modern management of atrial fibrillation, from blood pressure control ... · modern management of...
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Modern management of atrial fibrillation, from
blood pressure control to anticoagulation
Adel Khalifa S. Hamad, BMS, MD, FRCP(Canada)
Consultant Cardiologist & Interventional Cardiac Electrophysiologist
Bahrain Defence Force Hospital
Kingdom of Bahrain
December 6th, 2013
Pre
va
len
ce
, %
Age, Yr
Pre
va
len
ce
, %
Age, Yr
Prevalence of AF stratified by age
and gender
European age-related prevalence US age-related prevalence
(n=4053) (n=2590)
(n=7995) (n=10179)
Heeringa J et al. Eur Heart J 2006 Go AS et al, JAMA 2001
1. Dulli DA, et al. Neuroepidemiology 2003;22:118-123. 2. Lin HJ, et al. Stroke 1996;27:1760-1764.
AF-related strokes are associated with greater
disability and a higher mortality rate P
ati
en
ts w
ith
clin
ical
para
mete
r (%
) Disability at clinical presentation1
60
40
0
50
30
20
10
Severe limb weakness Bedridden
P<0.005 P<0.0005
Fata
l str
okes (
%)
30-day post-stroke mortality2
30
20
0
25
15
10
Strokes
with AF (N=103)
Strokes
without AF (N=398)
P<0.048
Strokes without AF (N=845) Strokes with AF (N=216)
Limitations of VKA therapy
Routine coagulation monitoring
Slow onset/ offset of action
Warfarin resistance
Numerous drug–drug interactions
Numerous food–drug interactions
Narrow therapeutic window (INR range 2.0–3.0)
Ansell J, et al. Chest 2008;133;160S-198S. Umer Ushman MH, et al. J Interv Card Electrophysiol 2008;22:129-137.
VKA therapy has several limitations
that make it difficult to use in practice
Frequent dose adjustments
Unpredictable response
INR control: Clinical trials VS. clinical
practice (TTR)
1. Kalra L, et al. BMJ 2000;320:1236-1239;
2. Samsa GP, et al. Arch Intern Med 2000;160:967-973.
Clinical trial1 Clinical practice2,3
<2.0 2.0–3.0 >3.0
Elig
ible
pati
en
ts r
ece
ivin
g W
arf
ari
n
(%)
38%
44%
18%
66%
9%
25%
INR
AK 14/41
Trials of new oral anticoagulants for
SPAF
Factor Xa inhibitors Direct thrombin
inhibitor
RE-LY
• Dabigatran
• ~18 000 pts
• PROBE design
• Mean CHADS2 2.1
• Stroke or systemic embolism
• Major bleeding
ROCKET-AF
• Rivaroxaban
• ~14 000 pts
• Double blind
• Mean CHADS2 3.5
• Stroke or systemic embolism
• Major and non-major clinically relevant bleeding
ARISTOTLE
• Apixaban
• ~18 000 pts
• Double blind
• Mean CHADS2 2.1
• Stroke or systemic embolism
• Major bleeding
AK 18/41
RE-LY® primary efficacy outcome: stroke or
systemic embolism
Dabigatran
110 mg BID
vs. warfarin
Dabigatran
150 mg BID
vs. warfarin
0.50 0.75 1.00 1.25 1.50
<0.001
<0.001
Superiority
P value
0.30
<0.001
Non-
inferiority
P value
Hazard ratio
Marg
in =
1.4
6
Connolly SJ et al. N Engl J Med 2009;361:1139–51; Connolly SJ et al. N Engl J Med 2010;363:1875–6
AK 20/41
ROCKET AF
primary efficacy endpoint ITT
Rivaroxaban
Warfarin
Cu
mu
lati
ve e
ven
t ra
te (
%)
0
1
2
3
4
5
6
Days since randomization
120 480 240 360 600 840 720 0
ITT population
HR=0.88 (0.75, 1.03) p<0.001 (non-inferiority)
p=0.12 (superiority)
Number of subjects at risk
Rivaroxaban 7,081 6,879 6,683 6,470 5,264 4,105 2,951 1,785
Warfarin 7,090 6,871 6,656 6,440 5,225 4,087 2,944 1,783
Stroke or systemic embolism
Patel MR et al. N Engl J Med 2011;365:883–891
AK 26/41
ARISTOTLE
Primary Efficacy Outcome
8726 8440 6051 3464 1754
8620 8301 5972 3405 1768
HR 0.79 (95% CI, 0.66, 0.95)
0 6 12 18 24 30
Months
4
3
2
1
0
Apixaban
Warfarin p (non-inferiority) <0.001
p (superiority) = 0.011
Perc
ent
with e
vent
Granger CB, et al. N Engl J Med. 2011;365:981-92.
