Antithrombotic management in patients undergoing electrophysiological procedures: a European Heart Rhythm Association (EHRA) position document endorsed by the ESC Working Group Thrombosis, Heart Rhythm Society (HRS), and Asia Pacific Heart Rhythm Society (APHRS)
Antithrombotic management in patients undergoing electrophysiological procedures: a European Heart Rhythm Association (EHRA) position document endorsed by the ESC Working Group Thrombosis, Heart Rhythm Society (HRS), and Asia Pacific Heart Rhythm Society (APHRS)
Christian Sticherling (Chair 0 1
Switzerland) 0 1
Francisco 0 1
Gheorghe-Andrei Dan (Romania) 0 1
Michele Gulizia (Italy) 0 1
Sigrun Halvorsen 0 1
(Norway) 0 1
Gerhard Hindricks (Germany) 0 1
Karl-Heinz Kuck (Germany) 0 1
Angel Moya 0 1
Gregory Y.H. Lip 0 1
0 Document reviewers: Bulent Gorenek (Reviewer Coordinator;Turkey) , Julia H. Indik (USA), Paulus Kirchhof (UK), Chang-Shen Ma (China), Calambur Narasimhan (India), Jonathan Piccini (USA), Andrea Sarkozy (Belgium), Dipen Shah (Switzerland), and Irene Savelieva, on behalf of EP-Europace , UK
1 Marin , Co-chair; Spain
2 41 61 265 45 98. E-mail address:
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Since the advent of the non-vitamin K antagonist oral anticoagulant
(NOAC) agents, which act as direct thrombin inhibitors or
inhibitors of Factor Xa, clinicians are provided with valuable alternatives
to vitamin K antagonists (VKAs). At the same time,
electrophysiologists frequently perform more invasive procedures, increasingly
involving the left chambers of the heart. Thus, they are constantly
faced with the dilemma of balancing the risk for thromboembolic
events and bleeding complications. These changes in the rapidly
evolving field mandate an update of the European Heart Rhythm
Association (EHRA) 2008 consensus document on this topic.1 The
present document covers the antithrombotic management during
different ablation procedures, implantation or exchange of cardiac
implantable electronical devices (CIEDs), as well as the management
of peri-interventional bleeding complications.
The document is not a formal guideline and due to the lack of
prospective randomized controlled trials (RCTs) for many of the clinical
situations encountered, the recommendations are often ‘expert
opinion’. The document strives to be practical for which reason
we subdivided it in the three main topics: ablation procedure,
CIED implantation or generator change, and issues of
periinterventional bleeding complications on concurrent antiplatelet
therapy. For quick reference, every subchapter is followed by a
short section on consensus recommendations.
Many RCTs are ongoing in this field and it is hoped that this
document will help to prompt further well-designed studies.
Antithrombotic management in patients undergoing ablation procedures
Ablation of atrial fibrillation, left atrial arrhythmias and right sided atrial flutter
In patients with symptomatic paroxysmal or even persistent atrial
fibrillation (AF), catheter ablation is indicated when antiarrhythmic
drugs have failed in controlling recurrences or even as a first-line
therapy in selected patients.2 – 4
Patients with AF have an increased risk of thromboembolic
events, which varies according to the presence of several risk
factors.5,6 Apart from their intrinsic thromboembolic risks, ablation
in these patients increases thromboembolic risk due to the
introduction and manipulation of one or more catheters and long
sheaths into the left atrium, and also due to endocardial lesions
produced during ablation. Cerebral imaging studies have shown
embolic events post-ablation without clinical overt cognitive
The management of anticoagulation during ablation for the
prevention of thromboembolic events may, on the other hand,
increase the risk of bleeding complications during the procedure
The antithrombotic strategy in patients undergoing AF ablation
includes three different stages: pre-procedural treatment,
periprocedural anticoagulation, and post-procedural strategy.
Based on the 2012 Heart Rhythm Society/European Heart Rhythm
Association/ European Cardiac Arrhythmia Society (HRS/EHRA/
ECAS) consensus document of AF Ablation, the minimum criteria
concerning anticoagulation at the time of AF ablation are those
that apply to cardioversion of AF.2 All patients undergoing AF
ablation who present in AF for the procedure should be anticoagulated
for at least 3 weeks prior to AF ablation. If they have not been
anticoagulated prior to ablation, a transoesophageal echocardiography
(TEE) should be performed. In addition to adhering to these
wellestablished anticoagulation guidelines that apply to cardioversion,
the 2012 HRS/EHRA/ECAS consensus document recommends
that all patient being anticoagulated during AF ablation with heparin
to achieve an activated clotting time (ACT) of at least 300 s. This
writing group fully supports these prior minimum recommendations
Despite the lack of controlled trials, there is a general trend to
consider starting antithrombotic treatment before ablation,17 even
in patients who present for ablation in sinus rhythm. The higher the
patient’s stroke risk profile, the lower the threshold is to start
anticoagulation prior to ablation. This approach is in keeping with
current anticoagulation guidelines that apply to all AF patients.
The current guidelines recommend that the initial step is to
identify low-risk patients (CHA2DS2-VASc score ¼ 0 for males and 1
for females) who do not need any antithrombotic therapy (Step
1). Subsequent to this step, it is recommended that all patients
with a CHA2DS2-VASc score of ≥2 should be anticoagulated,
and that anticoagulation should also be considered for males
with a CHA2DS2-VASc score of 1 (Step 2).18 For those patients
treated with a VKA or a NOAC, the recommendation is to have
at least 3 weeks of effective stable international normalized ratio
(INR) at therapeutic levels (between 2 and 3 for VKA).19 – 23
Patients on a VKA should aim for an average therapeutic target range
(TTR) of .70% within the target INR of 2.0 – 3.0, to minimize the
risks of thromboembolism and bleeding.24,25 For those treated
with a NOAC, 3 weeks of anticoagulation is recommended in a
patient previously anticoagulation naive. Attention to drug
adherence and counselling of patients may help to emphasize the
importance of treatment.26
While effective oral anticoagulation is readily achieved when
starting a NOAC, the initiation of a VKA after pulmonary vein
isolation (PVI) requires bridging with a low-molecular-weight heparin
(LMWH) until therapeutic INRs are obtained. This is not an issue
if the ablation is performed on therapeutic INRs. Achievement of
an adequate TTR of .70% is dependent on many factors, and use
of the SAMe-TT2R2 score can aid decision-making on whether
patients are likely to do well on VKA with a high TTR (SAMe-TT2R2
score 0 – 2) or those patients where labile INRs are likely (with a
low TTR) and a NOAC may be a better therapeutic option
(SAMe-TT2R2 score .2).27
Several studies have compared the strategy of discontinuation of
VKA for 3 – 5 days before the ablation, with bridging therapy with
LMWH (until the evening before the procedure) with a strategy
consisting on performing ablation without interrupting VKA agents
with INR between 2 and 3.5. Of note, the available randomized data
does not compare bridging with unfractionated heparins.
