dabigatran

Report
Role of novel oral anticoagulants
in ablation of atrial fibrillation
Mattias Duytschaever, MD,PhD
St Jan Hospital, Bruges
EHRA Training Centre for Electrophysiology
University Hospital Ghent
Brugada Syndrome 1992-2012
Twenty Years of Scientific Progress
Brussels 5th of Sept 2013
Catheter ablation of AF
38y old, paroxysmal AF and PSVT
Catheter ablation of AF
Cornerstone: A strategy of PV isolation and re-isolation
Segmental PVI
Circumferential PVI
Repeat PVI
Single Shot PVI
Robotic PVI
Catheter ablation of AF: Stroke/TIA
Incidence of peri-operative clinical stroke/TIA is 1%
Worldwide Survey
Updated Worldwide
Survey
1995-2002
Circ 2005
8745
2003-2006
Circ Arr 2010
16309
5.9
4.5
Stroke/TIA
0.94
0.94
Tamponade
1.22
1.31
Major Vascular
0.94
1.47
PV stenosis – intervened
0.74
0.29
Permanent phrenic nerve palsy
0.11
0.17
-
0.04
0.05
0.15
Date of procedures
Published
No of patients
Major Complications (%)
Atrium-esophageal Fistulae
Death
Catheter ablation of AF: Stroke/TIA
Incidence of peri-operative silent cerebral lesions
Diffusion weighted
Imaging (MRI)
ACE
(asymptomatic
cerebral emboli)
ACI
(acute cerebral
ischemia)
SCL
(silent cerebral
lesions)
ASE
(acute silent
emboli),…
air, gas, tissue, fat,
blood,…
BIBE 11-294E 08/2011
5
Catheter ablation of AF: Stroke/TIA
Incidence of peri-operative silent cerebral lesions
PVAC
Silent Cerebral Lesions (% of patients)
Irrigated-RF
50
40
30
Cryoballoon
38.9
37.5
1 to 5
lesions/
patient
1 to 5
lesions/
patient
20
8.3
10
5.6
Gaita et al (1)
7.4
4.3
Siklody et al (2)
Gaita et al, JCE 2011;22:961-968
No overt neurological events
6
BIBE
11-294E
Siklody
et al,
JACC08/2011
2011;58:681-688
Catheter ablation of AF: Stroke/TIA
How concerned should we be?
 SCL are observed up to 47% after cardiac valve replacement
Knipp et al, EJCTS 2004
 SCL are observed up to 14% after irrigated-tip RF ablation
Gaita et al, Circ 2010
 No proven relation between SCL and stroke/congnitive
dysfunction
Kruis et al, SCVA 2010
 Most SCL (up to 94%-100%) are transient
Deneke et al, Heart Rhythm 2011
Rillig et al, Circ A&E 2011
Gaita et al, Circ 2010
Catheter ablation of AF: Stroke/TIA
Aetiology of clinical stroke/TIA (1%)
Heart Rhythm. 2007
Jun;4(6):816-61.
Pre existing LA thrombus
Iatrogenic embolus
• Tissue: Thrombus at RF lesion
• Catheter: Char on RF catheter
• Sheath: Air or thrombus from sheaths
Catheter ablation of AF: Stroke/TIA
Risk factors for peri-operative stroke/TIA
Packer at al (JACC 2013)
Cryothermal
Lesion
Multi-centre
Cryoballoon
2.2 % stroke
Irrigated RF
Lesion
Wilber et al (JAMA 2010)
Multi-centre
Irrigated RF
0,0% stroke
Khairy et al. Circulation 2003
Catheter ablation of AF: Stroke/TIA
Risk factors for peri-operative stroke/TIA
• 39 strokes
in 6454
pts (0.6%)
• CHADS2
2 or more:
≈ 5-fold
risk
Di Biase et al, Circulation. 2010;121:2550-2556
How to avoid peri-operative stroke/TIA?
Strategies
•
•
•
•
•
•
•
•
•
•
•
Patient selection
Strict peri and intra operative anti-coagulation
Routine screening TEE?
