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1. Jeffrey I. Weitz, Jeffrey S. Healey, Allan C. Skanes and Atul Verma
Fibrillation Ablation
Periprocedural Management of New Oral Anticoagulants in Patients Undergoing Atrial
Print ISSN: 0009-7322. Online ISSN: 1524-4539
Copyright © 2014 American Heart Association, Inc. All rights reserved.
is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231Circulation
doi: 10.1161/CIRCULATIONAHA.113.005376
2014;129:1688-1694Circulation.
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2. 1688
Clinical Case
A68-year-old woman with
­well-controlled hypertension is
having 3 to 4 episodes of paroxysmal
atrial fibrillation (AF) each month.
Despite a ventricular rate of 80 to
100/min while in AF, she complains
of palpitations, chest discomfort, and
light-headedness. Oral flecainide failed
to improve her symptoms, and she
refuses to take amiodarone because
of concerns about its potential toxic-
ity. She was started on dabigatran (150
mg twice daily) for stroke prevention;
her creatinine clearance was calcu-
lated at 92 ml/min. AF ablation has
been scheduled, and advice is needed
regarding periprocedural dabigatran
management.
Introduction
AF, the most common cardiac arrhyth-
mia,isamajorcauseofstroke.1
Although
many AF patients are asymptomatic
or have adequate symptom palliation
with rate-controlling medications, some
require treatment strategies aimed at
maintaining sinus rhythm. In the United
States, it is estimated that >150 000 AF
patients undergo catheter ablation each
year in an attempt to achieve rhythm
control.2
Originally targeted to younger
AF patients without structural heart dis-
ease, catheter ablation is performed in a
broader population now that outcomes
have improved. Consequently, the num-
ber of ablation procedures performed is
expected to increase exponentially over
the next decade.
Current guidelines recommend anti-
coagulant prophylaxis in all but the
lowest risk AF patients. Until recently,
vitamin K antagonists, such as war-
farin, were the only option for stroke
prevention in such patients. This situ-
ation changed with the introduction
of new oral anticoagulants (NOACs),
which target thrombin or factor Xa.
With a more predictable anticoagulant
response and shorter half-lives than
warfarin, NOACs have the potential
to streamline periprocedural manage-
ment in AF patients undergoing abla-
tion. However, data with NOACs in
this setting are limited, and at times
contradictory, which complicates their
integration into routine practice in
patients undergoing catheter ablation.
Comparison of the
Pharmacological Properties
of the NOACs With Those of
Warfarin
NOACs have pharmacological proper-
ties that distinguish them from warfa-
rin. These are summarized in Table 1.
Need for Anticoagulation in AF
Patients Undergoing Catheter
Ablation
Stroke is one of the most feared com-
plications of catheter ablation.3
The
stimulus for thromboembolism, the
underlying cause of most strokes in
AF patients, differs before, during, and
after ablation, which may influence the
optimal choice of anticoagulant.
Anticoagulation Before AF Ablation
Because catheter manipulation dur-
ing ablation may dislodge preexisting
thrombi, it is important to minimize the
risk of left atrial thrombus formation
before the procedure. Guidelines rec-
ommend at least 4 weeks of therapeutic
anticoagulation before ablation in all
but the lowest-risk AF patients.4
With
their rapid and predictable anticoagu-
lant effects, therapeutic anticoagulation
(Circulation. 2014;129:1688-1694.)
© 2014 American Heart Association, Inc.
Circulation is available at http://circ.ahajournals.org DOI: 10.1161/CIRCULATIONAHA.113.005376
From the Departments of Medicine and Biochemistry, McMaster University, and Thrombosis andAtherosclerosis Research Institute, Hamilton, Ontario, Canada
(J.I.W.); the Department of Medicine, McMaster University, and Population Health Research Institute, Hamilton, Ontario, Canada (J.S.H.); the Department of
Medicine, Western University, London, Ontario, Canada (A.C.S.); and the Department of Medicine, University of Toronto, Toronto, Ontario, Canada (A.V.).