RCT, randomized controlled trial; A4, atrial fibrillation ablation versus antiarrhythmic drugs; CACAF, catheter ablation for the cure of atrial fibrillation; MANTRA-PAF, medical
antiarrhythmic treatment or radiofrequency ablation in paroxysmal atrial fibrillation; RAAFT, radiofrequency ablation atrial fibrillation trial; STOP AF, sustained treatment of
paroxysmal atrial fibrillation; TIA, transient ischemic attack.
Several non-controlled studies have shown that performing
ablation with an uninterrupted VKA maintaining therapeutic INR levels
is not only safe but also decreases the rate of thromboembolic and
haemorrhagic complications.28 – 30 One recent controlled
multicentre study compared a strategy of discontinuing warfarin 2 – 3 days
before ablation with bridging therapy with LMWH with a strategy
consisting of performing ablation without interruption of warfarin.22
Patients with an INR of .3.5 were postponed and those with an
INR between 3 and 3.5 received fresh frozen plasma (which we
do not recommend) before the ablation. In this trial, patients in
whom the ablation was performed with therapeutic INR levels
had a lower rate of thromboembolic complications (0.25 vs. 4.9%,
P , 0.001) without significant differences in major bleeding
For patients treated with NOACs, these drugs should be started
at least 3 weeks before ablation, and treatment adherence
emphasized to the patient as there is no easy way to measure drug
One recent prospective randomized controlled trial compared
uninterrupted rivaroxaban to uninterrupted VKA and found similar
low rates of bleeding and thrombembolic events.32 Several
observational and non-controlled trials, have also analysed the role of
NOACs, specifically dabigatran and rivaroxaban, in patients
undergoing catheter ablation. The strategy of using NOACs in published
series is not homogenous: the last dose of dabigatran before
ablation varies depending on the different publications between 12
and 36 h, and some authors even performed the ablation without
interrupting dabigatran.33,34 For rivaroxaban, the last dose is usually
administered 24 – 36 h before the ablation.31,35 – 37 Data on the
safety about the use of NOACs in ablation have been contradictory,
but in general, thromboembolic and bleeding risks are probably
similar when comparing NOACs with an uninterrupted VKA
In patients receiving VKA agents, it seems reasonably not to
stop VKA administration and performing the ablation with INR
levels between 2.0 and 3.0 or even 3.5. For NOACs, RCTs are
ongoing, but it seems reasonable that, in patients treated with
dabigatran or rivaroxaban, ablation can be performed either by
stopping one or two doses before the ablation or even with
uninterrupted rivaroxaban.32,39,40 A TEE should be performed in
all patients in whom there is a doubt about the appropriate
anticoagulation in the 3 weeks before the intervention.2 Indeed, studies
have shown that 1.6 – 2.1% of patients who have been fully
anticoagulated undergoing PVI demonstrate a left atrial thrombus or
sludge.41 – 43 Some operators advise a TEE in all patients
undergoing AF ablation regardless of the presenting rhythm or stroke risk
Peri-procedural anticoagulant strategy
Regardless of the peri-procedural anticoagulant treatment, all
patients should receive full anticoagulation with intravenous heparin
A first loading dose of intravenous heparin of 5000 – 15 000 units
(or 90 – 200 U/kg) should be administered at the beginning of the
procedure. It has been shown that patients on VKA require lower
heparin doses than those on a NOAC.44 Some operators give this
first loading dose immediately after venous puncture just before
transseptal puncture (TSP),20,22,28,29,45 whereas others give a half
dose before and the remaining dose after completion of TSP,46
and the rest administer the loading dose immediately after
TSP.20,23,31,47 There are no controlled data comparing these
different strategies. In an European survey, which includes data from 78
centres in 20 different countries in Europe, 69% of the centres
administer the first loading dose after TSP, 18% before, and the
remaining 13% partly before and partly afterwards.17
All sheaths should be continuously flushed with heparinized
saline solution, with a suggested dose of 2000 units per
After the first loading dose of heparin, continuous heparin
infusion at an initial rate of 1000 – 1500 U/kg/h can be started depending
on the levels of ACT. Others tailor the administration to achieve the
target ACT by intermittently administering heparin between 2500
and 7500 U. The first ACT measurement should be performed
10 – 15 min after the loading dose and thereafter every 20 –
30 min. It must be borne in mind that the uninterrupted use of
VKAs or NOACs has an influence on the ACT and the time needed
to reach the target ACT.49 – 51 The optimal target ACT is .300 s,
which decreases the rate of thromboembolic events without an
increase in bleeding complications.30 At the end of the ablation,
it is recommended to remove the vascular sheaths when ACT
levels are at least ,250 s. Protamine may be administered for this
purpose.20,22,30,35,46 Accordingly, we recommend the
administration of a loading dose of 10 000 – 15 000 U of heparin before or
immediately after TSP followed by either continuous intravenous
heparin infusion or repeated heparin boli targeting ACT levels
Once the ablation has been finished and before initiating
anticoagulant treatment, it can be useful to perform transthoracic
echocardiography in order to rule out pericardial effusion or cardiac
tamponade. If intracardiac echocardiography (ICE) was employed,
it can be used at the and of the procedure to rule pericardial
In those patients in whom the procedure has been performed
with brief interruption of a NOAC, the next dose should be
administered after 3 – 4 h once haemostasis has been achieved. In those
patients who discontinued a VKA or had a low INR at the time of
ablation, LMWH should be administered at 4 – 6 h once haemostasis
has been achieved along with reinitiating VKA agents, maintaining
the administration of LMWH until therapeutic INR levels have
Oral anticoagulation should be continued for at least 2 months
after ablation, since there is evidence that the vast majority of
thromboembolic events occurs in the first 4 weeks after
ablation.52 Subsequently, the decision for oral anticoagulation depends
on the patient’s stroke risk profile and not on the perceived
success or failure of ablation. Currently, there are insufficient data
to support the concept that AF ablation reduces stroke risk post
The role of left atrial appendage occluder devices in the
periprocedural setting has not been studied, and is not recommended
pending new data.
