Approach to new anticoagulants

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Information on new anticoagulant drugs

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Approach to new anticoagulants

  1. 1. Approach to the newer anticoagulants Dr Melita Kenealy Consultant Haematologist
  2. 2. Pradaxa (dabigatran) STROKE OR SYSTEMIC EMBOLISM (SSE)• RE-LY trial Non-inferiority Superiority P value P value – >18,000 pts non valv Margin=1.46 Dabigatran 110 mg BID <0.001 0.30 vs. warfarin AF + RF cf warfarin Dabigatran 150 mg BID <0.001 <0.001 – Rate of stroke or sys vs. warfarin 0.50 0.75 1.00 1.25 1.50 Hazard ratio embolism (%/yr) Error bars = 95% CI; BID = twice daily. Dabigatran etexilate is not approved for clinical use in stroke prevention in atrial fibrillation outside the US and Canada. Connolly SJ, et al. N Engl J Med 2010;363:1875-1876. • 1.54 (110mg), – similar major bleeding 1.11(150mg), 1.71(warfarin) • less ICH, less life threatening, more major GI bleed PFP stopped early due to bleeding concerns Criticisms – lack of stakeholder involvement
  3. 3. Xarelto (rivaroxaban)• ROCKET-AF (stroke and systemic embolism) – N=14,264 v warfarin – Noninf efficacy HR 0.79 (0.66-0.96) – Bleeding similar• EINSTEIN-DVT (acute sympto DVT) – N=3449 v clexane/warfarin 3-12mths – Noninferior efficacy HR 0.68 (0.44-1.04) – Similar major/sympt non-major bleeding rates 8% PFP about to be rolled out Have they learnt from others’mistakes??
  4. 4. PRADAXA (DABIGATRAN) XARELTO (RIVAROXABAN)ACTION Direct thrombin inhibitor Factor Xa inhibitorPK Peak 0.5-2h Peak 2-4h T1/2 12-17h Reduced bioavail fasting 85% renal excr T1/2 11-13h P-gp interactions Highly protein bound, predom renal 35% protein bound excretion, some metab CYP3A4, P-gp interactionsINDICATION Approved VTE proph (PBS) and Approved VTE proph (PBS), AF and nonvalv AF+RF treatment DVT/PEDOSE AF 150bd oral but reduce dose to AF 20mg/d (15mg CrCl30-50) 110bd if any other RF (age>75, DVT 15mgbd 3w then 20mg/d antiplt/NSAID CrCl 30-50) If CrCl 15-29ml/min 10mg/d CI if CrCl<30 VTE proph 10mg/d VTE proph 150-200mg/dMONITORING Not required BUT difficult. Not required but difficult APTT nonlinear, Rx x1.5-2.0 APTT, PT long but nonlinear TCT(sens,linear), Hemoclot Chromogenic antiXaPERIOP Mx CrCL>50 stop 2+ days *Withdraw 12-24hrs CrCl 30-50 stop 3-5d
  5. 5. Pradaxa peri-op
  6. 6. PRADAXA (DABIGATRAN) XARELTO (RIVAROXABAN)REVERSAL None proven None proven Stop drug Stop drug Charcoal <2h Charcoal<8h Dialysable Not dialysable PTX reversed coag tests in healthy volunteers Can try: Platelets Can try: Antifibrinolytics Platelets FFP Antifibrinolytics Prothrombinex FFP rFVIIa Prothrombinex rFVIIa
  7. 7. Management of bleeding
  8. 8. Summary• New agents useful in subgroup of patients• No simple test to establish anticoagulant effect• Management of bleeding – Resuscitate, treat source, stop drug, call haematologist! – No effective means of reversal, but short t1/2

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