OMFS Guidelines New Oral Anticoagulants

1. OMFS Guidelines New Oral Anticoagulants Sue Sanders Elective Care Divisional Quality Board May 2013

2. The New Oral Anticoagulants. • Generic Dabigatran RivaroxabanApixaban • Trade PradaxaXareltoEliquis

3. Mode of Action • Dabigatran (Pradaxa) is a thrombin inhibitor • Rivaroxaban (Xarelto) and Apixaban (Eliquis) are inhibitors of activated Factor Xa • Warfarin is a Vitamin K antagonist. Factors II, VII, IX, X

4. NOACs Background • 2008 • Registered for the Primary prevention of VTE in adults undergoing total hip and knee replacements.

5. NOACs Background • 2011 • Approved for the prevention of stroke and systemic embolism in adults with non valvular atrial fibrillation with one or more risk factors:- • previous stroke, TIA or systemic embolism • left ventricular ejection fraction <40% • Symptomatic heart failure • Age >75 • Age<65 with diabetes mellitus, coronary artery disease or hypertension.

6. NOACs • They are fast acting (Tmax Dabigatran 30mins) THEY DO NOT REQUIRE MONITORING!

7. NOACs Half Life PradaxaXareltoEliquis 150mg BD 15 – 20mg OD 5mg BD ~ 13hours 5 – 9 hours 12 hours Dependent on 11-13 hours in Renal clearance the elderly Warfarin ½ life – 40 hours.

8. Dabigatran (Pradaxa) ½ life • 80% renal excretion • ½ life can be significantly prolonged in patients with renal disease.

9. NOACs and coagulation parameters DabigitranRivaroxaban and Eliquis TEST PT Prolonged slightly Prolonged to 15-33secs at peak therapeutic levels APTT Prolonged but in a non Prolonged up to x2 baseline linear fashion. TT Markedly prolonged (x10) May be un-measureable INRNOT SUFFICIENTLY SENSITIVE AND CANNOT BE USED

10. NOACs Reversal • Evidence on reversal is patchy • If severe bleeding occurs within 24 hours of a dose of :- • Dabigatran – give FEIBA (Factor Eight Inhibitor Bypassing Activity and is an activated prothrombin complex concentrate) 50IU/kg IV(In the transfusion lab) • Rivaroxaban and Eliquis– give Octaplex (nonactivatedprothrombin complex concentrate) 50IU/kg/IV (In the transfusion lab)

11. NOACs – so what’s the problem? • A quantitative assessment of coagulation is not possible. • A qualitative assessment of coagulation is unreliable. (e.g. Pradaxa – “an aPTT>2x upper limit of normal at trough is associated with a higher risk of bleeding”.)

12. NOACs – So what’s the problem Part II? • The plasma concentration of the drug (and therefore the anticoagulation) will vary DAILY. • There may be one peak and trough (Rivaroxaban OD) or two (Dabigatran and Eliquis BD) Warfarin – once stabilised the plasma concentration remains within 1 INR unit. e.g. 2 - 3

13. NOAC Plasma concentrationDabigatran clearance of a 200mg dose

14. NOACs – So what’s the problem Part III? • No definitive guidance on the management of these patients in relation to dental treatment. • The patient information leaflets of all 3 drugs give no specific advice. • In relation to surgery, advice varies from “do exactly as your Dr says” and “ you may need to stop”. • SPC in relation to surgery advises stopping at least 24 hours pre-op (Rivaroxaban and Eliquis). • Following the renal clearance chart (Dabigatran)

15. NOACs – So what’s the problem Part IV? Dear Dentist, “Similar to warfarin, there may be some procedures which, at the discretion of the dentist, can be carried out with no discontinuation of therapy.” BoehringerIngelheim Pradaxa 6th August 2012

16. NOACs Management of Dental Treatment “Practical Guide Dabigatran Guidance for use in Particular Situations.” Heidbuchel et al Belgium Sept 2011

17. NOACs Heidbuchel et al 2011Recommendations • Dabigatran should not necessarily be discontinued for the extraction of 1-3 teeth, paradontal surgery, abscess incision or implants. • Procedure should be 12 hours after the last dose (8am -> surgery 8pm) • Least possible trauma • Wound should be sutured • Patient can only leave when bleeding completely stopped. • Tranexamic Acid M/W 5% QDS 5/7 (clot stabilisation only) • Oral and written instructions • Patient to contact dentist in case of bleeding that does not stop spontaneously. • Dentist to be available after hours

18. NOACs Heidbuchel et al 2011Recommendations • If the decision is to discontinue Dabigatran should be stopped 24h prior to extraction and resumed once haemostasis is achieved. • For more extensive intervention the patient should be referred to a maxillofacial surgeon!

19. NOACs – So what’s the Problem Part V? • There has been an exponential rise in prescribing • 15 patients Dec 2012 • Over 150 patients May 2013 • 400 patients are eligible • Rivaroxaban will be the drug of choice. • No new patients will be Rx Dabigatran Michelle Grundy Anticoagulation Service Waters Meeting HC

20. NOACs The Future? Warfarin 3p each Rivaroxaban £1.71 each Apixaban £2.10 each Dabigatran £ 1.26 each Monitoring No Monitoring

21. NOACs – the solution? Awareness and vigilance. Guidelines for management of NOAC patients - minor procedures - major procedures elective (+/- bridging) - emergency haemorrhage protocol Audit

22. NOACs Draft Guidelines • Safe. • Universal. • Suitable for both Primary, Tier 2 and Secondary care. • Clear for the clinician. • Clear and easy for the patient to follow.

23. NOACs Draft Guidelines (Proposed ) • Omit NOAC on the morning of surgery. • Usual local measures / judicious extractions etc. • Recommence NOAC the following day. For simple elective procedures such as extractions, apicetomies, biopsies, soft tissue surgery, and some fractures excluding orbital floor injuries.

24. NOAC Guidelines For emergency surgery, or more major procedures including Head and Neck, orbital floor surgery, Parotid / submandibular gland surgery, soft tissue surgery in the neck etc – haematology advice should be sort on a case by case basis, particularly in respect of recommencing NOACs in situations where post op bleeding could be problematic.

25. NOACs Draft Guidelines • Low Clot Risk patients. PE/DVT >6 anticoagulated >6 weeks Atrial fibrillation Peripheral vascular disease. • High clot risk patients. • PE/DVT within last 6 weeks (surgery should be deferred if possible) • Recurrent PE/DVT • Prosthetic heart valves • Antiphospholipid syndrome • Patients with active cancer • AF patients with a previous stroke or TIA

26. NOAC Draft Guidelines • Complies with the Trust Draft Guidelines for Anticoagulation of Adult Patients (consultation) • “Dabigatran, rivaroxaban, apixaban and other newer oral anticoagulants (NOACs) have quick onset of action so do not require a switch over to heparin for high clot risk patients as required with Warfarin. This also means that high and low clot risk patients are dealt with in the same way – i.e. for elective procedures simply stop the drug and allow 24 hours to elapse before surgery commences. In patients with renal failure longer may be required (Dabigatran). NOACs can be recommenced 24 hours post op.”

27. NOAC Draft Guidelines • OMFS proposed guidelines have been approved by: • Dr Mark Grey Consultant Haematologist • Dr AmbarBasu Chair, Hospital Thrombosis Committee

28. NOAC Audit Proposal • Prospective audit of all NOAC patients presenting for surgery – extractions, biopsies, I & D, trauma, H & N, across the Unit. • Audit any post extraction haemorrhage patients presenting via A & E and the treatment room at Blackburn.

29. Thank you