Right-sided atrial flutter
The pre- and post-interventional anticoagulation management
described for patients undergoing PVI or ablation for left-sided atrial
flutter also applies for patients with right-sided, mostly
cavotricuspid-dependent, atrial flutter who present for ablation in
atrial flutter. The procedural risk for bleeding and
thromboembolism is lower, since the catheters remain in the venous circulation
only and there is no need for TSP or another access to the systemic
circulation. For this reason, it has become common practice to
perform catheter ablation of right-sided flutter in patients while on a
VKA with a therapeutic INR (INR: 2.0 – 3.0) and also in patients
who are taking a NOAC without interruption prior to ablation. In
patients who have not been anticoagulated before and present in
atrial flutter, a TEE should be done. After ablation of patients with
isolated atrial flutter and a CHA2DS2-VASc score of ≥2, an oral
anticoagulant (OAC) may be continued like in AF patients since
there is evidence of a very high incidence of subsequent AF in these
Antithrombotic management in patients undergoing atrial fibrillation catheter ablation for the maintenance of sinus rhythm: consensus recommendations
All patients undergoing AF catheter ablation who present for the
procedure in AF should be anticoagulated with a NOAC, or a VKA
with a therapeutic INR of 2.0– 3.0 for 3 weeks prior to the
procedure; or undergo a TEE to screen for thrombi prior to the
procedure; post procedure, patients should receive anticoagulation
for at least 2 months.
In patients receiving a VKA, the ablation should be performed without
interruption of VKA therapy.
During the ablation procedure, patients should receive unfractionated
heparin with an ACT of .300 s.
Transoesophageal electrocardiography can be useful before the
intervention to rule our left atrial thrombi in all patients with a
CHA2DS2-VASc score of ≥2.
In patients presenting in atrial flutter and undergoing right-sided atrial
flutter ablation of the cavotricuspid isthmus only, therapy with a
VKA and a NOAC should not be interrupted and continued for at
least 4 weeks after a successful ablation.
For patients with AF who present for ablation in sinus rhythm,
pre-procedural TEE or initiation of anticoagulation ≥3 weeks prior
to ablation can be useful, especially in those patients with a
CHA2DS2-VASc score of ≥2.
Transoesophageal electrocardiography can be useful in patients who
present for ablation in AF and who have been adequately
anticoagulated for 3 weeks or longer prior to ablation, especially in
those with a CHA2DS2-VASc score of ≥2.
In patients receiving a NOAC and with normal renal function, it is
reasonable to give the last dose 24 h before the ablation. For
patients on dabigatran and renal impairment, this period of
interruption is longer.
Uninterrupted NOAC therapy may be considered in some patients
For patients in sinus rhythm and a CHA2DS2-VASc score of 0 (males)
or 1 (females), it may be considered starting a NOAC on the day of
the procedure, post-ablation.
Transoesophageal electrocardiography may be considered in patients
who present for ablation in sinus rhythm and who have been
adequately anticoagulated for 3 weeks or longer prior to ablation,
especially in those with a CHA2DS2-VASc score of ≥2.
Ablation is not recommended in patients in whom no anticoagulation
can be administered during and after the procedure.
In patients on a VKA and an INR of .2 – 3, the VKA should not be
stopped and no bridging with a low molecular weight should be
Ablation of left-sided accessory pathways and focal left atrial tachycardia
Accessory pathways (APs) are located on the left side in more than
50% of cases and their ablation carries a higher acute success and a
lower recurrence rate than septal or right-sided accessory
Over the past years, the preferred access route for ablation
changed from the retrograde aortic access, targeting the ventricular
insertion site of the AP, to the antegrade transseptal approach
targeting the atrial insertion of the AP. In elderly patients, the
antegrade approach also avoids the crossing of potentially calcified aortic
valves and the associated embolic risk. Historical rates of cardiac
tamponade range from 0.13 to 1.1% and cerebrovascular accidents
from 0.15 to 0.49%.56,57
The access route is the same utilized for ablation of AF and
leftsided atrial tachycardia (AT). Although there are only limited data
concerning the real thromboembolic risk with contemporary
ablation equipment, it can be assumed that the actual risk is lower than
the rates reported from the 1990s and in the AF/AT population.
Patients undergoing AP ablation are also younger and have usually
no or few risk factors for thrombembolic events. Furthermore,
there is only a single catheter with or without one long sheath in
the left atrium or the left ventricle, and the ablation is usually focal
resulting in much shorter total ablation times and time spent in the
Since there is no scientific evidence supporting peri-interventional
anticoagulation, the potential risks of bleeding have to be taken into
account. Prior anticoagulant therapy is not warranted. After arterial
access, 5000 – 15 000 units (or 90– 200 U/kg) of intravenous sodium
heparin is recommended followed by 1000 U/h during the
procedure.1 Long sheaths should be continuously flushed to avoid thrombus
formation. There is no evidence, supporting the post-interventional
use of oral anticoagulation or aspirin.
Antithrombotic management in patients undergoing focal left atrial ablation of an accessory pathway or a focal atrial tachycardia: consensus recommendations
During the ablation procedure, it is recommended to give
unfractionated heparin with a target ACT of .300 s.
After focal left atrial ablation of an accessory pathway or an AT, oral
anticoagulation or the use of aspirin is not recommended unless
Ablation of right atrial arrhythmias (excluding atrial flutter)
The thromboembolic risk in patients undergoing right atrial ablation
is linked to venous access, the ablation procedure itself, and
comorbidities. The thrombotic risk is higher in the initial days after
The rate of systemic complications in published observational
studies on right atrial ablation procedures varies from 0 to 3.2%
(see Supplementary material online, Table S8). This includes
thromboembolic complications with an overall incidence of
0.6%.59 One study found a 5% incidence rate of asymptomatic
deep vein femoral thrombosis in patients who underwent
rightsided ablation.60 Risk factors were the use of large sheaths for a
prolonged duration. In one of the few randomized studies, comparing a
loading dose of 5000 UI heparin with no loading dose, only local in
situ thrombosis connected to the catheter was observed; the risk is
generally low, and risk factors include the number of the cannulation
sites and female gender, but not heparin use.59
Ablation of the right ATs (ATs, right accessory slow pathways,
and junctional tachycardias) is considered as low thrombotic risk
procedures.1 The management of right-sided atrial flutter differs
and is described above.
