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New Oral Anticoagulants Are they better than what we have?

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New Oral Anticoagulants Are they better than what we have?

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  1. Welcome to Department of Medicine Grand Rounds’ series:New Oral Anticoagulants: Are they better than what we have? This program includes a video, test and evaluation modules. After viewing the video, you will be asked to complete a five question test and a brief evaluation in order to be eligible for your CME credits. The estimated time to complete this entire activity is 1 hour and 15 minutes. This program requires: WindowsMicrosoft Windows 2008 (required Desktop experience), Windows 7, Windows Vista, Windows XP, Windows 2003Microsoft Internet Explorer 7.0 or later, Firefox 3.6 or later or Google ChromeWindows Media Player 9.0 or later Media Silverlight 5.0 or laterBroadband internet connection MACMAC OS X 10.57 or laterSafari 4.0 or later or Firefox 3.6 or laterMicrosoft Silverlight 5.0 or later (viewers are prompted to install this when attempting to view a presentation)Broadband internet connection (256 Kbps or more)

  2. Welcome to Department of Medicine Grand Rounds’ series:New Oral Anticoagulants: Are they better than what we have? Geno J Merli, MD, MACP, FHM, FSVMProfessor of Medicine and SurgeryCo-Director Jefferson Vascular CenterJefferson Medical CollegeThomas Jefferson University HospitalRecorded Wednesday, September 4, 2013.This program will be available for CMEs until September 4, 2015.

  3. Objectives Following the completion of this program, participants should be able to:1. Compare and Contrast Treatment of DVT/PE with New Oral Anticoagulants2. Review Clinical Trials in Atrial Fibrillation3. Assess the Benefit of the New Oral Anticoagulants in the Hospitalized Medically ill patient 4. Review Data on the Management of Bleeding with the New Oral Anticoagulants

  4. Disclosure: Dr. Merli has revealed he provides grant/research support for BMS, Johnson & Johnson, Sanofi-aventis; he is also a scientific consultant for BMS, Johnson & Johnson and Sanofi-aventis; none of the other planners have revealed any significant commercial interests.Accreditation StatementThe Lancaster General Hospital is accredited by the Pennsylvania Medical Society to provide continuing medical education for physicians.Designation StatementThe Lancaster General Hospital designates this live activity for a maximum of 1 AMA PRA Category 1 Credit(s)™. Physicians should only claim credit commensurate with extent of their participation in the activity.Conflict of Interest StatementFaculty and all others who have the ability to control content of continuing medical education activities sponsored by Lancaster General Hospital are expected to disclose to the audience whether they do or do not have any real or apparent conflict(s) of interest or other relationships related to the content of their presentation(s).

  5. New Oral AnticoagulantsAre they better than what we have? Geno J Merli, MD, MACP, FHM, FSVM Professor of Medicine and Surgery Co-Director Jefferson Vascular Center Jefferson Medical College Thomas Jefferson University Hospital

  6. Disclosure Financial RelationshipsGeno J. Merli, MD, MACP, FHM, FSVM • J&J: Research, Scientific Advisory • Bristol-Meyer Squibb: Research, Scientific Advisory • Sanofi-Aventis: Research • Portola: Research

  7. Xa Common Pathway New Oral Agents Xa Blocker Apixaban Rivaroxaban Dabigatran Prothrombin Thrombin Clot Fibrin Fibrinogen

  8. Replacing Traditional Anticoagulants

  9. Replacing Current Agents • Treatment of DVT/PE • Non-Valvular Atrial Fibrillation • Hospitalized Medically-ill • Key Points: Black Box Warnings, Stroke, MI Risk, Major Bleeding

  10. Treatment VTEUFH, LMWH Bridge to Warfarin

  11. RE-COVER Study Dabigatran 150 mg, BID for 6 months Double Blind, Double Dummy, Non-Inferiority Schulman S, et al NEJM 2009;361:2342-2352

  12. RE-COVER Study VTE Major Bld 2.4% 1.6% Dabigatran 150 mg, BID VTE 2.1% 1.9% Warfarin INR 2-3 6 months Parenteral Anticoagulant Median 9 days Warfarin TTR= 60% Schulman S, et al NEJM 2009;361:2342-2352

  13. RE-COVER StudyIndex Events Dabi 1273 Warfarin 1266 Schulman S, et al NEJM 2009;361:2342-2352

  14. RE-COVER StudyMajor Bleeding Warfarin Dabi Schulman S, et al NEJM 2009;361:2342-2352

  15. RE-COVER • A limitation of the study is that the first dose of dabigatran, was given only after initial parenteral anticoagulation therapy had been administered for median of 9 days • “There is no data to support the use of dabigatran monotherapy for acute venous thromboembolism” Schulman S, et al NEJM 2009;361:2342-2352

  16. Rivaroxaban 15 mg, PO, BID x 3 weeks then 20mg, Qday Enoxaparin 1mg/kg/Q12hrs bridge to Warfarin INR 2-3 Open Label, Non-Inferiority trial Einstein Investigators NEJM 2010;363:2499-2510

  17. Einstein DVT Rivaroxaban 15 mg, BID x 3 wks 20 mg, Qday VTE Major Bld 2.1% 8.1% DVT Enoxaparin Warfarin INR 2-3 3.0% 8.1% 3, 6, 12 months Proximal DVT Warfarin TTR = 57.7% Einstein Investigators NEJM 2010;363:2499-2510