Correspondence to Jeffrey Weitz, MD, Thrombosis Atherosclerosis Research Institute, 237 Barton Street East, Hamilton, ON, L8L 2X2, Canada.
E-mail weitzj@taari.ca
Periprocedural Management of New Oral Anticoagulants
in Patients Undergoing Atrial Fibrillation Ablation
Jeffrey I. Weitz, MD; Jeffrey S. Healey, MD, MSc; Allan C. Skanes, MD; Atul Verma, MD
Clinician Update
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3. Weitz et al New Oral Anticoagulants and Ablation 1689
is more readily achieved with NOACs
than with warfarin. In addition, the
rapid offset of NOACs has the poten-
tial to obviate the need for bridging in
most patients.
Anticoagulation During AF Ablation
The risk of stroke increases during
AF ablation through mechanisms that
invoke all components of Virchow’s
triad. These include endothelial injury
induced by passage of sheaths and
catheters into the left atrium and by
application of ablation energy; hyper-
coagulability triggered by contact of
the blood with the foreign surface of
the ablation hardware and with throm-
bogenic debris generated at the abla-
tion interface; and altered blood flow
that occurs after conversion of AF to
sinus rhythm. These insults induce tis-
sue factor expression, which initiates
the extrinsic pathway of coagulation,
and DNA, RNA, and inorganic poly-
phosphates released from activated
or damaged cells trigger clotting
via the intrinsic pathway (Figure 1).
Consequently, the anticoagulant used
during the ablation procedure must
not only be capable of suppressing
clotting that occurs through the extrin-
sic tissue factor-initiated pathway,
but also that initiated via the intrin-
sic pathways. Multi-targeted antico-
agulants appear to do this better than
those that target only a single clot-
ting enzyme. For example, heparin is
better than fondaparinux at prevent-
ing catheter thrombosis in vitro,5
and
warfarin is superior to dabigatran for
stroke prevention in patients with
mechanical heart valves. However,
even the best anticoagulant strategy
may not eliminate stroke induced by
embolism of necrotic debris generated
at the ablation interface. Fortunately,
saline-irrigated ablation catheters have
reduced the risk of this complication.
Contemporary surveys report throm-
boembolic events, mainly presenting
as transient ischemic attacks, in ≈1%
of ablation patients.3
Anticoagulation After AF Ablation
There is a risk of stroke after ablation,
even in patients without preexisting
risk factors. This occurs because atrial
tissue remains stunned for several
weeks after the procedure, with a resul-
tant decrease in contractility. In addi-
tion, endothelium injured by ablation
energy requires time to heal, so that its
natural antithrombotic properties can
be restored. For these reasons, guide-
lines recommend continuing anticoag-
ulation for at least 2 to 3 months after
the procedure.4
Balancing Thromboembolic
and Bleeding Risks in Patients
Undergoing Catheter Ablation
The risk of stroke during catheter
ablation must be balanced with the
risk of bleeding during and after the
procedure. Access site bleeding is the
most common hemorrhagic complica-
tion because multiple vascular sites are
accessed with large sheaths during the
ablation procedure. Cardiac perforation
and subsequent tamponade as a conse-
quence of bleeding into the pericardium
is the leading cause of death in patients
undergoing ablation.3
Perforation can
occur during ­trans-septal access into
the left atrium, or as a result of the
application of ablation energy. In an
attempt to reduce the risk of tampon-
ade at the time of ­trans-septal puncture,
some centers use intracardiac echo-
cardiography to perform the puncture
under direct visualization. The need
to strike a balance between the risk of
stroke and the risk of serious bleeding
has prompted a variety of periproce-
dural anticoagulation strategies, which
span the spectrum from interrupted
therapy, with or without bridging, to
uninterrupted therapy.
Table 1. Comparative Pharmacology of Warfarin and the New Oral Anticoagulants
Characteristics Warfarin Dabigatran Rivaroxaban Apixaban
Target VKORC1 Thrombin Factor Xa Factor Xa
Prodrug No Yes No No
Bioavailability 100% 6% 60% to 80%* 60%
Dosing o.d. BID (o.d.) o.d. (BID) BID
Time to peak effect 4–5 d 1–2 h 2–3 h 1–2 h
Half-life 40 h 12–17 h 7–11 h 12 h
Renal clearance None 80% 33%† 25%
Monitoring Yes No No No
BID indicates twice-daily; o.d., once-daily; and VKORC1, C1 subunit of the vitamin K epoxide reductase
enzyme.