Meticulous de airing of sheaths
Early heparinization before transseptal puncture
Continuous flush with heparinzed saline
Irrigated catheters, cryoballoon, …
Minimal catheter time in LA
Inspection of catheter if low power
Delay electrical ardioversion?
Avoid extensive substrate ablation (non-compliance)?
Patient selection
Safety
(%)
100.0
“Efficacy and safety go hand in hand”
99.0
CHADS 1-2
98.0
Man
Preserved
EF%
97.0
<65yrs
96.0
95.0
CHADS 0
Low
EF%
CHADS ≥3
Female
94.0
Chao et al HR 2011
65-74yrs
Chen et al JACC 2004
93.0
Zado et al, JCE 2008
92.0
91.0
90.0
40.0
≥75yrs
50.0
60.0
70.0
80.0
90.0
Efficacy
100.0
(%)
Duytschaever et al, Indian Pacing and Electrophysiology Journal, 2012
Strict peri and intra operative anti-coagulation
2012 HRS/EHRA/ECAS Expert Consensus Statement on Catheter and
Surgical Ablation of Atrial Fibrillation
• Pre-procedural anticoagulation: The Consensus Statement does not
specifically allude to this issue. The authors state however that the
anticoagulation guidelines that pertain to cardioversion should be adhered to in
patients presenting in AF.1
• Procedural anticoagulation: Heparin should be administered prior to or
immediately following transseptal puncture during AF ablation procedures and
adjusted to maintain an ACT of 300 to 400 seconds.
• Post-procedural anticoagulation: the Consensus Statement reemphasizes the
role of post-procedural warfarin (for at least 2 months) in all patients
regardless of CHADS.
• Real-life experience:
“warfarin for a least 1 month before and after the procedure, with or
without pre-operative bridging, in all patients”
Calkins et al, Heart Rhythm. 2012 ;9:632-696
Strict peri and intra operative anti-coagulation
A simplified strategy in CHADS 0 or 1 patients with par/pers AF taking
ASA (or no AC) at the time of procedural planning (n=214)
ASA
Month-1
H
Day -10
Day-1
•Stop ASA 11 days before the
procedure
•10 days of subcutaneous
LMWH
•Last injection evening before
procedure
Day 0
H
Day +1
• Heparin
before
transsept
•ACT>350s
• No TOE
• Protamine
ASA
Day +10
+1month
•24h of heparin
•10 days of
subcutaneous LMWH
•Restart ASA at D11
Day 0
Ablation
Injection of
LMWH
H
Heparin
Duytschaever et al, Journal of Cardiovasc Electrophysiol. 2013;24:855-860
Strict peri and intra operative anti-coagulation
A simplified strategy in CHADS 0 or 1 patients with par/pers AF taking
ASA (or no AC) at the time of procedural planning
Duytschaever et al, Journal of Cardiovasc Electrophysiol. 2013;24:855-860
Strict peri and intra operative anti-coagulation
A simplified strategy in CHADS 0 or 1 patients with par/pers AF taking
ASA (or no AC) at the time of procedural planning (n=214)
Stroke/TIA
Tamponade
Major vasc access
(%)
(%)
(%)
2.0
2.0
2.0
1.5
1.5
1.5
1.0
1.0
1.0
0.5
0%
0.5
0%
1.4%
0.5
Duytschaever et al, Journal of Cardiovasc Electrophysiol. 2013;24:855-860
Strict peri and intra operative anti-coagulation
2012 HRS/EHRA/ECAS Expert Consensus Statement on Catheter and
Surgical Ablation of Atrial Fibrillation
• Pre-procedural anticoagulation: The Consensus Statement does not
specifically allude to this issue. The authors state however that the
anticoagulation guidelines that pertain to cardioversion should be adhered to in
patients presenting in AF.1
• Procedural anticoagulation: Heparin should be administered prior to or
immediately following transseptal puncture during AF ablation procedures and
adjusted to maintain an ACT of 300 to 400 seconds.
• Post-procedural anticoagulation: the Consensus Statement reemphasizes the
role of post-procedural warfarin (for at least 2 months) in all patients
regardless of CHADS.
