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Managing the Left Atrial Appendage:Concepts & Controversies
Carlos A. Morillo, MD, FRCPC, FACC, FHRS, FESC
Professor Department of Cardiac Sciences
Section Chief Cardiology Division, Libin Cardiovascular
Institute, University of Calgary
Zone Head Cardiology, South Eastern Alberta
Alberta Health Services
Adjunct Professor of Medicine/Cardiology
McMaster University
Associate Scientist Arrhythmia & Global Health
Population Health Research Institute
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Conflicts of Interest
I implant LAAC Devices….
Research Grants: Bayer, Biosense Webster, Biotronik, Boston
Scientific, Medtronic, Pfizer, St. Jude Medical, Transoma, CIHR,
WHO-TDR, COLCIENCIAS, Juan Valdez Café de Colombia, Other
Undisclosed Colombian Pharmaceutical Companies!
Honorarium: Biosense Webster, Boston Scientific, BMS,
Biotronik, Daiichi-Sankyo, Medtronic, Pfizer, St. Jude Medical,
Sorin, Transoma, Astra Zeneca, Boeringher Ingelheim, Procaps,
Sanofi-Aventis, Merck, Servier.
Advisory Boards: Medtronic, Biosense Webster, Boston
Scientific, Biotronik, Transoma, Schering Plough, Boeringher
Ingelheim, Sanofi Aventis, Procaps, Biocaps, Servier
Steering Committees: Medtronic, BSCI, Daiichi Sankyo,
Biosense Webster, STOP-HARM, ASAP-TOO
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Overview
LAA & Stroke
NOAC Evidence
LAAC Evidence
Future Trials
Current Guidelines
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Left atrial appendage: cul-de-sac
predisposed to stasis-precipitated thrombi
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“The immobility of the auricular
walls makes them
defenceless against
thrombotic deposits, as a
horse should be against flies without his cutaneous muscles.”
Acta Medica Scanda 1948
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“Serial sections of the left atrial appendage were prepared [in AF-patients with
embolic stroke]…in every case mural thrombus, not obvious to the naked eye,
was found in the interstices of the trabeculae carneae.”C.M. Fisher. Can Med Assoc J 1953; 69: 257.
1913-2012 (b. Waterloo, Ontario)
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Atrial Fibrillation16% of brain infarcts
Left Atrial Thrombi12% of brain infarcts
(3/4ths of AF-associated stroke)
Cerebral Small Artery
Disease
Carotid Atherosclerosis
Other Heart Disease
Aortic Arch Plaque
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91% of stroke in AF is caused by blood clots that form in the left atrial appendage (LAA)1
1 Blackshear JL. Odell JA., Annals of Thoracic Surgery. 1996;61:755-759
Fibrillation causes blood to stagnate in the LAA
The stagnant blood becomes an ideal environment for a
thrombus or blood clot to form
The blood clot, or portion of it, dislodges from the LAA and
travels through arterial system
The embolism lodges itself in the blood vessels of the brain,
restricting blood flow and causing a stroke
Images on file at Boston Scientific Corporation
Thrombus in the LAA
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Cactus
Chicken wing
Di Biasi L et al JACC2012;60;531-38.
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LAA Anatomy
Di Biasi L et al JACC2012;60;531-38.
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Windsock
Cauliflower
Di Biasi L et al JACC2012;60;531-38.
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Windsock
Cauliflower
Di Biasi L et al JACC2012;60;531-38.
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Windsock
Cauliflower
Di Biasi L et al JACC2012;60;531-38.
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Windsock
Cauliflower
Di Biasi L et al JACC2012;60;531-38.
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Stroke or systemic emboli (primary outcome events) in 4
large randomized trials comparing DOACs with high-
quality warfarin anticoagulation
Data shown are for higher dosages of dabigatran (150mg twice daily) and edoxaban (60mg daily).
