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Apixaban, Rivaroxaban, and Dabigatran in Patients Undergoing Atrial

Fibrillation Ablation

Andreas Rillig, M.D.; Tina Lin, M.B.B.S., B.Med.Sci., F.R.A.C.P.; Joaquina Plesman; Christian-H. Heeger, M.D.; Christine Lemes, M.D.;
Andreas Metzner, M.D.; Shibu Mathew, M.D.; Erik Wissner, M.D.; Peter Wohlmuth; Feifan Ouyang, M.D.; Karl-Heinz Kuck, M.D., F.E.S.C.,
F.H.R.S.; Roland Richard Tilz, M.D.
J Cardiovasc Electrophysiol. 2016;27(2):147-153.

Abstract and Introduction

Abstract

Periprocedural Anticoagulation in AF Ablation. Introduction: Data on the novel oral anticoagulants (NOACS) during catheter
ablation (CA) of atrial fibrillation (AF) are still limited. This study evaluated the periprocedural major complications (MC) of CA of
AF, and compared Apixaban, Dabigatran, and Rivaroxaban with continuous phenoprocoumon.
Methods and Results: A total of 444 patients (mean age = 65.1 9.4 years; 283 [64%] male) with paroxysmal (n = 180 [41%]),
persistent (n = 256 [58%]), or longstanding-persistent AF were enrolled. CA was performed in all patients using radiofrequency
energy in conjunction with a 3D-mapping system. MCs were defined according to the current guidelines. Continuous
phenprocoumon-therapy was administered in 120/444 (27%) patients (group 1) and 324/444 (73%) patients were treated with
NOACs (group 2; Dabigatran: n = 51 [15.7%]; Rivaroxaban: n = 193 [59.6%]; Apixaban: n = 80 [24.7%]). Procedure times were
comparable between groups 1 and 2 (128.2 39.7 minutes vs. 129.7 51.2 minutes; P = 0.77). CHA2DS2-Vasc (3.0 [2.0, 4.0)] vs.
2.0 [1.0, 3.0]; P < 0.01) and HASBLED scores (2.0 [2.0, 2.5] vs. 2.0 [1.0, 2.0]; P = 0.002) were higher in group 1 patients. The
incidence of MCs in the overall group was 8/444 (2%) and was equally distributed between groups 1 and 2 (2/120 [2%] vs. 6/324
[2%], P = 0.90). The incidence of MCs was comparable between the three different NOACs. There were no significant differences
between patients with and without MCs with regard to age, CHA2DS2-Vasc-score or HASBLED-score.
Conclusions: The major complication rate between all three NOACs currently available and continuous phenprocoumon during
AF ablation seem to be comparable. Complication rates were similar between patients treated with the three different available
NOACs.
Introduction

Although well established as an effective treatment option,[14] catheter ablation of symptomatic atrial fibrillation (AF) is still
associated with a significant number of potential periprocedural complications, including bleeding complications such as groin
hematoma, pericardial effusion, or tamponade.[5,6] However, oral anticoagulation (OAC) is still the only medical therapy to reduce
the risk of stroke in patients with AF and is also of particular importance in patients after AF ablation.[7,8] Since the introduction of
the novel oral anticoagulants (NOACs),[911] there is currently still controversy over whether catheter ablation for AF in patients
treated with NOACs has a comparable safety profile compared to other anticoagulants.[1214] Recent studies have shown that AF
ablation can be performed safely without discontinuation of phenprocoumon;[1517] however, data on the periprocedural
management of NOACs are still limited and require further evaluation.[12,18,19]
This study reports on the complication rates during AF ablation procedures in patients treated with Apixaban, Dabigatran, and
Rivaroxaban, and compared this to patients treated with continuous phenprocoumon in a high volume center.