21% RRR
Stroke or Systemic Embolism
AK 31/41
AK 1/41
LAA Occlusion procedures
Surgical Percutaneous
• PLAATO system
• WATCHMAN device
• Amplatzer cardiac plug
• LARIAT system
Events Total Rate Events Total Rate Rel. Risk Cohort (no.) pt-yr (95% CI) (no.) pt-yr (95% CI) (95% CI)
900 pt-yr 48 554.2 8.7 13 312.0 4.2 2.08 (6.4, 11.3) (2.2, 6.7) (1.18, 4.13)
0.8
0.9
1.0
0 365 730 1,095
PROTECT AF: Intent-to-Treat
Primary Safety Results E
ve
nt-
fre
e
pro
ba
bili
ty
Days
Device Control
ITT Cohort:
patients analyzed
based on their
randomly assigned
group (regardless of
treatment received)
244 143 51 11
463 261 87 19
WATCHMAN
Control
Randomization allocation (2 device : 1 control)
0.8
0.9
1.0
0 365 730 1,095
Eve
nt-
fre
e
pro
ba
bili
ty
Days
Events Total Rate Events Total Rate Rel. Risk Non- Cohort (no.) pt-yr (95% CI) (no.) pt-yr (95% CI) (95% CI) inferiority Superiority
900 pt-yr 20 582.3 3.4 16 318.0 5.0 0.68 0.998 0.837 (2.1, 5.2) (2.8, 7.6) (0.37, 1.41)
Device Control Posterior
Probabilities
Randomization allocation (2 device : 1 control)
ITT Cohort:
patients analyzed
based on their
randomly assigned
group (regardless of
treatment received)
244 147 52 12
463 270 92 22
WATCHMAN
Control
PROTECT AF: Intent-to-Treat
Primary Efficacy Results
AK 1/41
Mort
alit
y (
%)
Years
30
0 1 2 4
HR = 1.15 95% CI: 0.99–1.34
P = 0.08
3
Rhythm-control
Rate-control
0
25
20
15
10
5
5
AFFIRM: Mortality with rate and rhythm
control strategies
AFFIRM = Atrial Fibrillation Follow-up Investigation of Rhythm Management
Wyse DG et al. N Engl J Med 2002;347:1825–33
AFFIRM: Stroke incidence with rate and
rhythm control strategies
Wyse DG et al. N Engl J Med 2002
Inci
dence
(%
)
0
2
4
6
8
10
Ischaemic stroke
Intracerebral haemorrhage
Subdural/ subarachnoid haemorrhage
All CNS events
Rhythm-control
Rate-control
5.5
7.1
1.1 1.3 0.8
7.4
8.9
0.8
P = 0.79
P = 0.73
P = 0.68
P = 0.93
ATHENA study: Maintenance of sinus rhythm with
dronedarone delays hospitalization for CV causes or death
Hohnloser SH et al. N Engl J Med 2009
Hospitalization due to CV events or death from any cause
Cum
ula
tive inci
dence
, %
Years
60
n =
30
2327
2301
50
40
30
20
0 0 6 12 18 24
10
Placebo
Dronedarone
P<0.001
1858
1963
1625
1776
1072
1177
385
403
3
2
Technique of AF ablation
Ablation of triggering focus Circumferential PV isolation
MANTRA-PAF Medical Antiarrhythmic Treatment or Radiofrequency Ablation in
Paroxysmal Atrial Fibrillation
Cosedis Nielsen J et al, N Engl J Med 2012
MANTRA-PAF Medical Antiarrhythmic Treatment or Radiofrequency Ablation in
Paroxysmal Atrial Fibrillation
Quality of Life Scores
Cosedis Nielsen J et al, N Engl J Med 2012