1. G U I G L I A N O R P, E T A L . T H E N E W E N G L A N D
J O U N R A L O F M E D I C I N E . 2 0 1 3 . 3 6 9 ( 2 2 ) : 2 0 9 3 - 1 0 4
EDOXABAN VS. WARFARIN IN
PATIENTS WITH ATRIAL
FIBRILLATION
PRESENTED BY:
THU NGUYEN
PHARM.D CANDIDATE, 2018
TNGUYEN36@STUDENT.TOURO.EDU
3. BACKGROUND
ENGAGE AF-TIMI 48
Add to the growing body of evidence favoring
NOACs in the prevention of stroke in pt with nonval
AF
For many years, lack of a rapid and safe reversal agent
for NOACs has ltd clinical use of these agents in AF
pts given the concern for irreversible bleed
Major points
Given the poor TTR and difficulty in dosing
warfarin, NOACs – better alternative for
preventing stroke and decreasing mortality in
AF pts.
ARISTOLE, RE-LY,
ROCKET AF have had
favored results
Recent registry-based study of 5,210 pts
with AF on Warfarin found only 59% of
all INR values to be within a therapeutic
range
Clinical question
Among pts with nonvalvular A.Fib, how does Edoxaban, compare with Warfarin in
preventing stroke or systemic embolism?
4. Design
Multi-center
double-blind
double-dummy
RCT
N = 21,105
-High dose Edoxaban
- Low dose Edoxaban
- Warfarin
Setting:
1,393 centers in 46
countries
Enrollment:
Nov 2008 – Nov 2010Median follow-up:
2.8 years
-Primary endpoint: stroke or
systemic embolism
-Principal safety endpoint:
major bleeding
Analysis: Non-
inferiority and
modified ITT
Primary outcome:
- Time to first
adjudicated stroke or
systemic embolic event
- Stroke, systemic
embolic event, or death
from CV causes
5. POPULATION
Inclusion Criteria
Pts >21 y/o with documented AF w/i 12
months prior to randomization
Score of >2 on CHADS2
Anticoag therapy planned for the duration
of the trial
Exclusion Criteria
AF d/t reversal disorder
CrCl < 30ml/min
Use of dual anti-plt therapy
Moderate-to-severe mitral stenosis
Other indications for anticoag therapy
ACS
Coronary revascularization
Stroke w/i 30 days before randomization
Inability to adhere to study procedure
6. BASELINE
CHARACTERISTICS
Demographics:
Median age: 72
Female: 37.5%
Cardiac Hx
-Paroxysmal AF: 25.3%
-Qualifying RF: Age>75, Prior
stroke/TIA; CHF; DM; HTN
requiring treatment.
- CHADS2 score: <3 (77.4%)
Dose reduction at randomization:
-CrCl <50ml/min
- Weight <60kg
- Use of Verapamil/quinidine
Medical Hx
- Previous use of vit. K
antagonists for >60 days.
- Aspirin: 29.3%
Thienopyridine: 2.3%
- Amiodarone: 11.8%
- Digoxin or digitalis
preparation: 30.9%
Warfari
n group
Intervention
7. INTERVENTIONS
Patients were randomly assigned in a 1:1:1 ratio to
receive warfarin (dose-adjusted to INR of 2-3), High -
dose edoxaban or low-dose edoxaban
For patients receiving either dose of Edoxaban, the dose
was halved if any of the following characteristics were
present at time of randomization or during the study:
CrCl of 30-50 ml/min
Body weight of 60kg or less OR concomitant use of
Verapamil or Quinidine
8. OUTCOMES
Primary
Outcomes
Rate to first adjudicated
stroke or systemic
embolic event
Modified ITT (1.5% vs.
1.18% vs. 1.61% of
pt/years) – P=0.005
ITT (1.8% vs. 1.57% vs.
2.04% of pt/yr) – P=0.1
Secondary
Outcomes
Stroke, systemic
embolic event, or
death from CV causes
(including bleeding)
Major adverse CV events
(MI, stroke, systemic embolic
event, or death from CV
causes)
Stroke, systemic
embolic event, or
death from any
cause.
