Downloaded 14 times
Uploaded byAthens Heart Center & Specialty Clinics
Dr. Ganasani
Sreeni Gangasani is a cardiologist who specializes in general cardiology, echocardiography, nuclear cardiology, and preventive cardiology. He received his medical degree and residency training in India and completed fellowship training at William Beaumont Hospital. The document discusses newer oral anticoagulants (NOACs) including dabigatran, rivaroxaban, apixaban, and edoxaban which are alternatives to warfarin for treating and preventing blood clots. It provides details on their mechanisms of action, pharmacokinetics, FDA-approved indications, and practical considerations for use.
More Related Content
Dr. Ganasani
- 1. Sreeni Gangasani, M.D. •Cardiologist at Gwinnett Heart Specialists • American Board of Internal Medicine Cardiovascular Disease • American Board of Internal Medicine Internal Medicine • AOA Board of Internal Medicine Cardiology • Special interests include general Cardiology, Echocardiography, Nuclear, Preventive Cardiology Medical School: Kurnool Medical College Residency: William Beaumont Hospital Fellowship: William Beaumont Hospital
- 2. Tailoring NOAC’s foryour individual patient Sreeni Gangasani MD, FACC
- 3. • 1. Wehate sleeping. 2. We have enjoyed our life in childhood. 3. We can't live without tension. 4. We want to have a disturbed life. 5. We want to take revenge on ourselves. 6. We love dreaming about diseases . 7. We love to work on holidays. 8. We can't live without mobile hooked on our ears even in the bathroom . 9.When we make money its already too late6/12/2015 Gwinnett Heart Specialists 9 reasons why we chose Medicine as a profession:
- 4. • Which oneis the newest of direct Factor X inhibitors ? • A) Darbigatran • B) Edoxaban • C) Rivaraxoban • D) Epixaban • E) Betrixaban 6/12/2015 Gwinnett Heart Specialists Question 1
- 6.
- 7. • Prevention andtreatment of venous thromboembolism (VTE) • Stroke prophylaxis in non-valvular atrial fibrillation (AF), Newer Oral Anticoagulants Gwinnett Heart Specialists6/12/2015
- 8. • Low-molecular-weight heparin(LMWH) or unfractionated heparin (UFH) is used initially in the treatment of acute VTE or A fib, followed by long-term vitamin K antagonist (VKA) therapy. • For stroke prophylaxis in AF, long-term anticoagulation with the VKA warfarin is the standard of care Traditional care Gwinnett Heart Specialists6/12/2015
- 9. • Inter patientvariability with regard to clinical response because of genetic polymorphisms, particularly upon initiating therapy. • Drug-drug and drug-food interactions necessitate more frequent monitoring of international normalized ratio (INR) and may complicate management. • Major and non–major bleeding events, • Supra and Sub therapeutic INRs management • In older patients, warfarin is the most common cause of drug-related emergency hospitalization Problems with Warfarin Gwinnett Heart Specialists6/12/2015
- 10. 6/12/2015 Gwinnett HeartSpecialists
- 11.
- 12. • Dabigatran andRivaroxaban and Apixaban Edoxaban have successfully completed phase III trials for acute VTE treatment, Prophylaxis and are currently approved for the reduction of risk of stroke and systemic embolism in patients with non-valvular AF Newer Anticoagulants Gwinnett Heart Specialists6/12/2015
- 13. • Direct thrombininhibitors - dabigatran( Pradaxa) Factor IIa Inhibitors Gwinnett Heart Specialists6/12/2015
- 14. • The pro-drugdabigatran etexilate is converted completely to active dabigatran • Terminal elimination t½ of 14–17 hours • Bioavailability of 3.5–6.5% • No food interactions • Eliminated mainly by renal excretion (80%) Dabigatran (Pradaxa) Stangier et al. J Clin Pharmacol 2005; Liesenfeld et al. Br J Clin Pharmacol 2006; Stangier et al. Br J Clin Pharmacol 2007 Gwinnett Heart Specialists6/12/2015
- 15. • Must bestored in the original blister pack with desiccant and not crushed. 6/12/2015 Gwinnett Heart Specialists Dabigatran
- 16. VIIa Xa IXa XIa XIIa Direct Factor Xainhibition Tissue factor Fibrinogen Fibrin clot Factor II (prothrombin) Rivaroxaban Apixaban YM150 Edoxaban Betrixaban TAK 442 × Gwinnett Heart Specialists6/12/2015