• Real-life experience:
“warfarin for a least 1 month before and after the procedure, with or
without pre-operative bridging, in all patients”
Calkins et al, Heart Rhythm. 2012 ;9:632-696
Strict peri and intra operative anti-coagulation
In practice: warfarin before & after; bridging or uninterrupted
Warfarin with bridging
Uninterrupted warfarin
(all INR>2)
warfarin
stop 3 days before
uninterrupted
LMWH
bridging untill evening before
-
TEE
before procedure
no TEE
Heparin
during procedure
during procedure
Protamine
end/before sheath pulled out
end/before sheath pulled out
LMWH
evening of procedure
-
warfarin
evening of procedure
evening of procedure
Strict peri and intra operative anti-coagulation
Preference for uninterrupted warfarin (case-controlled analysis)
Warfarin with bridging
(irrigated RF)
Uninterrupted warfarin
(irrigated RF)
Di Biase et al, Circulation. 2010;121:2550-2556
Strict peri and intra operative anti-coagulation
Preference for uninterrupted warfarin (randomised-controlled trial)
The COMPARE trial
Multi-centre prospective open-label, single-blind RCT
n= 1584 pts with AF at risk for TE, undergoing AF ablation
1:1 RCT, uninterrupted warfarin (W) vs bridging with LMW heparin (B)
TE: 0.25% (W) vs. 3.7%, (B) (p<0.001)
Major bleeding: 0.38% (W) vs. 0.76%, (B) (N.S)
Di Biase et al, The COMPARE trial, LB session, HRS, Denver 2013
Strict peri and intra operative anti-coagulation
Practical application for uninterrupted Warfarin
WARF
Month-1
H
Day -10
• Warfarin (INR >2.0)
• Last dose evening before
the proecdure
Day-1
Day 0
WARF
Day +1
• Heparin
before
transsept
•ACT>350s
• No TOE
• Protamine
Day +10
+1month
•No heparin
• Restart warfarin
evening of the
procedure
Day 0
Ablation
Dosage of warfarin of
paticular interest
All issues with VitK antagonists
INR control is essential
H
Heparin
Strict peri and intra operative anti-coagulation
What about NOACs?
TF/VIIa
ORAL
X
IX
VIIIa
“Direct fXa”
Inhibitors
IXa
Va
Apixaban
Edoxaban
Rivaroxaban
Xa
AT III
II
“Direct
thrombin”
Inhibitors
Ximelagatran
Dabigatran
IIa thrombin
Fibrinogen
Fibrin
Adapted from Weitz & Bates, J Thromb Haemost 2005
BIBE 11-294E 08/2011
22
Strict peri and intra operative anti-coagulation
What about NOACs?
Dabigatran
Rivaroxaban
Apixaban
direct thrombin inhibitor
direct fXa inhibitor
direct fXa inhibitor
Prodrug
yes
no
no
Bio-availiblity (%)
6%
60-80%
50%
Time to peak C (h)
3h
3h
3h
12-17h
5-13h
9-14h
80% renal
33% renal
25% renal
no
yes
no
150 & 110mg bid
20 mg od
5 mg bid
Mechanism
Half-life (h)
Renal clearance (%)
Food effect
Common Dosage
Antidote
BIBE 11-294E 08/2011
23
Strict peri and intra operative anti-coagulation
Can we extropolate? And if so, what is the ideal “uninterrupted”scheme?
Dabi 110mg
Dabi 150mg
Katsnelson,BIBE
Circulation
24
11-294E 08/2011 2012
What is the efficacy (TE events) and
safety (incidence of bleeds) of perioperative use of NOACs in the setting
of catheter ablation of Afib?