Antithrombotic management in patients undergoing right atrial ablation procedures (excluding atrial flutter): consensus recommendation
Unfractionated heparin should be considered during the procedure.
It is not recommended to start the patients on oral anticoagulation or
aspirin unless otherwise indicated.
Ablation of right-sided ventricular tachycardias
Reported complication rates for ablation of right-sided ventricular
tachycardia (VT) are ,1% in isolated right-sided procedures.61 – 65
In a single tertiary centre, Bohnen et al.66 reported a major
complication rate of 3.4%, although none of these patients was on oral
anticoagulation; also, there was no significant difference between
right-sided (3.2%) and left-sided (3.5%) idiopathic VT ablations.
Tokuda et al.67 investigated the cardiac perforation rate in 1152 VT
ablations of 892 patients between 1999 and 2010, and reported 11
cardiac perforations (1%), which occurred in right ventricular
(RV) or RV outflow tract mapping in 7 patients. As expected, the
RV seems to be more susceptible to perforation due to the thinner
wall than the LV.
Overall, right-sided procedures are at low risk for relevant
thromboembolic events. Heparin use seems not to be necessary
for right-sided procedures and deliver no clinical benefit, but might
be given in special situations (long-lasting procedure, history of
previous venous thromboemboli, and/or known risk factors for
thrombosis) or in the presence of right to left intracardiac shunts
that pose a risk of paradoxical emboli.68 Meticulous sheath
management with frequent flushing is required during the procedure,
and compression after pulling the sheath should be done with
care and only as long as necessary. Should patients require oral
anticoagulation or platelet inhibition for another reason, there is no
evidence mandating discontinuation of these agents before the RV
In patients on a VKA and a higher risk for thromboembolism, it is
safe to continue oral anticoagulation at an INR between 2 and
3.29,69,70 Studies addressing the NOACs in this context are not
available, but it seems reasonable to manage patients with stopping
the NOAC the evening before the day of intervention and
continue if no bleeding complications occurred 3 – 4 h after the
For planned epicardial access, an oral anticoagulation with a VKA
should be withdrawn to achieve an INR of ,1.5 and NOACs should
be discontinued for at least 48 h (longer for renal impairment, if
dabigatran is used). There is no proven benefit of administering
postinterventional aspirin or oral anticoagulation unless it is required for
Antithrombotic management in patients undergoing right ventricular catheter ablation: consensus recommendations
In patients with structural heart disease undergoing endocardial
ablation of a right ventricular tachycardia only, established therapy
with a VKA, a NOAC, or platelet inhibitors can be continued.
Unfractionated heparin should be considered during the procedure.
Before an epicardial ablation, it can be useful to stop NOACs 48 h
before the procedure.
Before an epicardial ablation, it may be considered to withhold VKA
until the INR is ,1.5.
Ablation of left-sided ventricular tachycardias
Therapeutic anticoagulation is paramount for the prevention of
potentially serious thrombotic complications in the treatment of
leftsided ventricular tachyarrhythmias (VT).1,2,68,72,73 Left-sided VT can
originate from the endocardium as well as epicardium, and left
ventricular (LV) access can be achieved via antegrade transseptal,
retrograde transaortic, or subxiphoid epicardial techniques. Specific
considerations are therefore needed depending on the access route.
Currently, no data comparing different anticoagulation methods
before, during, and after LV ablation exist (Table 2).
Pre-procedurally, there is most evidence for anticoagulation
management in patients with documented AF (see the section ‘Ablation
of atrial fibrillation and left atrial arrhythmias’), and current AF
anticoagulation guidelines should be followed due to the increased risk of
intra-procedural sustained ventricular arrhythmias and need for
cardioversion. Echocardiography to rule out LV thrombus is also
warranted in patients with reduced LV ejection fraction.
Although data in patients undergoing left-sided VT ablation are
lacking, there is consensus that, in patients on a VKA and a
therapeutic INR, OAC should not be interrupted for VT ablation. Should
an epicardial approach be likely, interruption of VKA 3 – 5 days prior
to the procedure with bridging therapeutic heparin or LMWH can
be considered. Pre-procedural anticoagulation is not required
unless otherwise indicated in patients without structural heart disease.
Open irrigation radiofrequency ablation is standard for the
treatment of left-sided VT and allows delivery of higher radiofrequency
current before the catheter tip temperature reaches the point of
coagulum formation.78 Although there are no current consensus
anticoagulation recommendations for left-sided VT ablation, due to the
thrombotic risk profile similarities with AF ablation, therapeutic
intravenous heparin is recommended in patients with and without
structural heart disease. When endocardial substrates are
suspected, full-dose heparin is generally given once transeptal access
is achieved. When epicardial access is needed, full-dose heparin
should only be given once this is achieved. If patients had already
received heparin, administration of protamine (1 mg per 100 units of
unfractionated heparin) before entering the epicardial space can be
useful. An initial bolus of 100 U/kg followed by intermittent boluses
or a continuous infusion of heparin to maintain an ACT of .300 s is
recommended. When only the epicardium is accessed, therapeutic
heparin is not required. All intravascular long sheaths should be
continuously flushed with heparinized saline to prevent clot
formation.72 The epicardial sheath should regularly be aspirated during
the procedure to reduce the risk of epicardial clot formation and
Post-procedure, aspirin 75 – 150 mg or oral anticoagulation for
1 – 3 months may be considered, although commonly used the
evidence for aspirin is weak and no antithrombotic therapy also is an
option. Anticoagulation is not required in patients without
structural heart disease or who have only received epicardial ablation
unless otherwise indicated. Epicardial sheaths should only be removed
once the ACT is ,300 s, and a pericardial drain is often left
intra-epicardially for up to 24 h until no further drainage occurs.
