF immediate and complete hemostasis is achieved AND re-bleeding risk is minimal. If invasive procedure, resumption of OAC may be deferred for 48 - 72 hours Heidbuchel H et al. Europace 2013;15: 625-651

30. Management of bleeding Heidbuchel H et al. Europace 2013;15: 625-651

31. Two Clinical Questions • What about aspirin? • Post-ACS: • ASA or clopidogrel + new OAC = increased bleeding • apixaban or rivaroxaban may be preferred • Within the first year  ASA + decreased OAC dose • After the first year  OAC alone • What about valves? • NOT for valvularatrial fibrillation • NOT for mechanical valve replacement Heidbuchel H et al. Europace 2013;15: 625-651

32. Back to our case… • Which oral anticoagulant do you recommend? • A. Apixaban • B. Dabigatran • C. Rivaroxaban • D. Warfarin

33. My answer • I’m old school… • But, if pressed to choose a new one….

34. Thanks for your attention!