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1. Newer oral
Anticoagulants (NOACs)
Disclaimer
Any views or opinions expressed in this presentation
are solely those of the author and do not necessarily
represent those of company
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2. Need of NOACs over Vitamin K
antagonists
• Drug or food interactions
• Necessity of regular monitoring to adjust doses
• Slow onset
• Need for monitoring
• Narrow therapeutic window
• Polymorphism, Age, perioperative management
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4. • Oral direct thrombin inhibitors(DTIs): Dabigatran
• Oral direct factor Xa inhibitors: Rivaroxaban, Apixaban,
Edoxaban.
Classification of NOACs
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5. Pharmacology of NOACs
Dabigatran Rivaroxaban Apixaban Edoxaban
Mechanism Direct
thrombin
inhibitor
Direct factor Xa inhibitor
Prodrug Yes No
BA 6% 66% NF
100% F
50% 62%
Renal
excretion
80% 35% 25% 50%
Liver
metabolism
No Yes Minimal
GI
tolerability
Dyspepsia -
Dosing BD OD BD OD08/09/2016 Dr Anup Petare. 5

6. Dabigatran
• 1 st NOACs, (150mg) EMA & USFDA approved (RE-LY)
• (RE-LY) Primary efficacy endpoint (stroke and systemic
embolism): Dabigatran 150 mg BID superior to warfarin with
no significant differences in major bleedings.
• (Cf: warfarin) Reduced risk of ischaemic stroke, intracranial
haemorrhage and mortality,
Graham DJ, Reichman ME, Wernecke M, Zhang R, Southworth MR, Levenson M, Sheu TC, Mott K, Goulding MR, Houstoun M, MaCurdy TE, Worrall C, Kelman
JA.Cardiovascular, bleeding, andmortality risks in elderlymedicare patients treated with dabigatran or warfarin for non-valvular atrial fibrillation. Circulation 2015;131:157–164.
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7. Rivaroxaban
• Approved: USFDA and EMA (ROCKET AF)
• non inferior to warfarin for the prevention of stroke or
systemic embolism
• Black box warnings:
 Premature discontinuation increases the risk of
thrombotic events,
 Spinal/Epidural hematomas
 Monitor: S/S neurological impairment
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8. Apixaban
• (ARISTOTLE): significantly better than warfarin (overall
strokes—both ischaemic and haemorrhagic—and systemic
emboli)
• (AVERROES2): prematurely stopped = clear benefit in favour
of apixaban (Cf: Aspirin)
2. Connolly SJ, Eikelboom J, Joyner C, Diener HC, Hart R, Golitsyn S et al. Apixaban in patients with atrial fibrillation. N Engl J Med 2011;364:806–817.
1. Granger CB, Alexander JH, McMurray JJ, Lopes RD, Hylek EM, Hanna M, Al-Khalidi HR, Ansell J, Atar D, Avezum A, Bahit MC, Diaz R, Easton JD, Ezekowitz
JA, Flaker G, Garcia D, Geraldes M, Gersh BJ, Golitsyn S, Goto S, Hermosillo AG, Hohnloser SH, Horowitz J, Mohan P, Jansky P, Lewis BS, Lopez-Sendon JL, Pais P,
Parkhomenko A, Verheugt FW, Zhu J, Wallentin L; ARISTOTL Committees and Investigators. Apixaban vs. warfarin in patients with atrial fibrillation. N Engl J Med
2011;365:981–992.
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9. Edoxaban
• Edoxaban non-inferior to warfarin: Prevention of stroke or
systemic embolism (ENGAGE AF-TIMI);
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10. Dr Anup Petare. 10Wassef A, Butcher K. Novel oral anticoagulant management issues for the stroke clinician.
Int J Stroke. 2016 Jul 27. pii: 1747493016660100.
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11. Comparison between NOACs
Ruff CT, Giugliano RP, Braunwald E, Hoffman EB, Deenadayalu N, Ezekowitz MD, Camm AJ, Weitz JI, Lewis BS, Parkhomenko A, Yamashita T, Antman
EM.Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomised trials. Lancet 2014;
383:955–962.
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13. High risk of stroke
(high CHADS-VASC score)
Dabigatran 150 mg BID
Previous stroke Rivaroxaban 20 mg QD
High risk of bleeding or previous
life-threatening bleedings
Dabigatran 110 mg BID
Apixaban 5 mg BID
Dyspepsia Rivaroxaban 20 mg QD
Apixaban 5 mg BID
GI bleeding Apixaban 5 mg BID
Medication compliance problems Rivaroxaban 20 mg QD
Elderly (≥80 years) and impaired
renal function
Apixaban 2.5 mg BID
Choice of NOACs
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14. Advantage of NOACs
• Fixed-dosing
• Rapid onset
• No need for monitoring,
• Few interactions, no interaction with food
• Wider therapeutic window
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15. Limitations of NOACs
• Lack of an effective antidote
• Cost
• Vitamin K Antagonists 1st line anticoagulant: Mechanical
heart valves or RHD and with severe renal insufficiency,
• ESC guidelines doesn’t recommend rivaroxaban and
apixaban ( RHD, Mechanical heart valve, Severe renal
insufficiency)
Camm AJ, Lip GY, De Caterina R, Savelieva I, Atar D, Hohnloser SH et al. Focused update of the ESC Guidelines for the management of atrial
fibrillation: an update of the 2010 ESC Guidelines for the management of atrial fibrillation. Developed with the special contribution of the European
Heart Rhythm Association. Europace 2012;14:1385–1413.08/09/2016 Dr Anup Petare. 15
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16. Conclusion
• NOACs have a favourable balance between efficacy and
safety compared with VKAs
• Individualized anticoagulant treatment: Age, RFT,
concomitant treatment
• NOACs future depends upon clinical experience, patients’
tolerance to these drugs, novel data from further studies,
reimbursement policies, and other market forces.
• Further research is underway: Monitor anticoagulant effect,
antidote.
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