In patients with indications for anticoagulation or with structural
heart disease, a VKA or a NOAC can be started 4 – 6 h after
haemostasis is achieved following endo- and/or epicardial ablation, with
bridging heparin, LMWH, or a NOAC. For patients on VKA, bridging
with a NOAC will have an impact on the prothrombin time.79
As there are limited well-controlled studies on anticoagulation
management in left-sided VT ablation, the recommendations
represent expert consensus. Individual patient characteristics and
comorbidities should always be considered, and the thromboembolic
risk balanced with the risk of cardiac tamponade, bleeding, and
Antithrombotic management in patients undergoing ablation procedures for left ventricular tachycardia: consensus recommendations
It is recommended to give unfractionated heparin with a target ACT of
.300 s during the procedure.
It can be useful not to interrupt oral anticoagulation with a VKA before
ablation of a left VT.
It is recommended to stop oral anticoagulation with a NOAC at least
24 h before LV ablation (longer for dabigatran, if renal impairment is
A transthoracic echocardiography can be useful to rule out LV thrombi
before the ablation procedure.
When switching to an epicardial access during a LV ablation, it may be
considered to administer protamine before epicardial access.
After LV ablation, oral anticoagulation or aspirin for 4 – 12 weeks may
In the absence of another indication, oral anticoagulation before LV
ablation should not be given.
Antithrombotic management for the implantation of cardiac implantable electronic devices
Management of vitamin K antagonists
In the most recent worldwide survey (2009), there were an
estimated 1.25 million pacemaker and 410 000 implantable cardioverter
defibrillator operations.80 Between 14 and 35% of patients receiving
these devices require chronic OAC,81 – 84 and their peri-procedural
management may present a dilemma to physicians.85 This is
particularly true for the subset of patients with a moderate-to-high risk
(≥5% per year) of thromboembolic (TE) events.86 In patients
with non-valvular AF, this risk corresponds to a CHA2DS2-VASc
score of ≥3. Physicians responded to concerns about
periprocedural TE by treating moderate- to high-risk device surgery
patients with heparin bridging. Previous guidelines recommended
this as standard of care.87 However, it became clear that there is a
substantial risk of clinically significant device pocket haematoma
related to heparin bridging. Importantly, device pocket
haematomas can necessitate prolonged cessation of anticoagulation,
with the attendant risk of TE,88,89 they can significantly increase
the duration and cost of hospitalization;90 sometimes, reoperation
Finally and perhaps most importantly, there is an association
between haematoma formation and subsequent device system
infection. For example, in the REPLACE registry,91 patients with
infections were 20-fold more likely to have had postoperative
haematomas. Device system infections usually require complete
system removal, which has significant associated morbidity,
mortality, and cost to the healthcare system.
In response to these issues, some centres started performing
pacemaker and defibrillator surgery without interruption of
warfarin anticoagulation.92 – 95 Two small randomized trials were
inconclusive.96,97 In the first of these, 4 of 51 patients (7.8%) from the
bridging arm and 4 of 50 (8.0%) from the VKA arm developed
pocket haematoma following the implant. A third, much larger, large
clinical trial, BRUISE CONTROL (Bridge or Continue Warfarin for
Device Surgery Randomized Controlled Trial),98 patients (n ¼
681) with an annual risk of TE of 5% or greater were randomly
assigned to continued warfarin or heparin bridging (Table 3). The
primary outcome was clinically significant haematoma, which was
defined as prolonging hospitalization, necessitating interruption of
anticoagulation, or requiring reoperation. Clinically significant
haematoma occurred in 12 of 343 (3.5%) patients in the
continuedwarfarin arm and 54 of 338 (16.0%) patients in the heparin-bridging
arm [relative risk, 0.19; 95% confidence interval (CI) 0.10 – 0.36; P ,
0.001]. Major surgical and thromboembolic complications were rare
and not significantly different between arms. They included one
episode of cardiac tamponade and one myocardial infarction in the
heparin-bridging arm, and one stroke and one transient ischaemic
attack (TIA) in the continued-warfarin arm. It should be noted
that exceptions to operating without interruption of warfarin were
sub-pectoral implants and lead extraction.98
Importantly, BRUISE CONTROL did not include patients at a
lower embolic risk (,5% annual risk of TE).98 Current international
thrombosis guidelines suggest temporary discontinuation of
warfarin for these patients, without heparin bridging.87 However,
physicians may also consider continuing warfarin in these patients,
especially if there is any history of previous embolic stroke or
TIA (Figure 1). This strategy is corroborated by two recent
Device implantation in patients receiving vitamin K antagonists: consensus recommendation
In the following patient groups with AF, it is recommended to perform
device surgery without interruption of VKA.
(i) Patients with non-valvular AF and a CHA2DS2-VASc score
(ii) Patients with a CHA2DS2-VASc score of 2 due to stroke or TIA
within 3 months.
(iii) Patients with AF planned for cardioversion or defibrillation
testing at device implantation.
(iv) Patients with AF and rheumatic valvular heart disease.
In the following patient groups with prosthetic heart valves, it is
recommended to perform device surgery without interruption of
(i) Prosthetic mitral valve.
(ii) Caged ball or tilting disc aortic valve.
(iii) Bileaflet aortic valve prosthesis and AF and a CHA2DS2-VASc
score of ≥2.
In patients with severe thrombophilia, it is recommended to perform
device surgery without interruption of VKA.
In patients with recent venous thromboembolism (within 3 months), it
is recommended to perform device surgery without interruption of
The INR on the day of surgery should be under the upper limit of the
prescribed therapeutic range for the patient (usually ≤3; ≤3.5 for
some valve patients.
In patients with an annual risk of TE events ,5% either perform
surgery without interruption of VKA or interrupt VKA 3 – 4 days
before surgery, no heparin bridging is recommended.
Interruption of VKA and bridging with an unfractionated heparin or
LMWH should be avoided.
Management of non-vitamin K oral anticoagulants
Of the NOACs approved for use for prevention of stroke and
systemic embolism in patients with AF, data on general peri-operative
experience with dabigatran and rivaroxaban have been published;
the key points from these two studies are:101,102
) Temporary interruptions for procedures/surgery are common
(between 10 and 15% of patients per year).