Methods

Data from our complication ablation registry were collected between October 2013 and October 2014. All patients who underwent
AF ablation using radiofrequency (RF) energy in conjunction with a 3D-mapping system and treated with NOACs or continuous
phenprocoumon were analyzed. The anticoagulation regimen and the complications identified were assessed in all patients.
In all patients, transesophageal echocardiography was performed prior to catheter ablation of AF to assess LV systolic function and
to exclude intracardiac thrombus.
Pericardial effusion was excluded via transthoracic echocardiography directly after the ablation procedure, as well as on day-1
postablation.

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A pressure bandage over the femoral vein puncture site was applied for a minimum of 12 hours after sheath removal.
This registry was approved by the local institutional review board and conforms to the Declaration of Helsinki of 2008. All authors
had full access to the data, and have read and agreed to the manuscript as written.
Electrophysiological Study and Left Atrial 3D-mapping

Our ablation approach has been described previously in detail.[1,2] In brief, after written informed consent, all procedures were
performed under deep sedation with midazolam, fentanyl, and a continuous infusion of propofol. In all patients, double transseptal
puncture using a modified Brockenbrough technique were used with the insertion of two SL1 sheaths (St. Jude Medical,
Minneapolis, MN, USA) into the left atrium (LA). After introduction of both sheaths into the LA, intravenous heparin was
administered, targeting an activated clotting time (ACT) of >250 seconds. ACT levels were checked every 30 minutes and
maintained above 250 seconds using appropriate intravenous boluses of unfractionated heparin. Transseptal sheaths were
continuously flushed with heparinized saline to prevent thrombus formation. One SL1 sheath was used for a spiral diagnostic
decapolar mapping catheter (Lasso, Biosense Webster, Diamond Bar, CA, USA). In all patients, a three-dimensional
electroanatomical map of the LA was created in combination with either the CARTO mapping system or the NavX/Ensite
Velocity mapping system using a conventional irrigated-tip ablation catheter (ThermoCool Navi-Star, Biosense Webster) via
the second SL1 sheath. Selective angiography of each pulmonary vein (PV) using right anterior oblique (RAO) 30 and left anterior
oblique (LAO) 40 fluoroscopic views were then performed.
Ablation Protocol

All patients underwent circumferential PV isolation (CPVI) using irrigated RF energy, with a maximum temperature of 43 C, a
maximal power of 40 W, and an infusion rate of 1725 mL/min. At the posterior LA wall, power was limited to a maximum of 30 W.
The endpoint of PVI was defined as the absence of any PV spike potential recorded on the spiral mapping catheter after a waiting
period of at least 30 minutes after PVI was achieved. In redo ablation procedures, the initial strategy was assessment of PV
reconduction. If reconduction was found, RF energy was applied to close all PV conduction gaps, aiming for electrical reisolation.
Periprocedural Anticoagulation Regimen

In patients on preprocedural phenprocoumon therapy, continuation of phenprocoumon was recommended with a target INR of 23.
Postprocedural OAC therapy in patients on phenprocoumon targeted an international normalized ratio (INR) of 23.
In patients treated with NOAC therapy, the last dose of NOAC was given 2 days prior to the ablation procedure and was restarted 6
hours after sheath removal as follows: Apixaban 2.5 mg, Dabigatran 75 mg, Rivaroxaban 10 mg followed by full therapeutic dose
next day in the morning. No bridging with low-molecular-weight heparin was administered (Fig. 1).

Figure 1.

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Periprocedural management of NOAC therapy.

Complications

All complications were defined as recommended by the current EHRA guidelines.[7] Complications were considered to be major if
they resulted in permanent injury or death, required intervention for treatment, or resulted in prolonged hospitalization for more than
48 hours. Bleeding complications were considered major if they required blood transfusion or resulted in a 20% or greater fall in the
hemoglobin (Hb) level.[7] These included groin hematomas requiring transfusion or surgical intervention as well as pericardial
effusions requiring drainage. All clinical thrombembolic events such as stroke, TIA, or arterial embolism were defined as a major
complication.
Statistics