- 17. Direct Factor XaInhibitors Rivaroxaban (Xarelto) Apixaban (Eliquis) Edoxaban( Savaysa) Gwinnett Heart Specialists6/12/2015
- 18. Rivaroxaban: oral directFactor Xa inhibitor (Xarelto) • Predictable pharmacology • High bioavailability • Low risk of drug– drug interactions • Fixed dose • No requirement for monitoring Perzborn et al. 2005; Kubitza et al. 2005; 2006; 2007; Roehrig et al, 2005 Rivaroxaban® – rivaroxaban N N O N H O S Cl O O O Gwinnett Heart Specialists 6/12/2015
- 19. Apixaban(Eliquis) • Oral, direct,selective factor Xa inhibitor • Produces concentration-dependent anticoagulation • No formation of reactive intermediates • No organ toxicity or LFT abnormalities in chronic toxicology studies • Low likelihood of drug interactions or QTc prolongation • Good oral bioavailability • No food effect • Balanced elimination (~25% renal) • Half-life ~12 hrs He et al., ASH, 2006, Lassen, et al ASH, 2006 N N NO N O NH2 O O Gwinnett Heart Specialists6/12/2015
- 20. Edoxaban( Savaysa) • Half-life:6-11hrs • Dosing 30 or 60 mg orally once daily • Absorption is unaffected by food • Renally excreted • Substrate for P glycoprotein • Reduced efficacy in nonvalvular atrial fibrillation in patients with a high creatinine clearance (CrCL >95 mL/minute)6/12/2015 Gwinnett Heart Specialists
- 21. • Laboratory testingshould include • Prothrombin time (PT) • Activated partial thromboplastin time (aPTT), • Serum creatinine, as a baseline and for potential dose adjustment in the event of renal insufficiency. 6/12/2015 Gwinnett Heart Specialists Testing before starting NOAC
- 22. • NOAC arecontraindicated in what valvular heart disease conditions ? • A) Moderate mitral regurgitation • B) Mild Aortic stenosis • C) Moderate to severe tricuspid regurgitation • D) Prosthetic mechanical aortic valve • E)Bicuspid aortic valve with minimal aortic regurgitation6/12/2015 Gwinnett Heart Specialists Question 2
- 24. • Many ofthe major clinical trials subsequent meta-analyses have excluded patients with • prosthetic heart valves, • with mitral stenosis, • with decompensated valvular heart disease who were likely to require valve replacement in the near future. • Based on these studies, the newer anticoagulants should not be prescribed for 6/12/2015 Gwinnett Heart Specialists Valvular heart disease and NAC
- 25. • Which ofthe NOAC is approved for use in ESRD? • A) Epixaban • B) rivaroxoban • C) Edoxaban • D) None of the above 6/12/2015 Gwinnett Heart Specialists Question 3
- 27. Renal Insufficiency Gwinnett HeartSpecialists6/12/2015
- 28. Time to fullyactive: 5 days vs 2-3 hrs Time to being out of system :5-7 days vs 24-48hrs Cost : NOAC more expensive(About $200/month) Safety: • Same risk of major bleeding, but lower risk of bleeds into the head with NOAC Differences between VKA vs NOAC Gwinnett Heart Specialists6/12/2015
- 29. Factor Warfarin Enoxaparin (LMWH) Dabigatran etexilate Rivaroxaba n Apixaban Routine laboratory monitoring required X Antidote available XX Dose adjustment for renal insufficienc y X X X X Rapid onset and offset of action X X X Comparison of key considerations for new oral anticoagulants Factor Warfari n Enoxa parin (LMW H) Dabigatran Rivaroxaban Apixaban Routine laboratory monitoring required X Antidote available X X Dose adjustment for renal insufficiency X X X X Rapid onset and offset of action X X X Gwinnett Heart Specialists6/12/2015
- 30. Comparison of theNOAC for DVT and PE Apixaban Dabigatran Rivaroxaban Started immediately with Dx DVT or PE yes no yes Dosing BID BID QD Excreted through the kidney 25% 80% 33% Efficacy c/w warfarin (recurrent DVT or PE) same same same Safety c/w warfarin in respect to bleeding better same same/better Reversal agent available for major bleeding none none none FDA approved for DVT/PE treatment yes yes yes Gwinnett Heart Specialists6/12/2015
- 31. • 68% relativerisk (RR) reduction of ischemic stroke compared with placebo; • Aspirin has a less-robust RR reduction of 21% compared with placebo Warfarin Gwinnett Heart Specialists6/12/2015
- 32.
