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Newer oral anticoagulant 8.9.16

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Newer oral anticoagulant 8.9.16

  1. 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 08/09/2016 Dr Anup Petare. 1
  2. 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 08/09/2016 Dr Anup Petare. 2
  3. 3. 08/09/2016 Dr Anup Petare. 3
  4. 4. • Oral direct thrombin inhibitors(DTIs): Dabigatran • Oral direct factor Xa inhibitors: Rivaroxaban, Apixaban, Edoxaban. Classification of NOACs 08/09/2016 Dr Anup Petare. 4
  5. 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. 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. 08/09/2016 Dr Anup Petare. 6
  7. 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 08/09/2016 Dr Anup Petare. 7
  8. 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. 08/09/2016 Dr Anup Petare. 8
  9. 9. Edoxaban • Edoxaban non-inferior to warfarin: Prevention of stroke or systemic embolism (ENGAGE AF-TIMI); 08/09/2016 Dr Anup Petare. 9
  10. 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. 08/09/2016
  11. 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. 08/09/2016 Dr Anup Petare. 11
  12. 12. 08/09/2016 Dr Anup Petare. 12
  13. 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 08/09/2016 Dr Anup Petare. 13
  14. 14. Advantage of NOACs • Fixed-dosing • Rapid onset • No need for monitoring, • Few interactions, no interaction with food • Wider therapeutic window 08/09/2016 Dr Anup Petare. 14
  15. 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 15
  16. 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. 08/09/2016 Dr Anup Petare. 16