Continuous data were described as means and standard deviations, if the variables were normally distributed, or as medians, first
and third quartiles otherwise. Differences of metric variables between anticoagulation regimens were analyzed with analysis of
variance, if the data were approximately normally distributed, and with KruskalWallis test for non-normally distributed data.
Categorical data were described with absolute and relative frequencies. Differences between categorical variables were evaluated
with the chi-square test or with Fisher's exact test for small, expected cell frequencies.
If three or more groups were compared and the overall tests for group effects were significant, two-group comparisons were
performed using permutation tests for P-value adjustment.
All P-values were two-sided. For overall tests P < 0.05 was considered significant and for multiple comparisons adjusted P-values
were calculated. All calculations were performed with the statistical analysis software SAS (SAS Institute Inc., version 9.3, Cary,
NC, USA).

Results

Baseline Characteristics

The baseline characteristics of the overall patient group are displayed in .

Table 1. Baseline Characteristics of the Overall Population for the Different Anticoagulation Regimens

Variable

Age (years)
Male, n (%)
BMI

Structural heart disease, n

(%)
Hypertension, n (%)
Diabetes, n (%)

Prior stroke/TIA, n (%)

Paroxysmal AF, n (%)
Persistent AF, n (%)

LS-persistent AF, n (%)

CHA2DS2VASc-score
HASBLED-score

Overall N N =
444

Continuous Pheprocoumon Group

(Group 1) N = 120

283 (64%)

70 (58%)

65.1 9.4

66.7 8.8

NOAC Group (Group 2)

P-Value
N = 324

64.6 9.6

0.033
1.00

213 (66%)

0.15

28.1 11.8

28.1 4.2

28.1 13.6

141 (32%)

46 (38%)

95 (29%)

0.070

298 (67%)

92 (77%)

206 (64%)

0.009

36 (8%)

13 (11%)

23 (7%)

0.20

55 (12%)

16 (13%)

180 (41%)
256 (58%)
8 (2%)

2.0 (1.0, 3.0)

2.0 (1.0, 2.0)

39 (12%)

51 (43%)

129 (40%)

6 (5%)

2 (1%)

63 (53%)
3.0 (2.0, 4.0)
2.0 (2.0, 2.5)

193 (60%)
2.0 (1.0, 3.0)
2.0 (1.0, 2.0)

0.71
0.61
0.18

0.002

<.001
0.002

AF = atrial fibrillation; LS-persistent AF = longstanding-persistent AF; BMI = body mass index; TIA = transient ischemic attack.
Values expressed as n (%), mean standard deviation, or median (25th, 75th percentiles). P-value comparisons across

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anticoagulation regimens are based on the chi-square test for categorical variables; P-values for continuous variables are based on
ANOVA or KruskalWallis test for median.
The distribution of NOACs in the group 2 patients (NOAC therapy pre- and postablation) was as follows:
Dabigatran (n = 51, 15.7%), Rivaroxaban (n = 193, 59.6%), and Apixaban (n = 80, 24.7%).
The dosage regimens of the different NOAC groups were the following:
Dabigatran 220 mg: 14/51 (27%), Dabigatran 300 mg: 37/51 (73%), Rivaroxaban 15 mg: 17/193 (9%), Rivaroxaban 20 mg:
176/193 (91%), Apixaban 5 mg: 2/80 (2%), Apixaban 10 mg: 78/80 (98%).
The baseline characteristics of patients treated with NOACs are displayed in . Patients on Dabigatran had significantly more often a
history of stroke (P = 0.044) and patients on Apixaban had significantly more often a history of structural heart disease (P = 0.006).
Table 2. Baseline Characteristics of Patients Treated Only with NOACs (Group 2)

Variable

Overall N = 324 Rivaroxaban N = 193 Apixaban N = 80 Dabigatran N = 51 P-Value

Age (years)
Male, n (%)

64.6 9.6

64.8 9.7

64.1 10.2

64.3 8.6

0.83

28.1 13.6

28.9 17.3

26.9 4.5

27.0 4.2

0.45

206 (64)

127 (66)

44 (55)

35 (69)

23 (7)

16 (8)*

213 (66)