Ruff CT et al. Lancet 2013 (on-line Dec 4th)
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DOACs vs. warfarin phase III RCTs in atrial fib:
Intracerebral hemorrhage
P Value
Dabigatran 110 mg BID P < .001
Dabigatran 150 mg BID P < .001
Rivaroxaban 20 mg QD P = .024
Apixaban 5 mg BID P < .001
Edoxaban 60 mg QD P < 0.001
Edoxaban 30 mg QD P < 0.001
Warfarin betterDOAC betterConnolly SJ, et al. N Engl J Med. 2009;361:1139–1151.Patel MR, et al. N Engl J Med. 2011;365:883–891.Granger C, et al. N Eng J Med. 2011;365:981–992.Giugliano RP, et al. N Engl J Med 2013; online Nov 19
0.25 0.50 0.75 1.00 1.25
HR (95% CI)0.00
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Stroke Treatment Option: Direct Oral
Anticoagulants (DOACs)
This chart is not based on a head-to-head trial and is not intended to suggest
head-to-head comparisons of the separate trials or the therapies under study.
TreatmentStudy Drug Discontinuation
RateMajor Bleeding
(rate/year)
Rivaroxaban1 24% 3.6%
Apixaban2 25% 2.1%
Dabigatran3
(150 mg)21% 3.3%
Edoxaban4
(60 mg / 30 mg)33 % / 34% 2.8% / 1.6%
Warfarin1-4 17 – 28% 3.1 – 3.6%
1Connolly, S. NEJM 2009; 361:1139-1151 – 2 yrs follow-up (Corrected) 2Patel, M. NEJM 2011; 365:883-891 – 1.9 yrs follow-up, ITT 3Granger, C NEJM 2011; 365:981-992 – 1.8 yrs follow-up, 4Giugliano, R. NEJM 2013; 369(22): 2093-2104 – 2.8 yrs follow-up.
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Stroke Treatment Option: Direct Oral
Anticoagulants (DOACs)
This chart is not based on a head-to-head trial and is not intended to suggest
head-to-head comparisons of the separate trials or the therapies under study.
TreatmentStudy Drug Discontinuation
RateMajor Bleeding
(rate/year)
Rivaroxaban1 24% 3.6%
Apixaban2 25% 2.1%
Dabigatran3
(150 mg)21% 3.3%
Edoxaban4
(60 mg / 30 mg)33 % / 34% 2.8% / 1.6%
Warfarin1-4 17 – 28% 3.1 – 3.6%
1Connolly, S. NEJM 2009; 361:1139-1151 – 2 yrs follow-up (Corrected) 2Patel, M. NEJM 2011; 365:883-891 – 1.9 yrs follow-up, ITT 3Granger, C NEJM 2011; 365:981-992 – 1.8 yrs follow-up, 4Giugliano, R. NEJM 2013; 369(22): 2093-2104 – 2.8 yrs follow-up.
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V2016
Despi
te NOA
C Ado
ption
and A
bility t
o
Switch
NOAC
s, Adh
erence
to
Antico
agulati
on Re
mains
a Chal
lenge
Sourc
e: Marti
nez C,
et al.
Therap
y Pers
istence
in Ne
wly Di
agnose
d Non-
Valvu
lar Atr
ial Fib
rillation
Treat
ed wit
h Warfa
rin or N
OAC.
A Co
hort S
tudy. T
hromb
Haem
ost. 20
15 De
c 22;1
15(1):3
1-9. do
i: 10.1
160/TH
15-04-
0350.
~30% o
f NOA
C patie
nts sto
p taki
ng an
y drug
at 2 y
ears
There is an unmet need of stroke risk
reduction for patients with AF who are
seeking an alternative to long-term OACs
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Stroke Treatment Option: Direct Oral
Anticoagulants (DOACs)
This chart is not based on a head-to-head trial and is not intended to suggest
head-to-head comparisons of the separate trials or the therapies under study.
TreatmentStudy Drug Discontinuation
RateMajor Bleeding
(rate/year)
Rivaroxaban1 24% 3.6%
Apixaban2 25% 2.1%
Dabigatran3
(150 mg)21% 3.3%
Edoxaban4
(60 mg / 30 mg)33 % / 34% 2.8% / 1.6%
Warfarin1-4 17 – 28% 3.1 – 3.6%
1Connolly, S. NEJM 2009; 361:1139-1151 – 2 yrs follow-up (Corrected) 2Patel, M. NEJM 2011; 365:883-891 – 1.9 yrs follow-up, ITT 3Granger, C NEJM 2011; 365:981-992 – 1.8 yrs follow-up, 4Giugliano, R. NEJM 2013; 369(22): 2093-2104 – 2.8 yrs follow-up.
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V2016
Despi
te NOA
C Ado
ption
and A
bility t
o
Switch
NOAC
s, Adh
erence
to
Antico
agulati
on Re
mains
a Chal
lenge
Sourc
e: Marti
nez C,
et al.