S/E of Strategies of ‟uninterrupted” NOACs
Published strategies (dabigatran compared to warfarin)
Last dose 24h
[36h in between
dosages]
DABIGATRAN
H
Morady et al
DABIGATRAN
Wazni et al
Month-1
Day -10
Day-1
Day 0
Day +1
Day +10
+1month
Last dose 12h
Wazni et al
[24h in between
dosages]
DABIGATRAN
H
DABIGATRAN
Lakireddy et al
Nin et al
Month-1
Last dose 0h
[12h in between
dosages]
Day -10
Day-1
DABIGATRAN
Month-1
Day -10
Day 0
Day +1
H
Day-1
Day 0
Day +10
+1month
DABIGATRAN
Day +1
Day +10
Dosage of dabigatran
of paticular interest
Maddox et al
+1month
Skipped dosage of
dabigatran
*“Goal of these strategies: to minimise time spent with subtherapeutic anticoagulation without compromising bleeding risk”
S/E of Strategies of ‟uninterrupted” NOACs
Last dose 24h before the procedure (Michigan experience)
Single centre, retrospective observational, non-randomised case controlled
n= 191 pts undergoing AF ablation with peri procedural dabigatran
53% parox AF, CHADS 1.0±0.9
Control: n=572 uninterrupted warfarin (INR 2-3)
Pre: >30days of D 150mg BD, last dose: 24h before
Peri: UFH to target ACT of 300-350s (after TS)
TEE in all (was negative in all, although last dose 24h), no protamine
Post: 1st dose of Dabi 4 hours after vascular hemostasis (>3months) (no bridging)
TE events: 0% (D) vs. 0% (W), NS
Major bleeds: 2.1% (1% tamponade)(D) vs 2.1% (1% tamponade)(W), NS
All pts with tamponade had uneventful recovery
Kim and Morady et al, Heart Rhythm 2013;10:483-489
S/E of Strategies of ‟uninterrupted” NOACs
Last dose 24h before the procedure (Michigan experience)
Kim and Morady et al, Heart Rhythm 2013;10:483-489
S/E of Strategies of ‟uninterrupted” NOACs
Last dose 24h before the procedure (Michigan experience)
Kim and Morady et al, Heart Rhythm 2013;10:483-489
S/E of Strategies of ‟uninterrupted” NOACs
Last dose 24h before the procedure (Cleveland experience)
Single centre, retrospective observational, non-randomised case controlled
n= 344 pts undergoing AF ablation with peri procedural dabigatran
≈60% paroxysm AF, CHADS 0 40%, CHADS 1 40% CHADS 2 or more 20%
Control: n=344 matched uninterrupted warfarin (INR 2-3)
Pre: >30days of D 150mg BD, last dose: 24h to 12hbefore
Peri: UFH to target ACT of 350-450s (before TS) (with protamine)
TEE only if presenting in AF and low compliance to AC
Post: 1st dose of D immediately after hemostasis (i.e. at the end of the procedure in the
EP lab)
TE events: 0,3% (D) vs. 0,3% (W), NS
Major bleeds: 1.2% (D) (0.9% tamponade) vs 1.5% (W) (0.9% tamponade), NS
All tamponades had uneventful recovery after protamine/ pericardiocentesis
Wazni et al, Circ EP 2013;6:460-466
S/E of Strategies of ‟uninterrupted” NOACs
Last dose 24h before the procedure (Cleveland experience)
Wazni et al, Circ EP 2013;6:460-466
S/E of Strategies of ‟uninterrupted” NOACs
Last dose 24h before the procedure
When held for approximately 24 hours before the procedure
(with a restart early after vascular
hemostasis), dabigatran appears to be as safe and effective
as uninterrupted warfarin for periprocedural anticoagulation
in patients undergoing catheter ablation for AF
S/E of Strategies of ‟uninterrupted” NOACs
Published strategies (dabigatran compared to warfarin)
Last dose 24h
[36h in between
dosages]
DABIGATRAN
H
Morady et al
DABIGATRAN
Wazni et al
Month-1
Day -10
Day-1
Day 0
Day +1
Day +10
+1month
Last dose 12h
Wazni et al
[24h in between
dosages]
DABIGATRAN
H
DABIGATRAN
Lakireddy et al
Nin et al
Month-1
Last dose 0h
[12h in between
dosages]
Day -10
Day-1
DABIGATRAN
Month-1
Day -10
Day 0
Day +1
H
Day-1
Day 0
Day +10
+1month
DABIGATRAN
Day +1
Day +10
Dosage of dabigatran
of paticular interest
Maddox et al
+1month
Skipped dosage of
dabigatran
*“Goal of these strategies: to minimise time spent with subtherapeutic anticoagulation without compromising bleeding risk”
S/E of Strategies of ‟uninterrupted” NOACs
Last dose 12h before the procedure (8-centre study)
Multi-centre (n=8) “prospective” observational, non-randomised case
controlled
n= 145 pts undergoing AF ablation with peri procedural dabigatran
57% par AF, CHADS 0 or 1 = 78%
Control: 145 matched uninterrupted warfarin
Pre: >30days of well-dosed D, last dose: 12h before
Peri: UFH (starting before TSP) to ACT 300-400s (protamine N.R.)