BMI

Structural heart disease, n (%)

95 (29)

Hypertension, n (%)
Diabetes, n (%)

39 (12)

Prior stroke/TIA, n (%)

Paroxysmal AF, n (%)

129 (40)

Persistent, n (%)

LS-persistent AF, n (%)

HASBLED-score

44 (23)*
24 (12)

33 (41)*
9 (11)

2.0 (1.0, 2.0)

18 (35)

0.006

6 (12)

0.96

0.17

0.044

46 (57.5)

38 (75)

0.06

0 (0)

2.0 (1.0, 3.0)

0.1

6 (12)**

2 (1)

2.0 (1.0, 3.0)

37 (73)

1 (1)*,**

34 (42.5)

109 (56)

2.0 (1.0, 2.0)

45 (56)

82 (42)

193 (59)
2 (1)

CHA2DS2VASc-score

131 (68)

13 (25)

2.0 (1.0, 3.0)

2.0 (1.0, 2.0)

(0)

2.0 (2.0, 3.0)

2.0 (2.0, 2.0)

0.08
0.51
0.67
0.05

*,**Symbols indicate significant differences between groups.

AF = atrial fibrillation; LS-persistent AF = longstanding-persistent AF; BMI = body mass index; TIA = transient ischemic attack.
Values expressed as n (%), mean standard deviation, or median (25th, 75th percentiles). P-value comparisons across
anticoagulation regimens are based on the chi-square test for categorical variables; P-values for continuous variables are based on
ANOVA or KruskalWallis test for median.
Procedural and Anticoagulation Details

Procedural and anticoagulation details of the two anticoagulation groups are presented in .
Table 3. Procedural and Anticoagulation Details of the Overall Population

Variable

Overall N =
444

Continuous Phenprocoumon Group (Group

1) N = 120

8 (2%)

Proc duration (minutes) 129.3 48.4

Major complications, n
(%)
INR at hospital
admission

INR at discharge

128.2 39.7

NOAC Group (Group 2) N

P-Value
= 324

129.7 51.2

0.77

2 (2%)

6 (2%)

0.90

1.1 (1.0, 2.0)

2.3 (2.1, 2.5)

1.1 (1.0, 1.2)

<.001

2.5 0.5

2.5 0.5

n.a.

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ASA therapy, n (%)

Clopidogrel therapy, n
(%)
ACT min (s) (proc)

ACT max (s) (proc)

7 (2%)

2 (2%)

5 (2%)

0.93

4 (1%)

0 (0%)

4 (1%)

0.22

193.0 78.2

229.7 91.6

179.6 68.1

<.001

348.5 68.3

388.3 53.8

333.9 67.3

<.001

INR = international normalized ratio; ASA = acetylic salicylic acid; ACT = activated clotting time. Values expressed as n (%), mean
standard deviation, or median (25th, 75th percentiles). P-value comparisons across anticoagulation regimens are based on the
chi-square test for categorical variables; P-values for continuous variables are based on ANOVA or KruskalWallis test for median.
The number of redo procedures was higher in group 1 (n = 58/120 [48%]), as compared to group 2 (n = 112/324 [35%]), but was
similar in the different NOAC subgroups (Rivaroxaban n = 63/193 [33%], Apixaban n = 32/80 [40%], Dabigatran 17/51 [33%], P =
0.5).
Procedural and anticoagulation details of patients treated with NOACs are displayed in .
Table 4. Procedural and Anticoagulation Details of Patients Treated Only with NOACs (Group 2)

Variable

Procedure duration (minutes)

Overall N = 324 Rivaroxaban N = 193 Apixaban N = 80 Dabigatran N = 51 P-Value

129.7 51.2

128.8 56.7

130.2 46.0

132.2 35.5

0.91

INR at hospital admission

1.1 (1.0, 1.2)

1.1 (1.0, 1.2)*

1.0 (1.0, 1.1)

1.0 (1.0, 1.1)*

0.006

Clopidogrel therapy, n (%)

4 (1)