Therap
y Pers
istence
in Ne
wly Di
agnose
d Non-
Valvu
lar Atr
ial Fib
rillation
Treat
ed wit
h Warfa
rin or N
OAC.
A Co
hort S
tudy. T
hromb
Haem
ost. 20
15 De
c 22;1
15(1):3
1-9. do
i: 10.1
160/TH
15-04-
0350.
~30% o
f NOA
C patie
nts sto
p taki
ng an
y drug
at 2 y
ears
There is an unmet need of stroke risk
reduction for patients with AF who are
seeking an alternative to long-term OACs
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AF Treatment Options
*BSC currently has no ablation catheters FDA-approved for the treatment of AF
AF
Ablation* PacingDrugs for
Rhythm/Rate Control
Embolic Management
Drugs (warfarin)
Interventions
Surgical Ligation
LAA ClipsEndovascular
LAA
AND/OR
Drugs (dabigatran, rivaroxaban,
apixaban)
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Left Atrial Occluding Devices
LAALA
• PLAATO
(terminated)
• Watchman
• Amplatzer
• LARIAT
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Left atrial appendage clot on echo:91% of stroke in AF is caused by blood clots formed in the LAA1
Clot
Images on file at Boston Scientific Corporation
1 Blackshear JL, Odell JA, Annals of Thoracic Surgery, 1996;61:755-759
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Invasive procedures can successfully close the LAA
• Surgical approaches to thromboembolic prophylaxis have been explored since the 1940s
• LAA closure or obliteration has most often been considered as an adjunct to other cardiac procedures such as mitral valvotomy or cardiac bypass surgery
• Studies on patients undergoing LAA closure have shown a trend toward reduction in embolic events
73%
23%
0%0%
20%
40%
60%
80%
• Surgical LAA closure prior to the closure rates of 10%-73%1
Excision Ligation w/ Sutures
Ligation w/ Staples
1 Dawson AG et al. Interact Cardiovasc Thorac Surg. 2010;10:306-11 2 Kanderian et al. JACC. 2008;52:924–9
Meth
od
of
Successfu
lLA
A C
losure
2
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Currently Reported RCTs
Study Trial Size (N) Trial Type and Comparator Length of Follow up
LAAOS I
Healey, 2005
77 Pilot RCT; Surgical LAA
occlusion vs. No LAA
occlusion (control group).
13 months
Nagpal, 2009 43 Pilot RCT; Surgical LAA
occlusion vs. No LAA
occlusion (control group).
9 days
PROTECT-AF
Reddy, 2013
707 Percutaneous LAA
occlusion vs. No LAA
occlusion (control group).
2.3 years
LAAOS II
Whitlock, 2013
51 Pilot RCT; Surgical LAA
occlusion vs. No LAA
occlusion (control group).
1 year
PREVAIL trial
Holmes, 2014
407 RCT; 2:1 fashion;
Percutaneous LAA
occlusion vs. No LAA
occlusion (control group).
18 months
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WATCHMAN LAA Closure Device in situ
Holmes et al, 2009
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WATCHMAN®: Device Implant Procedure
• Procedure is performed under either general anesthesia or conscious sedation with fluoroscopic and transesophageal echocardiography (TEE) guidance
• Access to the left atrium is gained via the femoral vein and transseptal puncture
• The procedure takes 35-60 minutes on average and patients are monitored in the hospital for at least 24 hours following the procedure
Transseptal puncture
Placement of WATCHMAN ® in LAA
Images on file at Boston Scientific Corporation
Caution: In the United States, WATCHMAN is an investigational device limited by Federal law and investigational use only. Not for sale in the US. Prior to use please review device indications, contraindications, warnings, precautions, adverse events, and operational instructions. Only available according to applicable local law. CE Mark received in 2005
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WATCHMAN®: Device endothelialization
Canine Model – 30 Day
Canine Model – 45 Day
Human Pathology - 9 Months Post-implant (Non-device related death)
Images on file at Boston Scientific Corporation. Results in animal models may not necessarily be indicative of clinical outcomes.