- 33. 6/12/2015 Gwinnett HeartSpecialists
- 34. 6/12/2015 Gwinnett HeartSpecialists
- 35. • Difficult achievingstable anti-coagulation • Drugs proven to cause INR fluctuations • Better compliance with once a day than bid (rivaroxiban vs dabigatran/apixaban) Who should switch? Gwinnett Heart Specialists6/12/2015
- 36. • GI bleeds(increased risk with dabigatran and rivaroxiban) either stay on VKA or apixaban • Previous acute coronary syndromes??? Conflicting data with dabigatran • Populations excluded from trials: pediatric, pregnant patients, prosthetic valves (Re- ALIGN a negative trial) Who should NOT switch? Gwinnett Heart Specialists6/12/2015
- 37. • When tostop NOACs? • Risk of stroke when off ACs • Duration off vs CHADS2 score How to deal with Surgery? Gwinnett Heart Specialists6/12/2015
- 38. How to dealwith Surgery? Gwinnett Heart Specialists6/12/2015
- 39. • Depends onCHADS2 • For CHADS2 of ≥3 use bridge with lovenox or IV Heparin Risk of stroke off Anticoagulants Gwinnett Heart Specialists6/12/2015
- 40. Risk Scores Gwinnett HeartSpecialists6/12/2015
- 41. Stroke Risk Gwinnett HeartSpecialists6/12/2015
- 42. • NOACs discontinuedand procedure schedules 1-2 days later….if possible • Risk of bleeding vs risk of delaying surgery How to deal with Urgent Surgery? Gwinnett Heart Specialists6/12/2015
- 43. • Which ofthe NOAC is class B in Pregnancy? • A) Endoxaban • B) Epixaban • C) Darbigatran • D)Rivaraxoban 6/12/2015 Gwinnett Heart Specialists Question 4
- 44. • Eliquis: ClassB ( No adverse effects demonstrated but not enough data) • Xarelto: Class C ( Use with caution) • Pradaxa : Class C • Lactation: Not indicated(safety unknown) 6/12/2015 Gwinnett Heart Specialists Pregnancy and Lactation
- 45. • Ecarin clottingtime has shown to be a reliable assay to assess coagulation in patients taking dabigatran etexilate • Availability of this assay is limited . • Prothrombin time assays may be useful for assessing coagulation in patients receiving rivaroxaban or apixaban (dilute prothrombin time), but because of a lack of standardization, as is the case with INR, results may be difficult to interpret. • Anti–factor Xa assays used for nonroutine monitoring of LMWHs may prove to be the best method to monitor rivaroxaban or apixaban Laboratory monitoring Gwinnett Heart Specialists6/12/2015
- 46. • The neworal anticoagulants do not have specific antidotes • For non–major bleeding events, temporary cessation • Activated prothrombin complex concentrates (PCCs) and recombinant factor VII have been explored in early studies as reversal agents for the new anticoagulants, but data are limited Management of bleeding events Gwinnett Heart Specialists6/12/2015
- 47. • A studyin healthy human subjects demonstrated that 4-factor PCCs that are available in Europe immediately and completely reverse the effect of rivaroxaban, but they did not have any influence on dabigatran at the dose studied. • Recombinant factor Xa is currently being explored as a reversal agent for factor Xa inhibitors Management of bleeding events Gwinnett Heart Specialists6/12/2015
- 48. • Emergency dialysismay be considered • Partially dialyzable, • Maintain renal perfusion with intravenous fluids. • Need to develop protocols for institution for major bleeds Darbitrigan Gwinnett Heart Specialists6/12/2015
- 49.
- 50. • Name: HusbandSymbol: Hb • Atomic Weight: -Light when first found... -tends to get heavier over the years with time. • Physical Properties : - Boils at any time with inlaws - Melts if sees other women - Very Bitter if questioned • Chemical Properties : - Very Reactive - Highly Unstable - Possess Strong resistance to Gold, Silver,Diamond, Platinum, Credit cards&Cheque books • Occurrence : - Mostly found in front of the TV 6/12/2015 Gwinnett Heart Specialists A new metal is added to chemistry:
- 51. • Which NOACshould not be used when Cr Cl is over 95? • A) Endoxoban • B) Epixaban • C) rivaraxoban • D) Darbigatran 6/12/2015 Gwinnett Heart Specialists Question 5:
- 52. • No datahead to head between agents • Insurance • Familiarity with agent • Availability of samples • Side effect profile6/12/2015 Gwinnett Heart Specialists NOAC Agent of choice
- 53. 6/12/2015 Gwinnett HeartSpecialists
- 54. 6/12/2015 Gwinnett HeartSpecialists