1 / 26

New Oral Anticoagulants: A Review

New Oral Anticoagulants: A Review . Babak Moini, MD Veterans Affairs Hospital Noon Lecture S eries. Acknowledgment: . Some of the slides were borrowed from Amanda Miller Phar.D. Case1.

Download Presentation

New Oral Anticoagulants: A Review

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript


  1. New Oral Anticoagulants: A Review Babak Moini, MD Veterans Affairs Hospital Noon Lecture Series

  2. Acknowledgment: • Some of the slides were borrowed from Amanda Miller Phar.D.

  3. Case1 • 68 male with hx of DM, CHF and prior ischemic CVA admitted for new afib. He has a hx of non-compliance. • CHADs2: 4. • Which anticoagulant to send him home with?

  4. Oral Anticoagulants Available in US

  5. Mechanism of Action

  6. rivaroxaban apixaban dabigatran http://www.healio.com/~/media/Images/News/Online/Orthopedics/2009/12_December/01/79_fig_400_307_57368.gif

  7. Pharmacology:

  8. Indications: US Not yet approved: Rivaroxaban for prophylaxis of DVT in medically ill patients (MAGELLAN). Rivaroxaban vs Enoxaparin. NI < 30 days, superior at 35 days.

  9. Usual Dosing (A fib)

  10. Usual Dosing (VTE) • Only FDA-approved agent = rivaroxaban • VTE Prophylaxis (knee/hip surgery) • 10mg once daily (up to 35 days) • No renal dose (CrCl < 30 ml/min  avoid) • VTE Treatment: • 15 mg BID x 3 weeks then 20mg daily • No renal dose (CrCl < 30 ml/min  avoid)

  11. Perioperative Recommendations Dabigatran PI, Blood 2012;119:3016-23

  12. Major Side Effects: • Bleeding: varied definition in each study. • GI • ICH • Major (drop in Hgb by 2, life threatening). • Dabigatran: • Pills are made in acidic content, hence has 20% rate of GI side effects. • ? Observed increase risk of GI bleeding.

  13. Monitoring Levels: • Coumadin: INR • New Oral anticoagulants: no standardized studies. No accurate quantitative measures. • Dabigatran: ECT, Thrombin clotting time • Rivaroxaban: special anti-Xa activity • Abixaban special anti-Xa activity

  14. Drug-Drug Interactions: • No where as severe as with Warfarin. • Dabigatran: P-glycoprotein, pro-drug. • Needs acidic environment, avoid co-administration with PPI. • Rivaroxaban: CYP-450 and P-glycoprotein. • Caution with dual inhibitors (Ketoconazole, Itroconazole, Clarithromycin). • No dose adjustments needed. • Abixaban: CYP3A4 and P-glycoprotein. • Decrease dose to 2.5mg bid in dual inhibitors.

  15. Switching To/From Warfarin

  16. Treatment of Bleeding: • No evidence based guidelines. • Remember that unlike Coumadin, the new OAC will continuously bind to factor Xa or thrombin, hence making FFP less useful. • Current available Rx for life threatening active bleeding: based on case reports. • Factor VII • PCC: 3 and 4 factor concentrates. • HD: only for Dabigatran. Large volume of distribution. • Charcoal Gonsalves Et al. Mayo Clinic Proc. 5-2013

  17. Trials vs Warfarin for A Fib * Dose reductions for renal impairment

  18. Trials vs Warfarin for A fib

  19. Major Findings: • RELY • Dabigatran110mg NI to Warfarin (1.53% vs 1.69%). • Dabigatran150mg superior to Warfarin ONLY if compared with sub-optimal INR subgroup (1.11 % vs 1.69%). • Major bleeding less with 110mg (2.71 vs 3.11%). • ROCKET-AF • Rivaroxaban NI to Warfarin (2.1% vs 2.4%) • Less ICH or fatal bleeding (0.4% vs 0.8% ) • ARISTOTLE: • Abixaban Superior to Warfarin (1.27% vs 1.6% ) • Less Major bleeding (1.4% vs 2.1% )

  20. Key Safety Endpoints (% per year) • *: Primary safety endpoint: • RE-LY  major hemorrhage • ROCKET-AF  major + non-major clinically relevant bleeding • ARISTOTLE  ISTH (Int Soc Thromosis & Hemostasis) major bleeding

  21. Figure 3 Forest plot for (A) major bleeding, (B) intracranial bleeding, and (C) gastrointestinal bleeding, new oral anticoagulants (NOA) versus warfarin in patients with AF. http://dx.doi.org/10.1016/j.amjcard.2012.03.049

  22. Quick Review of Evidence- Based Medicine: • I • A: Systemic review of multiple RCTs / multiple RTCs • B: High quality single RTC • II: • A: Systemic review of cohort studies • B: High quality cohort studie(s) • III: • Systemic review of Case/Control studies / Case Control studies • IV • Case reports • IV • Expert opinion

  23. Chest 2012; 141:e531S-e575S Stroke 2012;43: 3442-3453 OAC = oral anticoagulation

  24. New OAC: • Pros: • Easy administration • Immediate effect • Much less food and drug interactions • One dose fits all • The names sound so much cooler than WARFARIN. • Cons: • Expensive • Inability to monitor compliance • Short duration: loss of effect with a single missed dose • No safe/reliable antidotes • ? Bleeding. Observational bias vs real difference. • Renal dosing

  25. Take home message: • Coumadin still remains the drug of choice for many patients due to cost, past experience and known side effects. • Many new OAC are in the pipeline, expect a barrage of pharma bombardments, must remain objective as many of the studies have different inclusion/exclusion criteria, definition of end points and side effects. • Each patient may benefit from a different type of OAC based on comorbidities and drug side effect profile. • Watch out for recall bias with the new OAC among your own colleagues. • Patient compliance is a major factor: remember with the new OAC one missed dose means a lot!

  26. The End!

More Related