) About 10% of temporary interruptions are for pacemaker or
) Even brief temporary interruptions, carefully controlled in the
environment of clinical trials, are associated with an
approximately three-fold increase in stroke/systemic embolism.
The results of BRUISE CONTROL cannot be applied to patients
on NOACs.98 Rowley et al.103 recently published the first report on
continuous anticoagulation with a NOAC during implantation of
cardiac rhythm devices. Dabigatran was administered uninterrupted
with no missed doses in 11 patients, and 1 patient developed a
pocket haematoma. Jennings et al.104 reported on 48 patients having
device surgery with uninterrupted dabigatran. Bleeding complications
occurred in 1 of 48 patients (2.1%; late pericardial effusion).
Whether it is better to operate without interrupting these new
agents or with temporary cessation is currently unclear, and more
data are required. One such clinical trial is ongoing (continued vs.
interrupted dabigatran at time of device surgery: BRUISE
CONTROL 2, Clinicaltrials.gov NCT# 01675076). Until additional data
are available, we recommend interruption of NOACs for device
surgery, without heparin bridging. The period of peri-operative
discontinuation should be based on the original NOAC clinical trials
and as detailed in the respective product monographs (see Table 4
for summary). This recommendation is consistent with the EHRA
Practical Guide on the use of NOACs in patients with non-valvular
There are no data to guide when to restart NOACs after device
surgery. In the major NOAC clinical trials, the NOACs were
restarted at the physician’s discretion when haemostasis was
satisfactory.101,102 Physicians are concerned that early resumption of a
NOAC, with their rapid onset of action, may have similar effects
on postoperative bridging, i.e. result in significant numbers of
haematomas. Hence, in patients, with an annual risk of TE .5%,
we suggest giving the first dose of NOAC 24 h after surgery. In
patients with a lower risk of TE (e.g. ,5%), it would seem reasonable
to wait for .48 h after surgery. More data are required to refine all
of these recommendations regarding NOAC management around
Device implantation in patients receiving non-vitamin K oral anticoagulants: consensus recommendations
Non-vitamin K oral anticoagulants should probably be temporarily
discontinued for all device surgery.
The period of discontinuation should be based on product
It is suggested that the first dose of NAOC should be ≥24 – 48 h after
surgery. The timing of the resumption should be based on individual
assessment of the competing risks of stroke risk and pocket
Management of antiplatelet drugs
There are no randomized trials regarding antiplatelet (AP)
management around device surgery. However, there are data from a
number of observational studies (Table 5) and a recent meta-analysis
(Figure 2).105 The meta-analysis found that the estimated odds of
Patients on vitamin K antagonist therapy undergoing a cardiac electronic device implantation
Estimate the annual risk of thromboembolic events
Atrial fibrillation/flutter Prosthetic heart valves:
Patients with non-valvular AF Prosthetic mitral valve
and a CHA2DS2-VASc score of ≥3 Caged ball or tilting disc aortic
Patients with AF planned for valve
cardioversion or defibrillation Bileaflet aortic valve prosthesis
testing at device implantation and AF and CHA2DS2-VASc score
Patients with AF rheumatic of ≥2
valvular heart disease
Recent VTE (within 3 months)
Perform device surgery without
interruption of VKA
Stop VKA 3–4 days before surgery
Perform surgery without
interruption of VKA
Check INR 3–7 days before the procedure (to allow dose adjustment)
Check INR on the day of procedure
The INR on the day of surgery should be ≤ the upper limit of the prescribed therapeutic range for the patient,
usually ≤3 (or ≤3.5 for some prosthetic heart valve patients)
bleeding were increased by 5.0 times (95% CI 3.0 – 8.3) for dual AP
therapy. There was a non-significant trend (OR 1.5; 95% CI 0.9 – 2.3)
for single AP therapy relative to the no therapy group.105 For the
392 patients on dual AP therapy included in this analysis, there
were no reports of acute ischaemic events or in-stent thrombosis.
For recommendations of the management of antiplatelet therapy
at the time of CIED implantation, refer the section ‘Concurrent
antiplatelet therapy’ later in this document.
Management of peri-interventional bleeding complications
The management of bleeding in patients while on antithrombotic
therapy is defined in relation to its severity as either major, clinically
relevant non-major or minor. The definition for major bleeding in
surgical patients was defined in 2010 by the International Society
of Thrombosis and Haemostasis, and comprises fatal bleeding,
bleeding that is symptomatic and occurs in a critical area or organ
(intracranial, intraspinal, intraocular, and retroperitoneal),
extrasurgical site bleeding causing a fall in haemoglobin level of 20 g/L,
surgical site bleeding that requires a second intervention, or is
unexpected and prolonged and/or sufficiently large to cause
haemodynamic instability.110 Secondly, the management of bleeding is
anchored on general measures like fluid resuscitation, red blood cell
transfusion, as well as the most important feature, the diagnosis,
and the treatment of the bleeding site (Table 6).111
Bleeding risk stratification should be considered as an integral
part of anticoagulation treatment decision-making, and the
HAS-BLED score112 is a simple practical score which is well
validated in various settings. In keeping with international guideline
recommendations, the HAS-BLED score should be used for bleeding
risk assessment.113 There is scarce information about its use for
assessing bleeding risk during interventional procedures. In this
setting, the BNK Online bRiDging REgistRy (BORDER) about
bridging therapy in patients undergoing oral anticoagulation showed
that HAS-BLED score was highly predictive of haemorrhagic
Aspirin, clopidogrel, ticlopidine, and prasugrel inhibit platelet function
for the lifetime of the platelet, so its inhibition takes 7 – 10 days to
resolve until new platelets are produced. On the other side, ticagrelor is
a reversible inhibitor, so platelet function normalizes after drug
clearance, but the AP effect persists for 3 – 5 days.115
Bleeding in patients while taking antiplatelet therapy should be
managed with general haemostatic measures and cessation of the
treatment should be done after a carefully assessment of the
thrombotic risk [e.g. drug-eluting stent (DES) placed ,3 months].116
Platelet transfusion may be considered in case of critical or
lifethreatening bleeding, but it is important to note that circulating
drug or its active metabolites could inhibit transfused platelets.