*Bioavailability of rivaroxaban decreases as the dose is increased because of poor drug solubility; with
once-daily doses of 20 and 10 mg, the bioavailabilities are 60 and 80%, respectively.
†Only 33% of rivaroxaban is excreted unchanged by the kidneys; an additional 33% is excreted as inactive
metabolites.
Figure 1. Stimuli for activation of
coagulation during AF ablation.
Guidewires and catheters activate factor
XII, thereby initiating the intrinsic pathway
of coagulation. DNA and RNA released
from cells damaged by ablation energy
and inorganic polyphosphates released
from activated platelets also activate
factor XII. Tissue factor (TF) exposed at
sites of endothelial injury or expressed by
monocytes in response to inflammatory
cytokines activates the extrinsic pathway
of coagulation. The intrinsic and extrinsic
pathways converge to activate factor X
and factor Xa, together with factor Va,
activates prothrombin (II) to thrombin (IIa),
which then converts fibrinogen (Fg) to
fibrin (Fn).
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4. 1690 Circulation April 22, 2014
Current Approaches to
Periprocedural Warfarin
Management
There is considerable experience with
warfarin in the AF ablation setting, and
periprocedural management has evolved
in many centers from an interrupted to
an uninterrupted approach (Figure 2 and
Table 2). Each is briefly discussed.
Interrupted Strategy
Typically, warfarin is withheld 5 days
before ablation. Many centers bridge
patients with intravenous heparin or
with subcutaneous low-molecular-
weight heparin (LMWH).6
Bridging is
often initiated 3 days before the pro-
cedure, because it takes at least 2 days
for the international normalized ratio to
fall below the therapeutic range when
warfarin is withheld. To minimize the
risk of bleeding during the procedure,
intravenous heparin is stopped 4 to 6
hours before ablation, whereas the last
dose of subcutaneous LMWH is usually
administered 12 hours before ablation.
To mitigate the thromboembolic risk
during ablation, intravenous heparin is
given immediately before or after trans-
septal puncture in bolus doses sufficient
to achieve an activated clotting time
(ACT) of 300 to 400 sec. This ACT tar-
get was chosen because it is associated
with a lower risk of thromboembolic
events thanACT values below these lev-
els.4
After completion of the procedure,
sheaths are removed when theACT falls
to 200 to 250 sec.4,6
To shorten the time
to sheath removal, some centers give
protamine sulfate to rapidly reverse the
anticoagulant effect of heparin.
Warfarin is restarted after ablation.
In many centers, LMWH bridging is
reinstituted several hours after sheath
removal and is continued until the
international normalized ratio is ≥2,
indicating a therapeutic level of anti-
coagulation with warfarin. The dose
of LMWH varies; some centers use
­full-dose regimens, whereas others use
half doses to reduce the risk of bleed-
ing.4,6
It is unclear whether preprocedure
bridging is necessary in patients at low
risk of thromboembolism, and accept-
able outcomes have been reported even
with low-dose LMWH bridging regi-
mens after the ablation. This is not sur-
prising because based on an annualized
risk of stroke of 1.5 to 2.8% in low-risk
patients, the attributable risk of stroke
with an interrupted strategy is probably
in the range of 0.004 to 0.008%.