0 (0)*

2 (3)

2 (4)*

0.039

354.6 43.6*,**

0.005

Major complications, n (%)

ASA therapy, n (%)
ACT min (seconds)

ACT max (seconds)

6 (2)
5 (2)

179.6 68.1
333.9 67.3

3 (2)
4 (2)

184.0 65.5

335.9 60.7*

2 (3)
1 (1)

175.0 85.2

315.7 88.5**

1 (2)
0 (0)

170.1 43.5

0.87
0.55
0.34

INR = international normalized ratio; ASA = acetylic salicylic acid; ACT = activated clotting time. *,**Symbols indicate significant
differences between groups.
Values expressed as n (%), mean standard deviation, or median (25th, 75th percentiles). P-value comparisons across
anticoagulation regimens are based on the chi-square test for categorical variables; P-values for continuous variables are based on
ANOVA or KruskalWallis test for median.
Complications

The incidence of major complications in the overall group was 8/444 (2%) and was equally distributed between groups 1 and 2
(2/120 [2%] vs. 6/324 [2%], P = 0.90) ().
Table 3. Procedural and Anticoagulation Details of the Overall Population

Variable

Overall N =
444

Continuous Phenprocoumon Group (Group

1) N = 120

8 (2%)

Proc duration (minutes) 129.3 48.4

Major complications, n
(%)
INR at hospital
admission

INR at discharge

ASA therapy, n (%)

Clopidogrel therapy, n
(%)

129.7 51.2

0.77

2 (2%)

6 (2%)

0.90

1.1 (1.0, 2.0)

2.3 (2.1, 2.5)

1.1 (1.0, 1.2)

<.001

2.5 0.5

2.5 0.5
2 (2%)

n.a.

5 (2%)

0.93

4 (1%)

0 (0%)

4 (1%)

0.22

7 (2%)

128.2 39.7

NOAC Group (Group 2) N

P-Value
= 324

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ACT min (s) (proc)

ACT max (s) (proc)

193.0 78.2

229.7 91.6

348.5 68.3

179.6 68.1

388.3 53.8

333.9 67.3

<.001
<.001

INR = international normalized ratio; ASA = acetylic salicylic acid; ACT = activated clotting time. Values expressed as n (%), mean
standard deviation, or median (25th, 75th percentiles). P-value comparisons across anticoagulation regimens are based on the
chi-square test for categorical variables; P-values for continuous variables are based on ANOVA or KruskalWallis test for median.
There were no statistically significant differences between patients with (8/444 (2%)) and without major complications (436/444
[98%]) with regard to age (71.5 [68.575.0] years vs. 67.0 [59.073.0] years; P = 0.093), CHA2DS2-Vasc-score (3 [24] vs. 2 [13];
P = 0.13) and HASBLED-score (2 [12.5] vs. 2 [12]; P = 0.31).

No difference in major complications was observed between patients of the different NOAC groups (Dabigatran, Rivaroxaban,
Apixaban) ().
Table 4. Procedural and Anticoagulation Details of Patients Treated Only with NOACs (Group 2)

Variable

Procedure duration (minutes)

Overall N = 324 Rivaroxaban N = 193 Apixaban N = 80 Dabigatran N = 51 P-Value

129.7 51.2

128.8 56.7

130.2 46.0

132.2 35.5

0.91

INR at hospital admission

1.1 (1.0, 1.2)

1.1 (1.0, 1.2)*

1.0 (1.0, 1.1)

1.0 (1.0, 1.1)*

0.006

Clopidogrel therapy, n (%)

4 (1)

0 (0)*

2 (3)

2 (4)*

0.039

354.6 43.6*,**

0.005

Major complications, n (%)

ASA therapy, n (%)
ACT min (seconds)

ACT max (seconds)

6 (2)
5 (2)

179.6 68.1
333.9 67.3

3 (2)
4 (2)

184.0 65.5

335.9 60.7*

2 (3)
1 (1)

175.0 85.2

315.7 88.5**

1 (2)
0 (0)