For non-urgent antiplatelet agent reversal, discontinue them for
5 – 7 days.115
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Vitamin-K antagonists (e.g. warfarin, acenocoumarol, or phenprocoumon)
In case of minor or self-limiting bleeding, withholding oral
anticoagulation could be sufficient. In case of moderate bleeding, 10 mg of
vitamin K can be given intravenously in order to induce a rapid
INR reduction (6 – 8 h), and prothrombin complex concentrates
(PCCs) are only added in case of severe bleeding (25 – 50 U/kg).
Recombinant activated factor VII (rFVIIa) is not recommended due to
its high rate of thrombotic complications.116,117
Unfractioned heparin and low-molecular-weight heparin
Protamine sulphate will fully reverse the effect of unfractioned
heparin (1 mg per 80 – 100 units), whereas in the case of LMWH,
protamine will only reverse about 60% of LMWH, so its effectiveness is
very limited and only in the first hour after LWWH administration.
Prothrombin complex concentrate or rFVIIa would be
recommended in life-threatening bleeding.116
Non-vitamin K antagonist oral anticoagulants (i.e. dabigatran, rivaroxaban, apixaban, and edoxaban)
Owing to the short half-life of these drugs, withholding the next
dose would be enough for all mild or self-limiting bleeding. It is
important to note the timing of the last pill intake. Consider activated
charcoal the two first hours after pill intake. Regarding moderate
bleeding, general local haemostatic measures and fluid replacement
should be undertaken. If the patient is taking dabigatran, it is
important to maintain diuresis and dialysis could be considered. In case of
severe or life-threatening bleeding, PCC at 25 U/kg can be
considered (but there is no clinical evidence), whereas activated PCC or
rFVIIa do not provide additional clinical evidence and the rate of
thrombotic complications is higher.71,118
Ongoing studies with direct specific antidotes to the NOACs show
promising results (idarucizumab for dabigatran, andexanet alfa for the
F.Xa inhibitors, aripazine for factor II, and FXa inhibitors), and these
direct antidotes should be licensed in the near future.119 – 121
Patient’s values and preferences
Clinical guidelines for the management of cardiac arrhythmias
increasingly advocate attention to patient values and preferences.18,40
Most of the recent focus has been on AF where discussing with the
patient on balancing individual stroke risk against bleeding risk
associated with oral anticoagulation is part of clinical management and
should be integral to the consultation. As clinicians, we should be
aware that patient beliefs about their health, their medical
conditions, treatment options, and healthcare they receive are key
determinants of whether or not treatment is acceptable to the patient,
and is highly relevant where antithrombotic therapy is required,
and (for example) in AF would require life-long treatment
adherence.123 Patients and physicians have different priorities when
thromboprophylaxis is considered. Patients are desperate to avoid
a stroke, regarding such an outcome as a fate worse than
death.124,125 In contrast, physicians placed more emphasis on
avoiding bleeding, even if the patient was at risk of stroke. In the study
by Lahaye et al.,124 for example, patients were willing to initiate
anticoagulation for a minimum annual absolute risk reduction of 0.8%
(number needed to treat ¼ 125) and a 15% relative risk reduction
in stroke, and would be prepared to suffer 4.4 major bleeds in order
to prevent one stroke. Other similar studies focused on patients’
preferences for thromboprophylaxis have been published.126 – 128
We need to emphasize that when considering antithrombotic
therapy in the context of arrhythmias and electrophysiological
procedures, patients do prefer informative discussions to include
individual risk information rather than generic risk.129
Perceptions of risk can be modified considerably by the way in
which risk information (benefits and side effects) are presented
and explained. Many patients with AF have limited knowledge about
their condition and lack understanding of the risks and benefits of
using antithrombotic therapy.130 – 132 Educational intervention can
help, as evident by a recent randomized trial showing much
improved knowledge and better quality of anticoagulation control,
when compared with usual care.133
Health economic considerations
Interventional procedures have the aim to reduce symptoms,
morbidity, and possibly, mortality related to arrhythmic events. As
shown in cost of illness studies, many arrhythmic conditions induce
substantial costs and appropriate interventions may have a positive
impact on disease-related hospitalizations, with a consequent
favourable economic profile in terms of cost-effectiveness at mid or
long term, in the perspective of healthcare systems.134 – 137
Atrial fibrillation is a costly disease, both in terms of direct and
indirect costs, the former being reported as per-patient annual costs in
the range of $2000 – 14 200 in North America and of E450 – 3000 in
Europe.137 The main drivers of costs are arrhythmia-related
hospitalizations and stroke events. In AF, OACs are prescribed at long term
(to reduce AF-related thromboembolic risk) and acutely during the
ablation procedure in order to reduce thromboembolic events, but
they carry the risk of haemorrhagic complications which can be
serious and absorb important economic resources.138 In other
procedures (ablation of supraventricular or ventricular tachyarrhythmias),
the use of antithrombotics, as related to the arrhythmic conditions,
is usually related to the time of the procedure or a short period after
the intervention. In CIEDs, appropriate management of
antithrombotics during implants or replacements has a crucial role for minimizing
complications, risks, and consequently, costs of the procedure.105
In general, any adverse event (i.e. haemorrhage, haematoma,
thromboembolic complication, cardiac tamponade, vascular
damage, etc.) is the result of complex interactions including patient
characteristics and co-morbidities, type and dosing of antithrombotics,
technical aspects of the interventional procedures, and operator’s
experience.134,139 The cost of complications is related to increased
direct costs (lengthening of hospitalization, need for additional
diagnostic tests, need for surgical interventions, induction of new
hospital admissions, or in-office visits) as well as direct non-medical
costs and indirect costs (loss of productivity).134,136 It is worthy
to stress that any added day of in-hospital stay has huge costs,
ranging from $476 – 835 in European countries to $4287 (on average) in
Concurrent antiplatelet therapy
Many of the patients who are referred for ablation procedures or
CIEDs are treated with single or dual antiplatelet therapy (DAPT),
due to concurrent coronary heart disease. In some patients,
antiplatelet therapy may be used in combination with OACs, and the
reader is referred to the recent joint European consensus document on
this topic, endorsed by HRS and APHRS.141
Discontinuation of concurrent antiplatelet before the implantation
of CIED may increase the thromboembolic risk. In patients who
are receiving aspirin for the secondary prevention of cardiovascular
disease and require surgery, cessation of aspirin is usually not
recommended.86,142 A large meta-analysis in almost 50 000 patients
investigating peri-procedural cessation vs. continuation of aspirin
revealed a 1.5-fold increased risk of peri-procedural bleeding
complications in patients receiving aspirin, however, without any increase
in severe bleeding.143 On the other hand, it has been reported that
peri-procedural withdrawal of aspirin in patients with coronary
artery disease was associated with a three-fold increase in major
adverse cardiac events.141 Accordingly, aspirin should be continued
for secondary prevention during most CIED implantations. Only if
the individual bleeding risk outweighs the potential cardiovascular
benefit for secondary prevention, discontinuation of aspirin 5 – 7
days before the procedure should be considered. In patients on
aspirin for primary prevention, aspirin should be stopped 5 days
Dual antiplatelet therapy
There are no randomized trials studying withdrawal vs. continuation
of DAPT before CIED implantations; however, there are some data
from cohort studies. In most of these studies (Table 7),109,144 – 147,149
dual therapy with aspirin and clopidogrel increased the risk of
bleeding after EPD implantations compared with aspirin alone. Only the
study by Dreger et al.107 did not demonstrate any increased risk of
bleeding complications in DAPT patients, but in this study a vacuum
drainage system was applied to all patients.