Uninterrupted Therapy
Increasingly, AF ablation is being per-
formed with uninterrupted warfarin.6
The move to uninterrupted warfarin
was prompted by data suggesting that
heparin bridging around the time of
procedures increases the risk of bleed-
ing. Thus, in a randomized trial com-
paring interrupted warfarin and heparin
bridging with uninterrupted warfarin
in patients undergoing pacemaker or
cardioverter-defibrillator implantation,
the rate of device pocket hematoma
formation was 16% and 3.5% with
interrupted therapy and uninterrupted
warfarin, respectively.7
Even with unin-
terrupted warfarin, intravenous heparin
is given during the procedure in doses
sufficient to achieve theACT target out-
lined above, and sheaths are removed
when the ACT is near normal.4,6
Rates of thromboembolic and bleed-
ing complications with uninterrupted
warfarin have been compared with
those observed with interrupted therapy
and LMWH bridging. In retrospective
cohort studies from high-volume cen-
ters that include data on 6000 patients,
stroke or transient ischemic attack
occurred in 0.9% of 1348 patients in
the interrupted cohort and in none of
the 2618 patients receiving uninter-
rupted warfarin, even though the latter
group had higher CHADS2
scores and
a more persistent pattern of AF.8
Rates
of major bleeding in those receiving
interrupted and uninterrupted therapy
Figure 2. Graphical representation of periprocedural anticoagulation strategies in patients
undergoing ablation.
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5. Weitz et al New Oral Anticoagulants and Ablation 1691
were 0.8% and 0.4%, respectively, and
rates of pericardial effusion were 0.8%
and 0.5%, respectively. In patients
with complications, outcomes were no
worse with uninterrupted warfarin.
In a recent randomized study, inter-
rupted warfarin with LMWH bridg-
ing was compared with uninterrupted
warfarin in 1584 patients undergo-
ing AF ablation.9
The rate of major
bleeding was low and not signifi-
cantly different in the 2 groups (0.76
and 0.38%, respectively), but the rate
of minor bleeding was higher with
interrupted therapy than with uninter-
rupted warfarin (22 and 4.1%, respec-
tively; P0.001) as was the rate of
stroke (3.7% and 0.25%, respectively;
P0.001). Despite the small number of
events and the limitations of these stud-
ies, many high-volume centers have
embraced the uninterrupted warfarin
strategy because it streamlines care.
However, these are centers with suf-
ficient expertise to ensure low rates of
bleeding and perforation; it is unclear
whether similar results will be obtained
in lower volume centers.
Extrapolating From Warfarin
to NOACs
The strategies used for warfarin have
been extrapolated to NOACs and
include interrupted, minimally inter-
rupted, or uninterrupted approaches.
Interrupted Strategy
Dabigatran is often stopped for
extended periods of time before abla-
tion. In centers that have embraced
uninterrupted warfarin, patients are
sometimes switched from dabigatran
to warfarin at least a month before the
procedure; they undergo ablation with
uninterrupted warfarin and then are
switched back to dabigatran after the
procedure. To avoid switching from
a short-acting NOAC to long-acting
warfarin and back again, other cen-
ters withhold dabigatran for 5 days or
more before the procedure; the drug is
held for a protracted period to ensure
complete clearance by the time of abla-
tion. In some cases, LMWH bridg-
ing is provided as described above. A
similar approach is used with the other
NOACs, although there is less concern
about a prolonged half-life in patients
with renal impairment because, in con-
trast to dabigatran, rivaroxaban and
apixaban are only partially cleared
through the kidneys.
Minimally Interrupted or
Uninterrupted Therapy
Data from the Randomized Evaluation
of Long-term Anticoagulant Therapy
(RE-LY) trial provide some reassur-
ance about the safety of dabigatran in
the periprocedural setting. Thus, dur-
ing a mean follow-up of 2 years, 4500
patients enrolled in the trial under-
went 7500 procedures.10
Despite the
lack of an antidote for dabigatran, the
rate of major bleeding in patients who
underwent procedures within 24 hours
of study drug discontinuation was
significantly lower in those on dabi-
gatran than in those taking warfarin.
Furthermore, a higher proportion of
dabigatran-treated patients were able to
undergo their surgery or procedure 48
hours after study drug interruption,
likely reflecting the shorter ­half-life
of dabigatran relative to warfarin.10
Although these data are promising,
experience with dabigatran in patients
undergoing AF ablation is limited, and
consensus on optimal periprocedural
management has yet to be reached.