Post: D within 3 hours after hemostasis…
TE events: 2.1% (3 strokes)(D) vs. 0%, (W) (NS)
Major bleeds: 6% (9 tamponades)(D) vs 1% (2 tamponades)(W) (p=0.019)
Lakkireddy et al, JACC 2012;59:1168-74
S/E of Strategies of ‟uninterrupted” NOACs
Last dose 12h before the procedure (8-centre study)
In patients undergoing AF ablation, warfarin is safer and more effective than
periprocedural dabigatran
Lakkireddy et al, JACC 2012;59:1168-74
S/E of Strategies of ‟uninterrupted” NOACs
Published strategies (dabigatran compared to warfarin)
Last dose 24h
[36h in between
dosages]
DABIGATRAN
H
Morady et al
DABIGATRAN
Wazni et al
Month-1
Day -10
Day-1
Day 0
Day +1
Day +10
+1month
Last dose 12h
Wazni et al
[24h in between
dosages]
DABIGATRAN
H
DABIGATRAN
Lakireddy et al
Nin et al
Month-1
Last dose 0h
[12h in between
dosages]
Day -10
Day-1
DABIGATRAN
Month-1
Day -10
Day 0
Day +1
H
Day-1
Day 0
Day +10
+1month
DABIGATRAN
Day +1
Day +10
Dosage of dabigatran
of paticular interest
Maddox et al
+1month
Skipped dosage of
dabigatran
*“Goal of these strategies: to minimise time spent with subtherapeutic anticoagulation without compromising bleeding risk”
S/E of Strategies of ‟uninterrupted” NOACs
Last dose 0h before the procedure (“true non-interrupted”)
Single centre, retrospective observational, non-randomised case controlled
n= 212 pts undergoing AF ablation with peri procedural dabigatran
≈60% parox AF, CHADS 0.9±0.9
Control group: n=251 uninterrupted warfarin (INR 2-3)
Pre: >30days of D 150mg BD, last dose: morning of the procedure (0h)
Peri: UFH to target ACT of >350-400s (before or after TS)
TEE in all before procedure, protamine to reverse
Post: 1st dose of Dabi evening of the procedure (for >3months) (no bridging)
TE events 0.4% (TIA) (D) vs. 0% (W) (NS)
Bleeding: 0.9% (D) vs 2.3% (W) (NS)
All bleedings could be managed conservatively (none receiving reversal agents)
Maddox et al, JCE 2013;24:861-865
S/E of Strategies of ‟uninterrupted” NOACs
Last dose 0h before the procedure (“true non-interrupted”)
“True uninterrupted dabigatran appears to be as safe and effective as uninterrupted
warfarin for periprocedural anticoagulation in patients undergoing ablation of AF”
Maddox et al, JCE 2013;24:861-865
S/E of Strategies of ‟uninterrupted” NOACs
Efficacy
In patients undergoing AF ablation with peri-procedural dabigatran,
compared to uninterrupted warfarin, the TE event rate is…
• 0%
• 0.3%
• 2.1%
• 0%
• 0.4%
(vs 0%, NS)
(Kim et al)
(vs 0.3%, NS)
(Wazni et al)
(vs 0%, NS)
(Lakkiredy et al)
(vs 2%, NS)
(Nin et al)
( vs 0%, NS)
(Maddox et al)
dabigatran as effective as warfarin
S/E of Strategies of ‟uninterrupted” NOACs
A meta-analysis of 15 studies on 1823 patients on dabigatran
dabigatran as effective as warfarin
Boveda et al, Heart 2013;July
S/E of Strategies of ‟uninterrupted” NOACs
Safety
In patients undergoing AF ablation with peri-procedural dabigatran,
compared to uninterrupted warfarin, the major bleed event rate is…
