Journal club
Download
1 / 18

Journal Club - PowerPoint PPT Presentation


  • 151 Views
  • Uploaded on

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

loader
I am the owner, or an agent authorized to act on behalf of the owner, of the copyrighted work described.
capcha
Download Presentation

PowerPoint Slideshow about ' Journal Club' - rhiannon-reese


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.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.


- - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - -
Presentation Transcript
Journal club

Journal Club

Jim Hoehns, Pharm.D.


Edoxaban
Edoxaban

  • Oral factor Xa inhibitor

  • Bioavailability: 62%

  • Tmax: 1-2 hrs

  • Elimination: 50% renal

  • Half-life: 9-11 hours


Engage af timi 48
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


Engage methods
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


Engage methods1
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


Engage results
ENGAGE - Results

  • 21,105 patients randomized

  • Reduced dose: 25% of patients

  • Warfarin: mean TTR 68%


Observations
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


Summary
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


Afib trials comparison
Afib Trials - Comparison


Afib trials comparison1
Afib Trials - Comparison

* Significantly different (P<0.05)


ad