170.1 43.5

0.87
0.55
0.34

INR = international normalized ratio; ASA = acetylic salicylic acid; ACT = activated clotting time. *,**Symbols indicate significant
differences between groups.
Values expressed as n (%), mean standard deviation, or median (25th, 75th percentiles). P-value comparisons across
anticoagulation regimens are based on the chi-square test for categorical variables; P-values for continuous variables are based on
ANOVA or KruskalWallis test for median.
The following major complications were identified:
Phenprocoumon group (group 1: n = 2/120, 2%): In one patient, femoral artery aneurysm occurred that required thrombin
injection. In another patient, a groin hematoma associated with a Hb drop >20% was observed, not requiring transfusion. In
this patient, phenprocoumon therapy was continued despite the development of the hematoma (INR 2.09 prior to the
procedure and 2.95 at hospital discharge).
NOAC group (group 2: n = 6/324, 2%): Three patients developed pericardial effusion requiring drainage and one had acute
pericardial tamponade. One patient developed groin hematoma associated with a Hb drop >20% requiring transfusion (two
red blood cell concentrates). In another patient, pulmonary embolism occurred leading to prolonged hospital stay >48 hours.
In the patient with acute pericardial tamponade during the ablation procedure (Rivaroxaban group), 1200 mL of blood was
aspirated after subxiphoidal pericardial puncture. The pigtail catheter was removed the next day, and full dose Rivaroxaban (20
mg) was reinitiated in the evening of the first day after the procedure.
In the second patient, pericardial effusion was detected on TTE 4 hours after the procedure and therefore 2 hours before initiation
of the reduced NOAC dose according to our regimen. Following pericardial puncture, 500 mL of blood was aspirated. Lowmolecular-weight heparin was administered during the subsequent days and Dabigatran was started on the morning of the fourth
day after the ablation procedure (150 mg b.i.d.).
In the third patient, half dose Apixaban (2.5 mg) was reinitiated 6 hours after the procedure and full dose Apixaban in the morning
of the next day (day 1 after the procedure) according to our protocol. In the subsequent day 1 TTE, a pericardial effusion was seen
with signs of hemodynamic compromise requiring pericardial puncture (extraction of 400 mL blood). After the pigtail was removed,
low-molecular-weight heparin was administered and Apixaban was reinitiated on the evening of day 5 after the ablation procedure.

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The fourth patient was treated with Rivaroxaban according to our anticoagulation protocol and discharged on the second day after
the ablation procedure, after exclusion of pericardial effusion on TTE was performed. Two days after discharge, the patient
experienced mild dyspnea during exertion and the general practitioner diagnosed pericardial effusion. The patient was readmitted
to our hospital and monitored in our intensive care unit. Due to progressive worsening of the pericardial effusion with the
development of signs of hemodynamic compromise, pericardial puncture was performed on day 8 after the procedure (extraction of
900 mL blood). Thereafter, the patient was monitored for another 7 days in our hospital and low-molecular-weight heparin was
administered until discharge. After exclusion of recurrence of pericardial effusion on TTE, the patient was discharged on
Rivaroxaban 20 mg once daily.
In the patient with groin hematoma and significant Hb drop, Apixaban was administered according to our anticoagulation protocol.
Significant Hb drop was confirmed on the 3rd day after the ablation procedure, and Apixaban was withheld and low-molecularweight heparin was administered thereafter. Apixaban was reinitiated on the 6th day after the ablation procedure (5 mg b.i.d.).
In the patient with pulmonary embolism, the anticoagulation regimen after the ablation procedure was followed according to our
protocol (Rivaroxaban group). The patient complained of dyspnea the day after the procedure. Diuretic therapy was initiated as
pulmonary congestion was suggested as the cause for dyspnea. As the symptoms did not resolve, a CT-scan was performed on
the 4th day after the ablation procedure, with confirmation of pulmonary embolism. Since then, the patient was treated with
Rivaroxaban 15 mg b.i.d. according to the current recommendations.