Nonetheless, there is mounting evi-
dence that a minimally interrupted
strategy is effective and safe with dabi-
gatran, and there is some evidence that
uninterrupted therapy may be possible
with rivaroxaban.
An early observational study that
included 290 patients undergoing AF
ablation in 8 high-volume centers
reported a higher rate of bleeding and
thrombotic complications in patients
on dabigatran than in those given
uninterrupted warfarin,11
but this was
a relatively small observational study
with inherent susceptibility to bias.
Furthermore, dabigatran was restarted 3
hours after sheath removal, which may
have contributed to the higher bleeding
rate. Recent studies have yielded more
encouraging results. For example, in
a study that randomized 90 patients
undergoing AF ablation to dabigatran,
which was stopped 24 hours before
the procedure, or to warfarin, the rate
of access site bleeding was reduced by
50% in those assigned to dabigatran.12
In another single-center cohort study
that included 763 consecutive patients
undergoing AF ablation, 191 patients
were receiving dabigatran.13
The drug
was held for 24 hours before the pro-
cedure, and was restarted 4 hours
Table 2. Anticoagulation Management Strategies Before, During, and After Ablation
Strategy Before Ablation During Ablation After Ablation
Interrupted
warfarin
Stop warfarin 5 days prior
to procedure and bridge
with LMWH; stop LMWH
12 h before ablation
Give heparin to
achieve an ACT
300 s
Stop heparin and consider protamine;
remove sheath when ACT is 250 s;
restart warfarin and bridge with
LMWH until INR is therapeutic;
re-evaluate at 3 mo
Uninterrupted
warfarin
Continue warfarin Give heparin to
achieve an ACT
300 s
Stop heparin and consider protamine;
remove sheath when ACT is
250 s; continue warfarin and
re-evaluate at 3 mo
Interrupted NOAC Stop NOAC 5 days or
more before procedure
and switch to warfarin or
bridge with LMWH
Give heparin to
achieve an ACT
300 s
Stop heparin and consider protamine;
remove sheath when ACT is
150 s; restart NOAC 6–8 h after
sheath removal; re-evaluate at 3 mo
Minimally
interrupted or
uninterrupted
NOAC
Stop NOAC 12–24 h
before procedure
Give heparin to
achieve an ACT
300 s
Stop heparin and consider protamine;
remove sheath when ACT is
250 s; resume NOAC 6–8 h after
sheath removal; re-evaluate at 3 mo
ACT indicates activated clotting time; INR, international normalized ratio; LWMH, low-molecular-weight
heparin; and NOAC, new oral anticoagulant.
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6. 1692 Circulation April 22, 2014
after sheath removal. Compared with
uninterrupted warfarin, there was no
increase in bleeding or vascular com-
plications with dabigatran. Another
single-center cohort study enrolled 999
consecutive patients undergoing abla-
tion; 376 patients were taking dabiga-
tran (150 mg twice-daily), whereas the
remainder were on warfarin and had a
therapeutic international normalized
ratio.14
Only 1 or 2 doses of dabigatran
were held before the ablation, and the
drug was restarted at the end of the
procedure; this strategy was compared
with uninterrupted warfarin. Using
propensity score matching to generate
a cohort of 344 patients in each group
with balanced baseline data, major
hemorrhage before the procedure
occurred in 1.1% and 1.6% of patients
in the dabigatran and warfarin groups,
respectively, and in 1.2% and 1.5% of
patients after the procedure. A single
thromboembolic event occurred in both
groups. Finally, in a study that included
720 consecutive patients undergoing
AF ablation in 3 ­high-volume centers,
298 received periprocedural dabi-
gatran, 153 underwent the procedure
with uninterrupted warfarin, and 269
had interrupted warfarin with LMWH
bridging.15
Dabigatran was held 12
hours before ablation and was restarted
in the evening after the procedure.