• 2.1%
• 1.2%
• 6%
•• 0.9%
(vs 2.1%, NS)
(Kim et al)
(vs 1.2%, NS)
(Wazni et al)
(vs 1%, p<.005)
(Lakkiredy et al)
(-)
(Nin et al)
( vs 2.3%, NS)
(Maddox et al)
dabigatran as safe as warfarin
S/E of Strategies of ‟uninterrupted” NOACs
A meta-analysis of 15 studies on 1823 patients on dabigatran
dabigatran as safe as warfarin
Boveda et al, Heart 2013;July
S/E of Strategies of ‟uninterrupted” NOACs
Preliminary and incomplete efficacy data on rivaroxaban
In patients undergoing AF ablation with peri-procedural rivaroxaban,
(not compared to warfarin) the TE event rate is…
Last dose 72h
Last dose 36h
Last dose 24h
Last dose 12h
Last dose 0h
•
•
•
•
•
0%
(-)
(San Diego)
n=54
1%
(-)
(San Francisco)
n=120
0%
( vs 0%, NS)
(Lakkireddy et al) n=157 vs 157
0%
(-)
(Munich)
n=170
0%
(-)
(Reddy et al)
n=54
Rivaroxaban seems effective (as uninterrupted warfarin)
S/E of Strategies of ‟uninterrupted” Riva
Preliminary and incomplete safety data on rivaroxaban
In patients undergoing AF ablation with peri-procedural rivaroxaban,
(not compared to warfarin), the major bleed rate is…
Last dose 72h
Last dose 36h
Last dose 24h
Last dose 12h
Last dose 0h
•
•
•
•
•
N.R. (-)
(San Diego)
n=54
N.R. (-)
(San Francisco)
n=120
1.9% ( vs 2.5%, NS)
(Lakkireddy et al) n=157 vs 157
0%
(-)
(Munich)
n=170
2%
(-)
(Reddy et al)
n=54
Rivaroxaban seems safe (as uninterrupted warfarin)
Role of novel oral anticoagulants
in ablation of atrial fibrillation
• In patients undergoing AF ablation, the overall peri-operative
incidence of stroke/TIA is 0.5 to 1% (≈CHADS score)
• Among a variety of preventive measures, strict peri and intra
operative anticoagulation is essential
• In AF patients with no indication for routine anticoagulation, a short
and simplified AC strategy with LMWH seems safe and effective
• Uninterrupted warfarin should be preferred over warfarin with
bridging (COMPARE trial)
• When held for approximately 24 to 0 hours before the procedure
(with a restart early after vascular hemostasis), dabigatran appears
to be as safe and effective as uninterrupted warfarin
• These results appear to apply for FXa inhibitors as well
Role of novel oral anticoagulants
in ablation of atrial fibrillation
However …before updating the guidelines (or changing your
routine), one shoud realize the limitations of the aforementioned
studies
•
All studies are underpowered (low event rate)
•
All case controlled (not randomised)
•
Applicable to specific patients
What if warfarin before?
What is ASA or no AC before?
How to avoid peri-operative stroke/TIA?
….
Stefansdottir et al, Stroke 2013;44:1020-1025
How to avoid peri-operative stroke/TIA?
AF has already a negative effect on the brain (independent of cerebral
infarcts)
Brain volume (% of total intracranial
volume)
71.0
70.6
70.2
69.8
69.4
69.0
68.6
No AF
Parx AF
Pers/perm AF
Stefansdottir et al, Stroke 2013;44:1020-1025
How to avoid peri-operative stroke/TIA?
