1. Approach to the newer
anticoagulants
Dr Melita Kenealy
Consultant Haematologist
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. 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.
5. PRADAXA (DABIGATRAN) XARELTO (RIVAROXABAN)
ACTION Direct thrombin inhibitor Factor Xa inhibitor
PK 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 interactions
INDICATION Approved VTE proph (PBS) and Approved VTE proph (PBS), AF and
nonvalv AF+RF treatment DVT/PE
DOSE 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/d
MONITORING 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 antiXa
PERIOP Mx CrCL>50 stop 2+ days *Withdraw 12-24hrs
CrCl 30-50 stop 3-5d
9. 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