Discussion

The main findings of the present study are:

1. The complication rate was comparable between patients on NOACs and patients on continuous phenprocoumon therapy
using our institutional periprocedural anticoagulation protocol.
2. The incidence of major complications in patients treated with Dabigatran, Rivaroxaban. or Apixaban was comparable
between the 3 groups.
Distribution and Complication Rate of Different Anticoagulation Regimens

The minority of patients referred for AF ablation in our high volume center were treated with continuous phenprocoumon (27%),
whereas the majority was treated with NOACs (73%). The majority of patients treated with NOACs were treated with Rivaroxaban,
followed by Apixaban and Dabigatran. Of note, patients with continuous phenprocoumon were older than patients treated with
NOACs, a phenomenon which is commonly seen in AF populations.[20]
The efficacy and safety of continuous warfarin have been shown recently in the prospective and randomized COMPARE study.[21]
Continuous warfarin was associated with a similar incidence of bleeding complications but with a higher risk of thrombembolic
events.[21] Therefore, continuous warfarin or phenprocoumon is currently preferred over phenprocoumon discontinuation and
bridging with low-molecular-weight heparin.[20]
Complication Rate on NOAC Therapy

Periprocedural anticoagulation with oral vitamin K antagonists has been well established as an effective treatment strategy to
reduce the risk of thromboembolic sequelae secondary to catheter ablation of AF.[7,16,22] The introduction of the NOACs has raised
several concerns in the peri-procedural management of AF ablation, and one of the leading issues is the lack of the possibility of
antagonization. Currently, the periprocedureal management of NOACs has not yet been standardized and varies significantly
amongst different centers.[2325] To date, limited data have been published that evaluate the periprocedural safety of
anticoagulation with the NOACs in patients undergoing AF ablation procedures.[12,18,21,26,27] Whereas some data exist for AF
ablation when using Dabigatran,[26,28,29] only limited data are available for the other NOACs Rivaroxaban[18] and Apixaban.[19] In
addition, limited data are available that compare the efficacy and safety of anticoagulation regimens that use traditional Vitamin K
antagonists and that use NOACs.
In our present ablation registry, the last NOAC dose was administered 2 days prior to the ablation procedure and was independent
of the CHAD2DS2-VASc-score or the renal function. The NOACs were then restarted 6 hours postablation at a half dose, then at a

full dose the next day. This periprocedural anticoagulation strategy is currently only being used in a minority of centers in Europe[24]
and data are therefore lacking. As demonstrated in our registry, the proposed peri-procedural management strategy with each of
the NOACs Dabigatran, Rivaroxaban, and Apixaban is safe and comparable with regard to major complications, between each of
the different NOACs as well as between the NOACs and continuous Phenprocoumon. Of note, all major complications were seen

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in patients who were treated with the higher dosage of the corresponding NOAC (i.e., Dabigatran 150 mg twice a day, Rivaroxaban
20 mg daily, Apixaban 5 mg twice a day). However, as the overall incidence of major complications was small, there was no
statistically significant difference in major complications between the higher dose groups compared to the lower dose groups with
respect to each of the three NOACs. Larger patient numbers are needed to confirm the hypothesis that a higher NOAC dosage is
associated with a higher risk of major complications during AF ablation.
The occurrence of pericardial effusion and tamponade was only seen in the NOAC group, whereas no effusion was seen in the
phenprocoumon group. In the current literature, the rate of pericardial effusion or tamponade was comparable between patients
treated with NOACs and uninterrupted warfarin or phenprocoumon.[18,19] Nonetheless, in our study the incidence of pericardial
effusion or tamponade in the NOAC group (4/324, 1.2%) is in line with the rate of pericardial hazards described in the current
literature.[5] Therefore, although there was a cumulative incidence of pericardial effusion/tamponade in NOAC patients in our study,
we conclude that there is no significantly increased risk for pericardial effusion or tamponade when catheter ablation for treatment
of atrial fibrillation is performed using NOACs as compared to phenprocoumon.
In one patient of the NOAC-group, pulmonary embolism occurred. To the best of our knowledge, there are no data on the
incidence of pulmonary embolisms during PVI. Basically, a pressure bandage after the procedure as well as endothelial injury after
sheath placement might enhance the risk of thrombus formation at the puncture site and therefore facilitate the occurrence of
pulmonary embolism. It is questionable whether uninterrupted NOAC use might have prevented this event.
Besides bleeding complications such as groin hematomas and pericardial effusions, the other concern in patients undergoing AF
ablation are thrombembolic events such as TIA or stroke.[30] Importantly, in patients on NOAC therapy, where the last NOAC dose
was administered 2 days prior to the procedure and restarted 6 hours postablation, no thrombembolic events occurred. This
suggests that the proposed NOAC protocol (Fig. 1) employed in our institution is feasible with regard to prevention of
thrombembolic events during AF ablation procedures. Furthermore, all three NOACs were analyzed individually in this registry and
the results for both major bleeding and thrombembolic events were comparable between Dabigatran, Rivaroxaban, and Apixaban
().
Table 4. Procedural and Anticoagulation Details of Patients Treated Only with NOACs (Group 2)