  18. Einstein Acute DVT StudyCauses of VTE Riva Standard Einstein Investigators NEJM 2010;363:2499-2510

  19. Einstein Acute DVT StudySafety Outcomes Riva Standard Einstein Investigators NEJM 2010;363:2499-2510

  20. Rivaroxaban 15 mg, PO, BID x 3 weeks then 20mg, Qday Enoxaparin 1mg/kg/Q12hrs bridge to Warfarin INR 2-3 Open Label, Non-Inferiority Einstein Investigators NEJM 2012;366:1287-1297

  21. Einstein PE Rivaroxaban 15 mg, BID x 3 wks 20 mg, Qday VTE Major Bld 2.1% 1.1% PE Non-Inferior Enoxaparin Warfarin INR 2-3 1.8% 2.2% 3, 6, 12 months Warfarin TTR = 62.7% Einstein-PE Investigators NEJM 2012;366:1287-1297

  22. Einstein PECauses Riva Standard Einstein Investigators NEJM 2012;366:1287-1297

  23. Einstein PEAnatomical Extent Standard Riva Einstein Investigators NEJM 2012;366:1287-1297

  24. ED - OBS History & Physical Laboratory Testing Diagnosis DVT Select Treatment Hospital Admission OBS Discharge Plan Secure Rx Communication Follow Up Acquire Med Contact PCP Phone call 24 hrs Pt Education D/C Summary Appointment 3-5 days Discharge OBS

  25. Your patient who has been on long term warfarin would like to convert to one of the new oral anticoagulant.

  26. Rivaroxaban 15 mg, PO, BID x 3 weeks then 20mg, Qday Enoxaparin 1mg/kg/Q12hrs bridge to Warfarin INR 2-3 Open Label, Non-Inferiority trial Einstein Investigators NEJM 2010;363:2499-2510

  27. Einstein DVT-Extend Rivaroxaban 20 mg, Qday VTE Major Bld 1.3% 0.7% All Rxed DVT Placebo 7.1% 0% 3, 6, 12 mo 6-12 mo Einstein Investigators NEJM 2010;363:2499-2510

  28. Double Blind, Randomized Trial Schulman S, et al NEJM 2013;368:709-718

  29. RE-MEDY VTE Major Bld Dabigatran 150 mg, BID 1.8% 0.9% VTE Warfarin INR 2-3 1.3% 1.8% 6 months Patient Rx 3 to 12 months Schulman S, et al NEJM 2013;368:709-718

  30. RE-SONATE VTE Major Bld Dabigatran 150 mg, BID 0.4% 0.3% DVT Placebo 5.6% 0% 6-18 months Patient Rx 6 to 18 months Schulman S, et al NEJM 2013;368:709-718

  31. RE-SONATE Study Schulman S, et al NEJM 2013;368:709-718

  32. Agnelli G, et al NEJM 2012;1-10

  33. AMPLIFY-EXT VTE Major Bld Apixaban 2.5 mg, BID 1.7% 0.2% 1.7% 0.1% Apixaban 5.0 mg, BID VTE 8.8% 0.5% Placebo Rx 6-12 mo 12 months Agnelli G, et al NEJM 2013;368(8):699-708

  34. AMPLIFY-EXT Apixaban 5 Placebo Apixaban 2.5 Agnelli G, et al NEJM 2013;368(8):699-708

  35. Warfarin to NOAC NOAC= New Oral Anticoagulants

  36. Non-Valvular Atrial Fibrillation

  37. Atrial Fibrillation Studies Time Therapeutic Range = TTR Modified Ahrens I, et al Thromb Haemost 2011;105

  38. Primary EndpointsAtrial Fibrillation Trials

  39. Major BleedingAtrial Fibrillation Trials

  40. Intracranial HemorrhageAtrial Fibrillation Trials

  41. Dosing SchedulesAtrial Fibrillation

  42. Atrial Fibrillation StudiesWhen should new orals be started? • RE-LY (Dabigatran) • Stroke within 14 days • Severe stroke within last 6 months • ARISTOTLE (Apixaban) • Stroke within 7 days • ROCKET-AF (Rivaroxaban) • Stroke within 14 days • Severe stroke within last 3 months Modified-Ahrens I, et al Thromb Haemost 2011;105

  43. Atrial FibrillationMy View • All FDA approved • Effective agents compared to warfarin • Patient selection for use is critical • Well managed warfarin will remain an option

  44. Medically ill Patient

  45. EXCLAIMExtended VTE Px Medically-ill Hull R, et al, Ann Intern Med 2010;153:8-18

  46. ADOPT Apixaban 2.5 mg BID Enoxaparin 40mg, Qday Goldhaber S, et al NEJM 2011;365(23):2167-2177

  47. ADOPT Study Goldhaber S, et al, NEJM, 2011; 365: 2167-2177

  48. Cohen A, et al NEJM 2013;368:513-523

  49. MAGELLAN Study Cohen A, et al NEJM 2013;368:513-523

  50. Extended VTE Prophylaxis In Medical Patients Net Clinical Benefit of Factor Xa Inhibitors EXCLAIM ADOPT MAGELLAN * p < 0.05 6 * p < 0.05 * 0.3 0.8* 3 1.7 2.1 * 2.7 Incidence (%) 0 4.1* 3 (Major Bleeding) 6 (n = 5,963) (n = 6,528) (n = 8,101) Hull R, et al, Ann Intern Med 2010;153:8-18 Cohen A, et al NEJM 2013;368:513-523 Goldhaber S, et al, NEJM, 2011; 365: 2167-2177

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