Rates of stroke or transient ischemic
attack in the 3 groups were 0.6, 1.3,
and 1.7%, respectively. Only in the
interrupted warfarin group was red cell
transfusion or an intervention required
to manage bleeding in 1.1% and 1.5%
of patients, respectively. Based on the
results of these studies, which are sum-
marized in Table 3, the risks of throm-
boembolic and bleeding complications
with minimally interrupted dabigatran
appear to be similar to those with unin-
terrupted warfarin; a conclusion sup-
ported by a recent meta-analysis.16
Although there is less information
about the efficacy and safety of other
NOACs in patients undergoing abla-
tion, data are emerging. Thus, in a
multicenter prospective study, uninter-
rupted rivaroxaban was compared with
uninterrupted warfarin in 157 patients
undergoing AF ablation.17
There were
no strokes, but 1 patient in each group
suffered a periprocedural transient isch-
emic attack; major bleeding occurred
in 1.9% of patients in the rivaroxaban
group and in 2.5% of those given warfa-
rin, a difference that was not statistically
significant. In another ­single-center ret-
rospective study, 170 patients underwent
ablation on uninterrupted rivaroxaban.18
There were no reported thromboembolic
complications or major bleeds. In a pro-
spective registry of patients undergoing
AF ablation in 8 centers, 321 underwent
the procedure with uninterrupted rivar-
oxaban and 321 had uninterrupted war-
farin. Rates of embolic complications
were 0.3% in both groups and rates of
major bleeding were 1.6% and 1.9%,
respectively.19
Based on these limited
data, it may be possible to perform AF
ablation with uninterrupted rivaroxa-
ban, but confirmation is needed.
Conclusions and
Future Directions
Balancing the risks of stroke and bleed-
ing remains a challenge in patients
undergoing AF ablation. For years,
interrupted warfarin with LMWH
bridging was the anticoagulation strat-
egy of choice based on the assump-
tions that (1) performing the procedure
on warfarin would increase the risk
of bleeding, and (2) bridging with
LMWH, a short-acting anticoagulant,
before and after the procedure would
reduce the risk of periprocedural stroke
without increasing the risk of bleeding.
Results of randomized clinical trials
suggest that both of these assump-
tions are wrong. Thus, uninterrupted
warfarin appears to be more effective
and safer than interrupted therapy with
LMWH or heparin bridging. It is likely
that switching patients back and forth
from long-acting anticoagulants like
warfarin to short-acting agents like
heparin or LMWH not only leaves
patients unprotected from thrombo-
embolic events for periods of time,
but also increases the risk of bleeding
because the two anticoagulants are
often overlapped.
Can the findings with warfarin be
translated to the NOACs? Although
the results of the studies to date sug-
gest that the answer is yes, there are
Table 3. Summary of Key Studies Comparing Dabigatran With Warfarin in Patients
Undergoing Ablation
Study Type
(Reference) n Dabigatran Regimen
Warfarin
Regimen Bleeding Rates
Thrombo-embolism
Rates
Multicenter
cohort (11)
290 Held morning of
procedure; restarted 4
h after procedure
Continuous 6% and 1% with
dabigatran and
warfarin, respectively
(P=0.019)
2.1% and 0% with
dabigatran and
warfarin, respectively
(P=0.25)
Single-center
randomized (12)
90 Held 2 doses before
procedure; restarted
when hemostasis
achieved
Continuous 20% and 44% with
dabigatran and
warfarin, respectively
(P=0.013)
0% and 2.2% with
dabigatran and
warfarin, respectively
(P=NS)
Single-center
cohort (13)
763 Held 2 doses before
procedure; restarted 4
h after procedure
Continuous 4.7% and 4.3%
with dabigatran and
warfarin, respectively
(P=0.8)
0% with dabigatran
and warfarin (P=NS)
Single-center
cohort (14)
999 Held 1 or 2 doses
before procedure;
restarted at procedure
end
Continuous 1.2% and 1.5%
with dabigatran and
warfarin, respectively
(P=0.74)
0.3% with dabigatran
and warfarin (P=NS)
Multicenter
cohort (15)
720 Held 1 dose before
procedure; restarted
evening after
procedure
Continuous
or interrupted
0%, 0.6%, and 5.6%
with dabigatran,
continuous warfarin,
and bridging,
respectively
(P=0.0001)
0.6%, 1.3%, and
0.7% with dabigatran,
continuous warfarin,
and bridging
respectively (P=0.76)
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7. Weitz et al New Oral Anticoagulants and Ablation 1693
questions that still need to be addressed.