Caution: In the United States, WATCHMAN is an investigational device limited by Federal law and investigational use only. Not for sale in the US. Prior to use please review device indications, contraindications, warnings, precautions, adverse events, and operational instructions. Only available according to applicable local law. CE Mark received in 2005
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WATCHMAN™ Device Clinical Program
Significantly improved safety results2
Pilot Early feasibility with >6 years of follow-up
Enrolled up to 1500 patients at ~ 60 sites
CAP
Registry
CAP2
WATCHMAN primary efficacy, CV death, and all-
cause mortality superior to warfarin at 4 years1
Expected rate of stroke reduced by 77% in
patients contraindicated to warfarin3
Improved implant success; procedure safety
confirmed with new and experienced operators4
PROTECT-
AF
ASAP
PREVAIL
1 Reddy, VY et al. HRS 2013.. 2 Reddy, VY et al. Circulation. 2011;123:417-424; 3 Reddy, et al. JACC. 2013; In Press. 4 Holmes, DR Jr et al., CIT 2013SH-230506-AD June15
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DemographicsDevice Patients
CharacteristicPROTECT AF
N=463
CAP
N=566
PREVAIL
N=269P value
Age, years71.7 ± 8.8 (463)
(46.0, 95.0)
74.0 ± 8.3 (566)
(44.0, 94.0)
74.0 ± 7.4 (269)
(50.0, 94.0)<0.001
Gender (Male) 326/463 (70.4%) 371/566 (65.5%) 182/269 (67.7%) 0.252
CHADS2 Score
(Continuous)
2.2 ± 1.2
(1.0, 6.0)
2.5 ± 1.2
(1.0, 6.0)
2.6 ± 1.0
(1.0, 6.0)<0.001
CHADS2 Risk Factors
CHF 124/463 (26.8%) 108/566 (19.1%) 63/269 (23.4%)
Hypertension 415/463 (89.6%) 503/566 (88.9%) 238/269 (88.5%)
Age ≥ 75 190/463 (41.0%) 293/566 (51.8%) 140/269 (52.0%)
Diabetes 113/463 (24.4%) 141/566 (24.9%) 91/269 (33.8%)
Stroke/TIA 82/463 (17.7%) 172/566 (30.4%) 74/269 (27.5%)
Most notable differences:Age, Diabetes, and Prior Stroke/TIA
PREVAIL results from Holmes, DR Jr et al., CIT 2013PROTECT AF and CAP data from Reddy, VY et al. Circulation. 2011;123:417-424.
Caution: In the United States, WATCHMAN is an investigational device limited by Federal law and investigational use only. Not for sale in the US. Prior to use please review device indications, contraindications, warnings, precautions, adverse events, and operational instructions. Only available according to applicable local law. CE Mark received in 2005
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Meta-Analysis Shows Comparable Primary Efficacy Results to Warfarin
Source: Holmes DR, et al. Holmes, DR et al. JACC 2015; In Press. Combined data set of all PROTECT AF and PREVAIL WATCHMAN patients versus chronic warfarin patients
HR p-value
Efficacy 0.79 0.22
All stroke or SE 1.02 0.94
Ischemic stroke or SE 1.95 0.05
Hemorrhagic stroke 0.22 0.004
Ischemic stroke or SE >7 days 1.56 0.21
CV/unexplained death 0.48 0.006
All-cause death 0.73 0.07
Major bleed, all 1.00 0.98
Major bleeding, non procedure-related 0.51 0.002
0.01 0.1 1 10
Favors WATCHMAN Favors warfarin
Hazard Ratio (95% CI)
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Meta-
Analy
sis Sh
ows C
ompa
rable
Prima
ry Eff
icacy
Resu
lts to
Warf
arin
PROT
ECT A
F 4 Yr
s/PRE
VAIL
2 Yrs
Sourc
e: Ho
lmes, J
. D. R
., S. K
. Dosh
i, et a
l. JAC
C 201
5; 65
(24): 2
614-2
623.
