1. DR DIPTI CHITNAVIS HAEMATOLOGY CONSULTANT WEST SUFFOLK HOSPITAL JANUARY 2014 Update on the new oral anticoagulants; 12 months on

2. Overview Indications for oral direct inhibitor anticoagulants Key facts to remember Practical issues -CAREFUL PATIENT SELECTION -CONTRAINDICATION -CAUTIONS -DOSE REDUCTIONS -DRUG INTERACTIONS -CLOTTING TESTS -COUNSELLING Annual review/clinical surveillance Case studies Summary Future directions Primary care prescribing data

3. Indications for ODIs Stroke prevention in non-valvular AF (dabigatran, rivaroxaban, apixaban) Prophylaxis of VTE in adults undergoing hip/knee replacement (dabigatran, rivaroxaban, apixaban) Treatment of DVT and prophylaxis of recurrent DVT/PE in adults- NICE TA 261 (rivaroxaban) Treatment of PE and prevention of recurrent VTE in adults- NICE TA 287 (rivaroxaban)

4. Key facts to remember No head to head ODI trials Poorly represented patient groups in trials: >80 yrs 100kg INR 3-4* Antiphospholipid syndrome* High bleeding risk* *(VTE trials) No antidote Urgent, reliable reversal not established Long term effects unknown Safeguards applicable to warfarin should be applied to ODIs

5. Practical issues Careful patient selection- NPSA TTR>60% Contraindications- pregnancy, <18yrs, ketoconazole, Lactose intolerance (rivaroxaban), Cr. Cl. <30ml/min (dabigatran), Cr. Cl. <15ml/min (rivaroxaban, apixaban) Caution in renal impairment Caution in hepatic impairment

6. Practical issues Dose reductions  Dabigatran- >80yrs, (75-80yrs), <50kg, Cr. Cl.<50ml/min, gastrointestinal Sx/other bleeding risk  Rivaroxaban- Cr. Cl. 15-49ml/min, high bleeding risk  Apixaban- Cr. Cl. 15-29ml/min, high bleeding risk, at least 2 of: >80yrs/ 133 Dose insufficiency?  NEJM June 2013 case report ischaemic stroke in patient 153kg Drug interactions- take dabigatran 2hrs before a PPI Amiodarone, clarithromycin, quinidine

7. Practical issues Clotting tests  Baseline: FBC, U&E, Cr.Cl, LFT, APTT, PT, (TT)  Not INR  D-dimers lowered by ODIs- do not use for assessment for VTE

8. Practical issues Counselling Document  Indication, drug, dose, duration, review date  Copy in notes and to patient (signed and dated)  Lack of antidote  How to take Dabigatran- whole, with/without food, 2 hrs pre PPI, open blister pack just before use. Rivaroxaban- with food

9. Practical issues Counselling Compliance- Short half- life  Dabigatran 12-14 hrs (Cr. Cl. >80mls/min) 27hrs (Cr. Cl. <30mls/min)  Rivaroxaban 5-9hrs (young) 11-13hrs (elderly)  Apixaban approx. 12hrs  Warfarin 40hrs

10. Practical issues Counselling- missed dose Dabigatran  Take missed dose up to 6hrs prior to next scheduled dose; if <6hrs to go, omit missed dose and continue with usual schedule. Do not double dose to catch up. Rivaroxaban  Take missed dose immediately on the day due, even if dosing is b.d. (DVT/PE). If dosing is o.d., do not double dose to catch up. Apixaban  Take missed dose immediately, then continue with b.d. intake.

11. Practical issues Counselling Overdose  Document drug, dose, time taken, Creatinine Clearance Bleeding/injury  Who to contact if minor/major bleeding/head injury

12. Practical issues Counselling Patient information sheet Patient alert card Patient follow-up card for A.F.  European Heart Assoc.(WSH part 1 ODI guideline appendix 6) Set up formal registry for review

13. Practical issues Annual review/clinical surveillance Guided by Creatinine Clearance  6weekly to annually Medication change  Antiplatelets, NSAIDs, interactions, nephrotoxics) Discharge form secondary care  May be on extended prophylaxis Bleeding Consider checking coagulation status (in addition to baseline) at:  extremes of weight, compliance issues, overdose, bleeding, pre invasive procedures, deteriorating renal/hepatic function. Report adverse events

14. Summary 1 New ODI for Stroke prevention in AF (apixaban) New indications for ODIs (rivaroxaban for VTE) Trials not representative of all patient groups Calculate and monitor Creatinine Clearance Clotting tests- D-dimers not for VTE assessment

15. Summary 2 Practical considerations  Dose alterations/drug interactions  Counselling- copy to patient, drug alert cards, information leaflets, how to take, compliance, missed dose, contacts if bleed/injury  Formal registry for regular review- AF follow-up card  Report adverse events

16. Future directions Apixaban & dabigatran for VTE Studies on gastro-intestinal bleeds & coronary events Studies on clotting tests Studies on management of bleeding Phase IV long-term post marketing surveillance ROSE study

17. Primary Care Prescribing Data Linda Lord Head of Medicines Management 17

21. QUESTIONS? Thank you