Adverse
Events
Adjudicated major
bleeding during
treatment
3.43% vs. 2.75% vs. 1.61% of pt/year
(P ≤ 0.001 and P ≤ 0.001 )
9. CRITICISMS
-Hi-dose Edoxaban
met criteria for
superiority over
Warfarin for the
primary endpoint
during treatment
period
-During the pre-
specified superiority
analysis for efficacy
performed in the
ITT population over
the entire study
period.
- Unclear whether
this regimen is truly
more effacious than
Warfarin
Treatment
interruptions more
frequent in the
Warfarin group than
in either Edoxaban
group, potentially
overestimating the
treatment effect of
Edoxaban
10. FUNDING
• Study funded by Daichi Sankyo Pharma Development (Edoxaban Mfr)
• Authors with multiple ties to industry and receiving funding from Mfr of Edoxaban
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Editor's Notes
As one of the largest fee-only investment managers in the state of Georgia, our job is to help you chart out your own course to retirement. Here, presenters should place their credibility statement, education, title, and/or years of experience.
This slide lays out the overall objective of the presentation; which is how to achieve or start working towards a “successful retirement”. It starts with a “written financial plan”, and moves clock-wise – all centered around the main goal. On this continuum, buttons can be added or removed, depending upon the financial professional giving the presentation.
A successful retirement plan has many moving parts and each of them must serve a unique function in carrying you to retirement. Regardless of your situation, the journey to retirement is likely dotted with some storms and choppy seas along the way.
Here, I have laid out what I believe to be the very basic principles necessary for any successful retirement plan.
This slide begins with “written financial plan”, which is a critical step in being able to navigate any path towards retirement.
In any financial presentation, it is important to help the audience establish and understand their goals. Understanding this process is to “chart the course” for each individual in the room. Every financial professional should have a different take on this, but typically there will be between two and three planning phases for a given audience/client. If three goals are needed, you can simply add to the graphic.
Financial professionals should feel free to customize the language labeled in bullet points for each phase.
Note: To add another goal to the SmartArt graphic on this slide, click in the graphic to activate the SmartArt text pane. Click at the end of the last bullet in the pane, press Enter, and the press Shift+Tab to start another first-level bullet. A new section will be added to the graphic automatically and existing elements automatically resized. To add the items under the new goal, press Enter in the text pane to create a new paragraph and then press Tab to demote the new paragraph to the second level.
This slide illustrates more of a timeline or progression for completing major savings during the course of an investor’s lifetime. The slide serves to answer the age-old question, “Where am I now and where do I start?”.
This is a visual that should be discussed with the audience. It describes the relationship between risk and reward. Notice that the relationship between the two is very familiar; the higher the risk an investment carries, the higher your potential payoff will be. Likewise, lower risk investments carry little or no reward. This slide is an extremely simple explanation of the risks involved in different investments, but it is important to understand the basics before you move forward.
As you’re accumulating, this is a logical order in which to contribute to your commonly-used retirement savings vehicles.
Financial professionals should feel free to customize their own hierarchy so that the audience has a clear, visual understanding of how investment “blocks” should build on each other.
“The Bucket Slide”
The bucket slide helps investors think about asset allocation (a complex concept) in a simplified, easy to understand graphic. Nearly all investors will want some combination (on a percentage basis) of these three major asset categories.
This slide establishes two important visuals for the audience:
Buckets help to segregate and simplify specific investment categories that will serve certain needs and objectives throughout an investment plan’s lifecycle.
The arrows will delineate movement or rebalancing of funds depending upon the advisor’s recommendation.
Once you have figured out your risk tolerance, investors/advisors will have a map to “filling your buckets”. For instance, Advisor A may recommend income from bucket two in order to fill bucket three. Advisor B may take that same income from bucket two and move to bucket one. Note the double sided arrows representing a potential movement between financial buckets/categories.
In addition to the three buckets, presenters should determine how much each bucket should appear to be “filled”, giving them the freedom to emphasize individual buckets more than others.