In patients receiving DAPT due to a coronary stent or a recent
acute coronary syndrom (ACS), current guidelines recommend
deferring surgery until DAPT is no longer necessary.86,143 If delaying
surgery is not possible, it is recommended to stop clopidogrel 5
days before surgery, but consider resuming clopipogrel as soon as
possible after the procedure. We recommend this procedure also
for CIED implantations. The exception is if a coronary stent has
been implanted within 30 days [bare metal stent (BMS)] or 3 months
(new-generation DES), and it is not possible to defer the
implantation, then the procedure should be performed on continued
DAPT. Apparently, coronary stenting procedures should better
follow implantation of a CIED whenever possible. In patients who are
on oral anticoagulation in addition to DAPT, special considerations
apply with respect to a minimum duration of DAPT.141
In the setting of CIED implantation, there are no data with the
newer antiplatelet agents prasugrel or ticagrelor. There may be
similar or even higher bleeding risk with these agents compared with
clopidogrel, but until more data are available, the management
approach should be similar to clopidogrel, if deferring implantation
is not possible.
Patients undegoing cardiac implantable electronical device implantation while being treated with antiplatelet therapy: consensus recommmendations
In patients on single antiplatelet therapy (aspirin or clopidogrel) for
secondary prevention, it is recommended to continue aspirin during
In patients on DAPT (i.e. aspirin plus clopidogrel or other P2Y12 agent)
requiring device surgery within 4 weeks of BMS or within 6 months
of DES implantation (within 3 months with new-generation DES), it
is recommended to continue both AP agents.
In patients on DAPT, it should be considered to defer elective device
implantations until DAPT is no longer necessary.
In patients on DAPT after ACS requiring device surgery .4 weeks
after BMS implantation or .6 months after DES (.3 months after
new-generation DES), it should be considered to stop the P2Y12
inhibitor for 5 – 7 days before surgery, but consider resuming a
P2Y12 inhibitor as soon as possible after the procedure. A
multidisciplinary approach for the individual patient is
Ablation procedures in patients on antiplatelet therapy
For the introduction and manoeuvring of sheaths and catheters, the
risk of peripheral bleeding or complications when using aspirin and/
or clopidogrel is low.1 However, most patients with AF or atrial
flutter are treated with oral anticoagulation in addition to DAPT, and
the risk of bleeding with DAPT in addition to oral anticoagulation
is known to be much higher.150
The other problem may be the management of cardiac
tamponade or pericardial effusion because of perforation when the patient
is on DAPT. There are no relevant data in the literature on this
specific question; therefore, no definite answer can be given. However,
it can be assumed that bleeding is more severe and more difficult to
be managed when the patient is on DAPT. This is especially the case
if the patient is on oral anticoagulation in addition to DAPT, as in AF
and atrial flutter. It is therefore recommended to postpone ablation
of AF to a time when DAPT can be safely discontinued.
Patients undergoing the ablation procedure while being treated with antiplatelet therapy: consensus recommendations
In patients on single antiplatelet therapy (aspirin or clopidogrel) for
secondary prevention, it is recommended to continue aspirin during
the ablation procedure.
In patients on DAPT in addition to OAC, it is recommended to defer
ablation procedures until DAPT is no longer necessary.
In patients on DAPT, it may be considered to continue DAPT during
right-sided procedures and uncomplicated left-sided procedures.
In patients on single antiplatelet therapy (aspirin) in addition to OAC, it
should be considered to continue aspirin during the procedure.
The antithrombotic management of patients undergoing
electrophysiological procedures has witnessed major changes due to an
increase in the number of procedures and in the knowledge about the
role of VKAs and NOACs. Thus, therapy with VKA is usually not
interrupted in patients undergoing ablation procedures like PVI.
Likewise, patients on VKA requiring implantation of a CIED are operated
on a VKA unless they are at very low risk for a thromboembolic
event. In this case, VKA can be paused and reinitiated after surgery
without heparin bridging. The formerly commonly practiced
‘bridging therapy’ with unfractionated heparin or LMWH must not be
used since it significantly increases bleeding complications.
At the same time, numerous NOACs have been approved for the
prevention of thromboembolic complications in patients with
nonvalvular AF, or with a previous pulmonary embolism or deep vein
thrombosis. As patients undergoing electrophysiological
procedures are increasingly treated with these agents, our knowledge
about their use is increasing future adjustments in the current
consensus recommendations are likely.
Supplementary material is available at Europace online.
EHRA Scientific Documents Committee: Gregory Y.H. Lip (EHRA
Scientific Documents Committee Chair), Bulent Gorenek
(EHRA Scientific Documents Committee Co-Chair), Christian
Electrocautery in all patients,
vacuum drainage systems in all
Low number of patients on DAPT
(n ¼ 25)
Sticherling, Laurent Fauchier, Hein Heidbuchel, Angel Moya Mitjans,
Mark A. Vos, Michele Brignole, Gheorghe-Andrei Dan, Michele
Gulizia, Francisco Marin, Giuseppe Boriani, Deirdre Lane, and Irene
Conflict of interest: Detailed conflict of interest statement is
available as Supplementary material online.
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