For example, although a minimal
NOAC interruption strategy appears
to be effective and safe in patients
undergoing AF ablation, is the same
true with an uninterrupted strategy?
The answer to this question depends
on whether the risk of bleeding with
NOACs during the procedure is differ-
ent from that with warfarin. NOACs
are associated with less intracranial
bleeding than warfarin; is the same
true for intracardiac bleeding because
like the brain, the heart also is rich in
tissue factor? Even if the risk of bleed-
ing during ablation is similar or lower
than that with warfarin, what do we do
if tamponade occurs? The anticoagu-
lant effects of warfarin can rapidly be
reversed with a combination of vitamin
K and prothrombin complex concen-
trate. In contrast, there are no specific
antidotes for the NOACs. Although
prothrombin complex concentrate
reverses the anticoagulant effect of
rivaroxaban,20
we do not know whether
it attenuates bleeding. The disconnect
between reversal of the anticoagu-
lant activity of NOACs and control of
bleeding is highlighted by the observa-
tion that prothrombin complex concen-
trate administration does not influence
the prolonged activated partial throm-
boplastin time in dabigatran-treated
rabbits, yet it attenuates injury-induced
bleeding in a dose-dependent fashion.21
Antidotes for the NOACs are in
development. These include a neutral-
izing monoclonal antibody fragment
against dabigatran and a recombinant
variant of factor Xa that serves as a
decoy for oral factor Xa inhibitors,
such as rivaroxaban and apixaban.
Until such antidotes are available, a
minimal interruption strategy is likely
the safest approach for periprocedural
NOAC management in patients under-
going AF ablation.
Case Resolution
With a creatinine clearance 80 mL/
min, the half-life of dabigatran in the
described patient is ≈13 hours. Based
on the results of studies performed
to date, it would be reasonable to
recommend withholding 3 doses of
dabigatran so that the drug is stopped
24 hours before the procedure and is
held on the morning of the procedure.
During the procedure, heparin will be
given as described above. The patient
can be advised to resume dabigatran
therapy in the evening after the proce-
dure provided that at least 4 to 8 hours
have elapsed since sheath removal.
Bridging with LMWH is unnecessary
before the procedure because of the
low risk of stroke in the short period
that dabigatran therapy is withheld,
and is not required after the procedure
because of the rapid onset of action
of dabigatran. This strategy is being
prospectively evaluated in a large
cohort study that is being conducted
in Canada. In this study, dabigatran is
withheld for 24 hours before ablation
in patients with a creatinine clearance
50 mL/min and for 48 hours in those
with a creatinine clearance of 30 to 50
mL/min and resumption of dabigatran
is delayed for 8 hours after sheath
removal. In addition to cohort studies
like this, registries and randomized
trials are needed to define the optimal
periprocedural management of dabi-
gatran and other NOACs in patients
undergoing AF ablation.
Acknowledgments
Dr Weitz holds the Canada Research Chair
(Tier 1) in Thrombosis and the J.F. Mustard/
Heart and Stroke Foundation Chair in
Cardiovascular Research.
Sources of Funding
This work was supported in part by fund-
ing from Canadian Institutes for Health
Research and the Heart and Stroke
Foundation.
Disclosures
Dr Weitz has served as a consul-
tant and has received honoraria from
­Boehringer-Ingelheim, Bayer, Janssen
Pharmaceuticals, Bristol Myers Squibb, and
Pfizer. Dr Healey has received research fund-
ingfromBoehringer-Ingeheim,BristolMyers
Squibb, and Pfizer. Dr Skanes has received
honoraria from ­Boehringer-Ingelheim,
Bayer, and Pfizer; research funding from
Boehringer Ingelheim; and is on the
Physician Advisory Board for Biosense
Webster. Dr Verma has received research
funding from ­Boehringer-Ingelheim and
Bayer, and honoraria from Bayer.
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