This document summarizes key findings from major clinical trials comparing new oral anticoagulants (NOACs) like dabigatran, rivaroxaban, and apixaban to warfarin for stroke prevention in patients with atrial fibrillation. The trials found the NOACs to be as effective or more effective than warfarin in reducing strokes with lower rates of major bleeding, especially intracranial bleeding. Dabigatran was associated with more gastrointestinal bleeding compared to warfarin. Rivaroxaban and apixaban showed similar or lower rates of bleeding than warfarin. All NOACs were found to be non-inferior or superior to warfarin for

1. NOAC
Praneel Kumar

3. Fibrinogen Fibrin
Common Pathway
Thrombin
Xa
Prothrombin
Clot
Xa
Blocker
Apixaban
Rivaroxaban
Dabigatran
New Oral Agents

4. Dabigatran(Pradexa)
• Bioavalibility – 3-7% ( do not open,break,chew or crush capsule)
• Half life – 12 -17 hrs
• Elimination – 80% renal clearance
• Metabolism – minimal ( not a substrate,inhibitor or inducer of CYP
450 enzymes)
• Contraindicated in patient with Cr clearance <30ml/min and reduced
dose is recommened with Cr clearance of 30 -50

5. RE – LY Trial
• Biggest Dabigatran trial - 18113 patient
• Dabigatran vs Warfarin in Patients with AF ( non valvular)
• Publised in NEJM on Sept,2009
• Randomised to 110mg BD Pradexa,150mg BD Pradexa and warfarin
with INR goal of 2-3
• Primary effective outcome- stroke or systemic embolism
• Primary safety outcome – major bleeding
• Median follow up of 2 years

6. Primary Effective Outcome
• Lower dose was non inferior to warfarin with regard to stoke or
systemic embolism
• Lower dose showed less major bleeding ( 3.36% for warfarin and
2.71% for 110mg Pradexa)
• 150mg Prdexa- lower rate on stroke or systemic embolism compared
to warfarin ( 1.11% vs 1.69%)
• Similar rate of bleeding – intercarnial bleed more common with
warfarin and GI bleed with Pradexa 150mg
• High incidence of Dyspepsia with Pradexa (20% discontinued study
due to this)

7. Rivaroxaban (Xarelto)
• Bioavailbility – 80-100% ( dependent on food )
• Half life – 5-9hrs
• Elimination – 30-40% renal clearance unchanged
• Metabolism – via CYP 450 and 3AF
• Contra indicated in patients with Cr Clearance of < 15ml/min

8. ROCKET AF study
• Publised in NEJM on September,2011
• Rivarxaban vs warfarin in non valvular AF
• RCT – 14,264 patient randomized to receive 20mg of Rivoraxaban or
warfarin
• Primary efficacy end point – stroke or other systemic embolism
• Primary safety End point – major or non major clinically relevant
bleeding

9. Primary Efficacy Outcome
• Significant reduction in the primary end point of stroke or systemic
embolism
• 1.7% per year in rivaroxaban compared to 2.15 % per year in those
treated with warfarin

10. Primary safety end Point
• Similar rates of bleeding and adverse events compared to warfarin
• Rivaroxaban - Less ICH bleeding but increased GI bleeding
• No dyspepsia symptoms

11. Apixaban ( Eliquis)
• Bioavailability – 50%
• Half life -12hrs
• Elimination – 25-30% renal clearance
• Metabolism – Via CYP 450 and CYP3A4

12. ARISTOTLE Study
• Publised in NEJM on sept 2011
• Apixaban 5mg Bd vs warfarin ( INR 2-3 ) with AF
• Primary outcome – stroke or other systemic embolism
• Primary safety outcome – major or non major clinically relevant
bleeding

13. Primary outcome
• Apixaban compared to warfarin significantly decreased risk of stroke
and systemic embolism by 21% ( p=0.01) therefore non inferior and
superior
• Significantly reduced mortality by 11% ( p=0.047)

14. Primary safety outcome
• Reduced major bleeding by 31% ( p<0.001)
• Decreased in ICH bleeding
• No increase in GI bleeding

15. Recommendation for neuraxial anaesthesia

17. Managing the Bleed
• Scarce literature for how to manage bleed
• Currently no reversal agent