ESC Congress FA eBook 2016 - 11B

Table 1. Safety and Efficacy Preserved With Dose Reduction of
Edoxaban in ENGAGE-AF

Table 2. Consistent Efficacy and Safety of Edoxaban in Elderly
Patients in ENGAGE-AF
Age
(years)

Edoxaban
(60/30 mg)

Warfarin

Stroke/SSE

< 65
65-74
≥ 75

1.9
1.6
1.9

1.1
1.8
2.3

Ischemic stroke

< 65
65-74
≥ 75

0.9
1.3
1.5

.09
1.1
1.7

Major bleeding

< 65
65-74
≥ 75

1.5
2.5
4.0

1.8
3.3
4.8

ICH

< 65
65-74
≥ 75

0.3
0.4
0.5

0.3
0.9
1.2

Primary Outcome Event Rate (%/year)
Edoxaban
Dose reduction
No dose
reduction

Warfarin

Hazard Ratio
(95% CI)

1.79

2.21

0.81
(0.58-1.13)

1.00

1.29

0.78
(0.61-0.99)

3.05

4.85

0.63
(0.50-0.81)

2.66

3.02

0.88
(0.76-1.03)

Interaction
P-value

Pint = .85

Major Bleeding (%/Year)
Dose reduction
No dose
reduction

Pint = .02

group and 3.5% in the warfarin group (HR, 0.89; 95% CI,
0.70 to 1.13; P < .001 for noninferiority). Among patients
who met dose reduction criteria, the rate of recurrent
VTE was 4.2% for warfarin versus 3.0% for edoxaban
30 mg (HR, 0.73; 95% CI, 0.42 to 1.26).
The evidence base from ENGAGE AF-TIMI 48 has
been extended with numerous additional analyses that
provide further insight into the efficacy and safety of
edoxaban in a broad array of subgroups, according to
Robert P. Giugliano, MD, SM, Brigham and Women's
Hospital, Boston, Massachusetts, USA. Increasing age is
associated with a 2-4 fold increase in the risk of stroke/
SEE, ischemic stroke, major bleeding, and intracranial hemorrhage (ICH; Table 2).8 However, edoxaban
was more effective than warfarin in reducing ischemic
and bleeding events, and the protection from ICH was
numerically even greater in older patients. Dr Giugliano noted that edoxaban and apixaban are the safest
NOACs to use in patients aged ≥ 75 years, with lower
rates of bleeding than warfarin in elderly patients, in
contrast to higher rates of major bleeding with dabigatran and rivaroxaban versus warfarin in older patients.9
Patients with a prior stroke or transient ischemic
attack (TIA), comprising 28% of the ENGAGE AF-TIMI
48 population, are another high-risk group that benefited from edoxaban. Although this group has a nearly
2-fold higher risk of stroke than those without such a
history, they experienced a similar relative reduction
but greater absolute reduction in events with edoxaban
as compared with warfarin (Table 3).10 Edoxaban also
has been shown to be efficacious in women and men,
stated Dr Giugliano, with an enhanced safety advantage
over warfarin in women.
A detailed analysis of bleeding in ENGAGE AF-TIMI 48
has shown a link between a lower rate of bleeding and
reduction in mortality with edoxaban versus warfarin.11
Fatal bleeding was significantly reduced with edoxaban

ICH, intracranial hemorrhage; SEE, systemic embolic event.

(35 deaths vs 65 with warfarin; P = .003). Edoxaban also
was associated with fewer bleeds that contributed to
death (24 vs 36 with warfarin), thus resulting in a significant reduction in total bleeding events that was related
to death (59 vs 101 with warfarin; P = .001). The analysis
also revealed that patients who interrupt anticoagulation after a major bleeding event were at a 70% increased
risk of subsequent death, thus physicians should strive
to resume anticoagulant as soon as it is safe to do so following a bleed, noted Dr Giugliano.
Precision medicine calls for giving the right drug
at the right dose to the right patient at the right time.
NOACs have a favorable profile compared with VKAs. Yet,
there are differences between the NOACs. Selecting the
optimal agent requires consideration of the individual
characteristics of the patient and what is known about
the different drugs in different populations, stated
Dr Giugliano. Factors to consider are dosing flexibility, drug-drug interactions, and strength of data in important patient subgroups, along with patient-related
Table 3. Equivalent Protection With Edoxaban in Patients With
and Without Prior Stroke/TIA
Annualized Event Rate (%)
Edoxaban
Prior stroke/TIA
No prior stroke/
TIA

Warfarin

Hazard Ratio
(95% CI)

2.44

2.85

0.86
(0.67-109)

1.24

1.41

0.88
(0.72-1.08)

0.62

1.09

0.57
(0.36-0.92)

0.30

0.73

0.41
(0.27-0.61)

Interaction
P-value

.86

Annualized ICH Rate (%)
Prior stroke/TIA
No prior stroke/
TIA

ICH, intracranial hemorrhage; TIA, transient ischemic attack.

.28



Table of Contents for the Digital Edition of ESC Congress FA eBook 2016

Contents
ESC Congress FA eBook 2016 - Cover1
ESC Congress FA eBook 2016 - Cover2
ESC Congress FA eBook 2016 - i
ESC Congress FA eBook 2016 - ii
ESC Congress FA eBook 2016 - Contents
ESC Congress FA eBook 2016 - 2
ESC Congress FA eBook 2016 - 3
ESC Congress FA eBook 2016 - 4
ESC Congress FA eBook 2016 - 5
ESC Congress FA eBook 2016 - 6
ESC Congress FA eBook 2016 - 7
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ESC Congress FA eBook 2016 - 11
ESC Congress FA eBook 2016 - 11A
ESC Congress FA eBook 2016 - 11B
ESC Congress FA eBook 2016 - 11C
ESC Congress FA eBook 2016 - 11D
ESC Congress FA eBook 2016 - 12
ESC Congress FA eBook 2016 - 13
ESC Congress FA eBook 2016 - 14
ESC Congress FA eBook 2016 - 15
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ESC Congress FA eBook 2016 - Cover3
ESC Congress FA eBook 2016 - Cover4
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