Comb
ined d
ata se
t of a
ll PRO
TECT
AF an
d PRE
VAIL
WATC
HMAN
patien
ts vers
us chr
onic w
arfari
n patie
nts
HR
p-valu
e
Effica
cy
0.79
0.22
All str
oke or
SE
1.02
0.94
Ische
mic str
oke or
SE
1.95
0.05
Hemo
rrhag
ic stro
ke
0.22
0.004
Ische
mic str
oke or
SE >7
days
1.56
0.21
CV/un
explain
ed de
ath
0.48
0.006
All-ca
use d
eath
0.73
0.07
Major
blee
d, all
1.0
0 0.9
8
Major
blee
ding,
non p
roced
ure-re
lated
0.5
1 0.0
02
0.01
0.11
10
Favo
rs WA
TCHM
AN
Fa
vors
warfa
rin
Hazar
d Rati
o (95
% CI)
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Device Reduced Ischemic Stroke Over No Therapy
* Imputation based on published rate with adjustment for CHA2DS2-VASc score (3.0); Olesen JB. Thromb Haemost (2011)
0
1
2
3
4
5
6
7
8
PROTECT AF PREVAIL
Only
CAP
Imputed
Ischemic Stroke
Rate*
Isc
he
mic
Str
ok
e R
isk
(Eve
nts
/10
0 P
ati
en
t-Y
ears
)
79%Relative
Reduction
67%Relative
Reduction
83%Relative
Reduction
Baseline
CHA2DS2-VASc = 3.4
Baseline
CHA2DS2-VASc = 3.8
Baseline
CHA2DS2-VASc = 3.9
FDA Oct 2014 Panel Sponsor Presentation. Hanzel G, et al. TCT 2014 (abstract)
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Long-term PROTECT AF Primary Efficacy(2621 Patient-years)
100
90
80
00 1 2 3 4 5
463 382 360 337 317 196
244 218 200 173 147 87
WATCHMAN
Control
Freedom
from
Primary
Efficacy
Event
(%)
Time (Years)
WATCHMAN
Control
HR: 0.61, 95% CI: 0.38 to 0.97;
p=0.0348
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Obse
rved R
ates o
f Majo
r Blee
ding O
ver
Time A
ccord
ing to
Trea
tmen
t Grou
p
LAAC
(n=73
2)
Long
-term
warf
arin
(n=38
2) Ra
te
Ratio
P value
Ble
eding
Rate
(n ev
ents
/ N at
risk)
Even
t Rate
per
100 p
t-yrs
(n ev
ents
/ N at
risk)
Bleed
ing Ra
te (n
even
ts/N a
t risk
)
Even
t Rate
per
100 p
t-yrs
(n
even
ts / N
at ris
k)
Overa
ll 10
.8
(79/73
2)
3.5
(79/22
68)
11.3
(43/38
2)
3.6
(43/11
87)
0.96
0.84
Post
Proc
edure
5.9
(40/68
2)
1.8
(40/22
55)
11.3
(43/38
1)
3.6
(43/11
80)
0.49
0.001
Desti
natio
n 3.2
(19/60
1)
1.0
(19/19
58
9.7
(35/36
0)
3.5
(35/10
04)
0.28
<0.00
1
Warfa
rin +
ASA
(81mg
)
daily
Clopid
ogrel
(75m
g) +
ASA (
325 m
g) da
ily
ASA (
325m
g) da
ily
Impla
nt 45
days
* 6 m
onths
Post
Proc
edure
Thera
py
Desti
natio
n The
rapy
*if lea
k >5m
m, pa
tients
rema
ined o
n warf
arin +
ASA u
ntil se
al do
cume
nted,
skipp
ing th
e clop
idogre
l + AS
A pha
rmac
othera
py
Price
, M. J
., V. Y
. Red
dy, e
t al. J
ACC:
CV In
terv 2
015;
8(15):
1925
-1932
Overa
ll peri
od de
fined
as af
ter ra
ndom
izatio
n to t
he en
d of fo
llow-up
; pos
t-proc
edura
l peri
od as
>7 da
ys aft
er ran
domi
zatio
n to t
he en
d of fo
llow-up
;
destin
ation
thera
py pe
riod a
s bey
ond 1
80 da
ys po
st-ran
domi
zatio
n, wh
en pa
tients
assig
ned t
o LAA
closu
re we
re elig
ible to
rece
ive as
pirin
alone
.
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Briceno D, et al. Circ EP 2015
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Network meta-analysis for stroke
• According to the random effects model, LAAC device was found to reduce the risk of stroke by 15% when compared with NOACS
www.HQOntario.ca
0.1 1 10
NOACS versus WARFARIN 0.88 (0.81 – 0.95)0.88 (0.44 – 1.87)
LAAC device versus NOACS 0.81 (0.48 – 1.41)0.85 (0.63 – 1.05)
LAAC device versus WARFARIN 0.71 (0.42 – 1.23)0.75 (0.38 – 1.44)
Treatment 1 vs. Treatment 2 O.R. (95% Cr.I.)