Variable

Procedure duration (minutes)

Overall N = 324 Rivaroxaban N = 193 Apixaban N = 80 Dabigatran N = 51 P-Value

129.7 51.2

128.8 56.7

130.2 46.0

132.2 35.5

0.91

INR at hospital admission

1.1 (1.0, 1.2)

1.1 (1.0, 1.2)*

1.0 (1.0, 1.1)

1.0 (1.0, 1.1)*

0.006

Clopidogrel therapy, n (%)

4 (1)

0 (0)*

2 (3)

2 (4)*

0.039

354.6 43.6*,**

0.005

Major complications, n (%)

ASA therapy, n (%)
ACT min (seconds)

ACT max (seconds)

6 (2)
5 (2)

179.6 68.1
333.9 67.3

3 (2)
4 (2)

184.0 65.5

335.9 60.7*

2 (3)
1 (1)

175.0 85.2

315.7 88.5**

1 (2)
0 (0)

170.1 43.5

0.87
0.55
0.34

INR = international normalized ratio; ASA = acetylic salicylic acid; ACT = activated clotting time. *,**Symbols indicate significant
differences between groups.
Values expressed as n (%), mean standard deviation, or median (25th, 75th percentiles). P-value comparisons across
anticoagulation regimens are based on the chi-square test for categorical variables; P-values for continuous variables are based on
ANOVA or KruskalWallis test for median.
OAC in combination with antiplatelet therapy is still a critical issue in patients with AF.[31] In this registry, only a minority of patients
were treated concomitantly with anticoagulation and antiplatelet therapy such as acetylic salicylic acid or clopidogrel (23%).
Therefore, the impact of antiplatelet therapy in combination with OAC during PVI has to be assessed in larger trials.
Clinical Implication

These results support previous studies where the NOACs have shown promising results during AF ablation procedures.[12,13]
However, as most trials have only reported on the efficacy and safety of Dabigatran and Rivaroxaban use so far,[12,13,18,21] this
registry provides and compares data on all three NOACs currently available on the market. The anticoagulation protocol used in
our institution applies to all three NOACs and has shown comparable results between the different NOACs as well as to traditional
OACs.

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Page 9 of 11

Limitations

This was a single-center observational registry. The data reflect real-world data, with an unequal patient distribution between the
different anticoagulation groups. There were also differences in patient baseline characteristics, which at least in part lead to
differences in the anticoagulation groups. Nonetheless, the data give important insights into the major complication rates of all
currently available NOACs as compared to continuous phenprocoumon during AF ablation procedures. Larger patient numbers are
needed to support these findings.

Conclusion

The major complication rate appears to be similar between Apixaban, Rivaroxaban, and Dabigatran during AF ablation. The use of
NOACs was comparable to continuous phenprocoumon therapy with regard to major complications.
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