AF has already a negative effect on the brain (independent of cerebral
infarcts)
Brain volume (% of total intracranial
volume)
71.0
70.6
70.2
69.8
69.4
69.0
68.6
No AF
Parx AF
Pers/perm AF
Stefansdottir et al, Stroke 2013;44:1020-1025
Are we there yet?
Considerations
• No data so far on the effect of different dosages
• Check your own possible confounding factors: protamine, UFH before TS?
Operator? TEE before leading to non-ablation? TEE during? Ablation
strategy? Energy? antFXa activity if it could be measured? AF at
presentation? Cardioversion? Time to and dose to therapueitc ACT is longer
inn D vs W? single groin vs double groin centres? French size?
• What if antidote is availbale fXa inhibitors
Are we there yet?
How to buidl up evidence? Wanted? Realistic?
Any true RCTs in large sample size(in conrast to case controll,
…in contarts to meta analyis cumlating all pts): is this feasible
Larger Sample size: thousands of subjects need to be recruited
to assess the frequency of rare complications like stroke/TIA
and bleeding
Control arm: uninterrupted warfarin?
Dedicated apixaban trial is undergoing
Are we there yet?
Change the respective guidlienes….
• With the limited data available, if a strategy of bridging and
restarting of anrticoagulation is chosen and appropriately
excecuted, NOACS seem to allow such
• On the othe rhand a too aggressively shortened periprocedural cessation of NOACs and/or no bridging may be
less safe when compared to unintterrupted warfarin both
concerning bleeding and carioembolic complications
Heidbuchel et al, EHJ 2013;34:2094-2106
Remaining Q: What if on Warfarin before?
Californian single-centre experience on dabigatran
Single-centre retrospective observational, non-controlled
n= 123 pts consistently started with D after AF ablation
54% prior ECV, CHADS 1.2+/-1.0…
Control: no control arm
Pre: 45% warfarin (with bridge to LMWH) , 27.6% dabi, 21.1% ASA, 5.7%
no, (if DABI than last dose 36h to 60h before)
Peri: UFH to target ACT 225, at the end enoxa 0.5mg/kg
Post:
° 2nd injection of enoxa 0.5mg/kg 12h later (bridging)
° 1st dabigatran at 22h postablation (start or restart)
TE: 0% (uncontrolled)- Bleeding: 0% (uncontrolled)
Winkle et al, JCE 2012;23:264-268
Remaining Q: What if on Warfarin before?
What if warfarin before? Californian single-centre experience on
dabigatran
Winkle et al, JCE 2012;23:264-268
Acute Anticoagulation (Pericardioversion)
Practical flowchart
CHADS + = CHADS2
score ≥1
CHA2DS2VASc score ≥ 2
<48 hours
CHADSHeparin/LMWH 6
Cardioversion
No OAC 8
>48 hours or unknown
CHADS+
Heparin till INR 5
CHADSINR- or TOE-guided 2
CHADS+
INR- or TOE-guided 1
Cardioversion
Cardioversion
Cardioversion
Long-term OAC 7
4 weeks of OAC 4
Long-term OAC 3
From 5.6% stroke (Bjerkelund et al 1969) to 0.5%
″Uninterrupted NOAC″
Published 2012 strategies (dabigatran) (in every respected journal)
DABIGATRAN
Lakireddy
et al
Month-1
Winkle et
al
Day -10
H
Day-1
ASA or Bridged W or
DABIGATRAN
Month-1
Kim et al
Day -10
Duytschaev
er et al
(Michigan+
Heparin)
Day -10
Day-1
Day -10
Day +1
Day-1
Day-1
Day +10
+1month
DABIGATRAN
Day 0
Day +1
H
DABIGATRAN
Month-1
Day 0
H
DABIGATRAN
Month-1
DABIGATRAN
Day +10
+1month
DABIGATRAN
Day 0
Day +1
H
H
H
Day 0
Day +1
Day +10
+1month
DABIGATRAN
Day +10
+1month
″Uninterrupted NOAC″
Dabiagtran in bruges
Pre: dabiagtran last dose vening before
Peri: Heparin
Post:
° Heparine untill next day 16h
° 1st dabigatran next day 20h
Bruges
Safety of Catheter Ablation for AF
A Comparison of Non Comparative Trials
Calkins et al; Circ Arrhythmia Electrophysiol. 2009;2:349-361
Risk factors for Stroke/TIA in AF Ablation
Role of Operator Experience and Patient Profile
Major complications were defined as the ones that were life
threatening, caused permanent harm, and required
intervention or prolonged hospitalization. Thirty-nine
(3.9%) major periprocedural complications were observed.
