Doacs by dr hafeesh fazulu
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This document discusses direct oral anticoagulants (DOACs) including their classification, mechanisms of action, drugs, indications, dosages, and reversal agents. It covers the management of bleeding in patients taking DOACs and the perioperative management of patients receiving anticoagulants. It also discusses oral anticoagulant use in patients with atrial fibrillation and chronic kidney disease, focusing on the renal excretion of DOACs.
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Doacs by dr hafeesh fazulu
- 1. DOAC’S Dr Hafeesh Fazulu DM Cardiology Resident Pushpagiri Heart Institute, Thiruvalla,Kerala.
- 2. Outline • DOACS – Classification,Drugs,Indications, MOA, Dosages, Reversal agents etc. • Management of bleeding in patients receiving direct oral anticoagulants • Perioperative management of patients receiving anticoagulants • Oral anticoagulants in patients with atrial fibrillation and chronic kidney disease (August 2019 UPDATE)
- 5. History • The drug that was in use for 70 years – WARFARIN • Approved in 1941 !! • Narrow therapeutic window • Regular Blood testing & Dosage adjustments • Unpredictable pharmacokinetics and Pharmacodynamics
- 7. Change in Terminology –NOACS to DOACS
- 8. Classification • DIRECT IIa Inhibitors • ORAL • Dabigatran • PARENTRAL • Bivalirudin • Argatroban • Desirudin • DIRECT Xa Inhibitors • ORAL • Rivaroxaban • Apixaban • Edoxaban • Betrixaban
- 9. Sites of Action Direct Xa Inhibitor Direct IIa Inhibitor
- 10. Direct Thrombin (IIa) Inhibtors • XIMELAGATRAN – was first Direct thrombin inhibitor • Withdrawn from market in February 2006 due to severe Hepatotoxicity and major adverse cardiovascular events
- 11. Dabigatran (PRADAXA) • Approved in 2010 • DABIGATRAN EXEXITATE – prodrug • Converted to Dabigatran • Bioavaiability – 6.5 % • Maximium Anticoagulant effect within – 2-3 hours • 80% excreted by KIDNEYS • Cr Cl 15-30 : 75mg BD • Avoid if Cr Cl <15 • Half Life – 12-17 hours • BD Dosing • Trial – RE-LY Study • Non-inferior to warfarin • Similar rates of bleeding • LOWER stroke rate & systemic embolism • Interacts • Rifampin • VERAPAMIL, Ketoconazole • OBESITY • Avoid if BMI >40 • Weight > 120 kg
- 14. Parentral Direct Thrombin Inhibitors • Bivalirudin • Argatroban • Desirudin
- 15. Factor Xa Inhibitors – The “Xa-ban’s” • Better to inhibit Xa than IIa ? Factor IIa has more functions other than Coagulation Activates procoagulant factors V, VIII XI XIII Activates platelets • One molecule of Xa will cleave 1000 molecules of prothrombin to Thrombin (IIa)
- 16. RIVAROXABAN (XARELTO) • Approved in 2011 • ROCKET-AF Trial • Non-inferior to warfarin • Similar rates of bleeding • Less fatal bleeding with Rivaroxaban • Half life – 5-9 hrs • Dual mode ELIMINATION • Kidneys – 1/3 • Liver – 2/3
- 17. • DOSE • Stroke prevention in AF • 20mg OD (Cr Cl >50) • 15mg OD (Cr Cl <50) • VTE Prophylaxis – 10mg with food • VTE Treatment & Sec. Prevention – • 15mg BD x 21 days • 20mg OD x continue
- 18. APIXABAN (ELIQUIS) • Half life – 12 hrs • DOSE • Stroke prevention in AF • 5mg BD (Cr Cl >50) • 2.5mg BD (age >80, Wt <60kg, Creat>1.5) • VTE Prophylaxis – • 2.5mg BD x 12-35days • VTE Treatment & Sec. Prevention – • 10mg BD x 7days • Followed by 5mg BD
- 19. • AVERROES Trial • ARISTOTLE Trial • Superior to Wafarin • Reduced stroke risk by 21% • Reduced Bleeding risk by 31% • FIRST DOAC to show reduced risk of death due to any cause by 11%
- 20. EDOXABAN • Half Life – 10-14 hours • DOSE • VTE Treatment • Given after 5-10 days of parentral anticoagulant • 30/60mg OD
- 21. • ENGAGE AF TIMI 48 Trial • Noninferior to warfarin • Reduced stroke risk by 21% • Reduced Bleeding risk by 20% (60mg OD dosing) • Reduced Bleeding risk by 53% (30mg OD dosing) –still noninferior to warfarin
- 22. BETRIXABAN • Half life 19-27 hrs • DOSE • Only for Prevention of VTE • 160mg on Day 1 • Followed by 80mg OD x 35-42 days
- 24. Switching Drugs
- 25. Switching from Warfarin to DOAC Resolution of Warfarin effects may take several days
- 26. Switching fromDOAC to Warfarin Full effects of VKA do not occur for first few days even though INR is prolonged.
- 28. Switching from one DOAC to another DOAC • Start the second DOAC when the next dose of the first DOAC would have been due; do not overlap.
- 30. Settings in which Heparin/Warfarin preferred over DOAC • Prosthetic Heart Valves – greater risk of Valve thrombosis • Pregnancy – Lack of experience with DOAC • LMWH preferred pregnancy • Renal impairment – • Severe Liver Disease - • APLA – few data on the efficacy of DOAC in APLA • H/O GI Bleeding • Cost
- 31. Management of bleeding in patients receiving direct oral anticoagulants
- 32. Reversal agent for Thrombin inhibitors • IDARUCIZUMAB • 5gm IV • Cost – 2.4 lakhs
- 33. Reversal agent for Xa Inhibitors • ANDEXANET ALPHA • Cost - 41.4 Lakhs
- 37. Perioperative management of patients receiving anticoagulants
- 39. Oral anticoagulants in patients with atrial fibrillation and chronic kidney disease (August 2019)
- 40. Renal excretion of DOACS
- 43. THANK YOU
Editor's Notes
- h
- PCC – Prothombin Complex concentrates Unactivated prothrombin complex concentrates (PCCs) and activated PCCs (aPCCs) both contain clotting factors purified from human plasma. They differ in their composition (eg, 3-factor PCCs contain factors II, IX, and X; 4-factor PCCs contain factors II, IX, X, and VII) Antifibrinolytics – FFP – no evidence to support the use of FFP for DOAC associated bleeding