1 / 18

Journal Club

Journal Club. Jim Hoehns, Pharm.D . Edoxaban. Oral factor Xa inhibitor Bioavailability: 62% Tmax : 1-2 hrs Elimination: 50% renal Half-life: 9-11 hours. ENGAGE AF-TIMI 48. Randomized, double-blind, double-dummy trial N=21,105 patients with Afib Median follow-up: 2.8 years

colm
Download Presentation

Journal Club

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. Journal Club Jim Hoehns, Pharm.D.

  2. Edoxaban • Oral factor Xa inhibitor • Bioavailability: 62% • Tmax: 1-2 hrs • Elimination: 50% renal • Half-life: 9-11 hours

  3. ENGAGE AF-TIMI 48 • Randomized, double-blind, double-dummy trial • N=21,105 patients with Afib • Median follow-up: 2.8 years • 1393 centers; 46 countries • Treatment • “High dose” edoxaban 60mg QD • “Low dose” edoxaban 30mg QD • Warfarin INR 2.0-3.0 • Randomization: stratified according to CHADS2 score and need for a reduced dose • Dose-modification for edoxaban groups • Half-dose if any present: Clcr 30-50 ml/min, weight <60 kg, or use of verapamil, amiodarone, dronedarone

  4. ENGAGE - Methods • Inclusion criteria • Age ≥21 years • ECG tracing of Afib within previous 12 months • CHADS2 of 2 or greater • Exclusion criteria • Afib due to reversible disorder • EstClcr <30 ml/min • ACS or stroke within past 30 days • Use of dual antiplatelets • “High risk” of bleeding

  5. ENGAGE - Methods • Endpoints • Primary efficacy: time to first stroke or systemic embolism • Primary safety: major bleeding • Analysis • Modified ITT • Noninferiority: upper boundary of 97.5% CI could not exceed 1.38 vs. warfarin • Superiority testing: if met noninferiority criteria • Power: If 672 endpoints, >87% power

  6. ENGAGE - Results • 21,105 patients randomized • Reduced dose: 25% of patients • Warfarin: mean TTR 68%

  7. Observations • High study drug discontinuation rate (33%) • Similar rates among groups; would like more clarity re: symptomatic AE’s • Low-dose edoxaban 30mg QD likely not tenable • Met criteria for noninferiority • Primary endpoint: warfarin 1.5%/yr vs. low-dose 1.61%/yr • Significant increased risk of ischemic stroke vs. warfarin • HR 1.41 (95% CI: 1.19-1.67, P<0.001) • Warfarin: 1.25%/yr • Low-dose edoxaban: 1.77%/yr

  8. Summary • Edoxaban: a new factor Xa inhibitor • Will compete with dabigatran, rivaroxaban, and apixiban • “high-dose” edoxaban 60mg QD • Same lower risk of ICH and hemorrhagic stroke as other new anticoagulants • Efficacy and bleeding data look very favorable • Higher GI bleeding than warfarin

  9. Afib Trials - Comparison

  10. Afib Trials - Comparison * Significantly different (P<0.05)

More Related