Dagres et al, JCE 2009
“Uninterrupted” NOAC peri-AF ablation
“Controlled” and non-cntrolled dabiagtarn only data in every respected
Lakireddy
journal
DABIGATRAN
H
DABIGATRAN
et al
Month-1
Nin et al
Day -10
Day -10
Day-1
Day -10
Day +1
Day 0
Day-1
Day 0
Day +1
Day 0
+1month
Day +10
+1month
DABIGATRAN
Day +1
H
Day-1
Day +10
DABIGATRAN
H
DABIGATRAN
Month-1
Day 0
H
ASA or Bridged W or
DABIGATRAN
Month-1
Kim et al
Day-1
DABIGATRAN
Month-1
Winkle et
al
Day -10
Day +10
+1month
DABIGATRAN
Day +1
Day +10
+1month
“Uninterrupted” NOAC peri-AF ablation
Published 2012 strategies (dabigatran) (in every respected journal)
Lakireddy
et al
DABIGATRAN
Month-1
Day -10
H
Day-1
Day 0
DABIGATRAN
Day +1
Day +10
+1month
Pushy
Nin et al
DABIGATRAN
Month-1
Winkle et
al
Day-1
ASA or Bridged W or
DABIGATRAN
Month-1
Kim et al
Day -10
H
Day -10
Day -10
Day +1
H
Day-1
DABIGATRAN
Month-1
Day 0
DABIGATRAN
Day 0
Day 0
+1month
DABIGATRAN
Day +1
H
Day-1
Day +10
Day +10
Ultrasfe
+1month
DABIGATRAN
Day +1
Day +10
Safe
+1month
“Uninterrupted” NOAC peri-AF ablation
Published 2012 strategies (dabigatran) (in every respected journal)
Lakireddy
et al
DABIGATRAN
Month-1
Day -10
H
Day-1
Day 0
DABIGATRAN
Day +1
Day +10
+1month
Pushy
Nin et al
DABIGATRAN
Month-1
Winkle et
al
Day-1
ASA or Bridged W or
DABIGATRAN
Month-1
Kim et al
Day -10
H
Day -10
Day -10
Day +1
H
Day-1
DABIGATRAN
Month-1
Day 0
DABIGATRAN
Day 0
Day 0
+1month
DABIGATRAN
Day +1
H
Day-1
Day +10
Day +10
Ultrasfe
+1month
DABIGATRAN
Day +1
Day +10
Safe
+1month
S/E of Strategies of ‟uninterrupted” NOACs
A Mess study/ Multicentre/ No Clear protocol
Multi centre, retrospective observational, non-randomised case controlled
n= 202 pts undergoing AF ablation with peri procedural dabigatran
≈55% paroxysm AF, CHADS 0 40%, CHADS 1 40% CHADS 2 or more 20%
Control: n=202 uninterrupted warfarin (INR 2-3)
Pre: a mess
Peri: UFH to target ACT of 350-450s (before TS) (with protamine)
TEE only if presenting in AF and low compliance to AC
Post: 1st dose of D 12+/-10h after procedure
TE events: 2/202% (D) vs. 0% (W) (NS)
Major bleeds: 5/202% (D) vs 3/202% (W) (NS)
Haines et al, JICE 2013;june
“Uninterrupted” NOAC peri-AF ablation
What if bleed?
• No reversal agnets needed I guess because slast dose 24h
• Look at case reportAC monitoring could become usefull

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