Favours Treatment 1 Favours Treatment 2
Fixed Effects Random Effects (Vague Prior)
Heterogeneity (Vague) = 0.1456 95% CrI (0.02675 – 0.6404)
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League table for the outcome of Stroke
LAAC device
0.85(0.63– 1.05)
NOACS
0.75(0.38 – 1.44)
0.88 (0.44 – 1.87)
WARFARIN
OR <1 Means the Treatment in Top Left is Better
www.HQOntario.ca
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Rankogram for the outcome of Stroke
0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1
1 2 3
Pro
babilit
y o
f Bein
g R
anked
Rank
Random Effects (Vague) Rankogram
LAAC device
NOACS
WARFARIN
Best Worse
www.HQOntario.ca
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All cause mortality
0.1 1 10
NOACS versus WARFARIN 0.89 (0.84 – 0.94)0.88 (0.80 – 0.97)
LAAC device versus NOACS 0.77 (0.52 – 1.17)
0.71 (0.49 – 1.22)
LAAC device versus WARFARIN 0.68 (0.46 – 1.02)
0.63 (0.44 – 1.08)
Treatment 1 vs. Treatment 2 O.R. (95% Cr.I.)
Favours Treatment 1 Favours Treatment 2
Fixed Effects Random Effects (Vague Prior)
Heterogeneity (Vague) = 0.03566 95% CrI (0.0006505 – 0.2938)
www.HQOntario.ca
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Hemorrhagic stroke
0.01 0.1 1 10
NOACS versus WARFARIN 0.45 (0.37 – 0.55)0.48 (0.10 – 2.30)
LAAC device versus NOACS 0.42 (0.11 – 1.35)0.45 (0.29 – 0.79)
LAAC device versus WARFARIN 0.19 (0.05 – 0.60)0.22 (0.05 – 0.94)
Treatment 1 vs. Treatment 2 O.R. (95% Cr.I.)
Favours Treatment 1 Favours Treatment 2
Fixed Effects Random Effects (Vague Prior)
Heterogeneity (Vague) = 0.2726 95% CrI (0.01987 – 1.246)
www.HQOntario.ca
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Ischemic stroke
www.HQOntario.ca
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GRADE Evidence Profile
www.HQOntario.ca
‡Downgraded for indirectness, precision
Comparison Direct evidence Indirect evidence
Network meta-analysis
LAAO closure device vs NOACS
OR[95% Cr.I]
Quality of evidence
OR[95% Cr.I]
Quality of evidence
OR[95% Cr.I]
Quality of evidence
Not available
Not applicable
0.83[0.43, 1.84]
ǂ
Low
Same as indirect evidence
Same as indirect evidence
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Case Presentation
• 76 yr old male Chronic AF since 2000
• Hypertension, Type II DM, Dyslipidemia, Stroke/TIA
• 2006 Left hemisphere (CT documented)
• July 2013 Right Hemispheric TIA (MRI)
• CKD Creatinine 520 eGRF =14.6, Dialysis 3/week
• Gastric Antral Vascular Ectasia Recurrent severe
bleeding with transfusions every 2 weeks.
• Chronic rheumatoid arthritis, Gout
• Polyclonal gamopathy M Spikes
• Factor XII Deficiency
• Referred to determine best Stroke Prevention Therapy!
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Stroke rate No OAC CKD
• eGRF 30-59 mL/min/1.73m2 =7.5%/yr
• eGRF < 30 mL/min/1.73m2 = 8.1%
• ESRD hemodialysis 2 – 10 greater incidence of stroke RR 6.1, 95% CI 5.1-7.1
• 10 – 33/1000 patient-yrs
• Hemorraghic stroke HR 6.83, 95% CI 5.87-7.92
Banerjee A, et al. Chest 2014;145:1370-82.
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Saw J, et al. J Cardiovasc Electrophysiol. 2017 Jan
27. doi: 10.1111/jce.13168. [Epub ahead of print]
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SS:888
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ESS: 400
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LAAOS III Project Office
Project Office: [email protected]
Co-Principal Investigators: Richard Whitlock and
Stuart Connolly
Research Coordinator: Kate Brady
2947 recruited to date
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J Am Coll Cardiol 2016;68:1929–40.
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J Am Coll Cardiol 2016;68:1929–40.
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