NOACPraneel Kumar

Fibrinogen Fibrin

Common Pathway

Thrombin

Xa

Prothrombin

Clot

Xa

BlockerApixaban

Rivaroxaban

Dabigatran

New Oral Agents

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

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

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)

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

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

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

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

Apixaban ( Eliquis)

• Bioavailability – 50%

• Half life -12hrs

• Elimination – 25-30% renal clearance

• Metabolism – Via CYP 450 and CYP3A4

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

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)

Primary safety outcome

• Reduced major bleeding by 31% ( p<0.001)

• Decreased in ICH bleeding

• No increase in GI bleeding

Recommendation for neuraxial anaesthesia

Managing the Bleed

• Scarce literature for how to manage bleed

• Currently no reversal agent