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Meta-analysis of dabigatran vs warfarin in patients undergoing catheter ablation for atrial fibrillation
International Journal of Cardiology 189 (2015) 199–203
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Letter to the Editor
Meta-analysis of dabigatran vs warfarin in patients undergoing catheter ablation for atrial fibrillation Kevin Phan a,b,⁎, Nelson Wang b, Laurent Pison c, Narendra Kumar c, Kerry Hitos b,d, Stuart P. Thomas a,b a
Department of Cardiology, Westmead Hospital, Sydney, Australia University of Sydney, Sydney, Australia Department of Cardiology, Maastricht University Hospital, Maastricht, The Netherlands d Department of Surgery, Westmead Hospital, Sydney, Australia b c
a r t i c l e
i n f o
Article history: Received 24 January 2015 Received in revised form 25 March 2015 Accepted 9 April 2015 Available online 11 April 2015 Keywords: Catheter ablation Dabigatran Warfarin Thromboembolism VKA Systematic review
Radiofrequency catheter ablation (RFCA) is increasingly used for to treat symptomatic atrial fibrillation (AF), particularly after failure of medical therapy [1,2]. However there is substantial risk of thromboembolism perioperatively. Warfarin has traditionally been used as the anticoagulant of choice despite the significant monitoring required and the long duration of onset [3]. New oral anticoagulants (NOACs) such as apixaban, dabigatran, and rivaroxaban have been introduced as alternatives to warfarin, and act via direct inhibition of thrombin or factor Xa [4]. The current study sought to analyse the efficacy and safety of dabigatran as an anticoagulant in RFCA compared to warfarin in the setting of catheter ablation procedures. Electronic searches were performed using six electronic databases, using the terms “dabigatran”, “warfarin”, “VKA”, “ablation” and “atrial fibrillation” as keywords or MeSH headings. We included studies comparing dabigatran and warfarin for patients undergoing catheter ablation, with at least 10 patients in each cohort. When institutions published duplicate studies with accumulating numbers of patients or increased lengths of follow-up, only the most complete reports were
⁎ Corresponding author at: Department of Cardiology, Westmead Hospital, Hawkesbury Rd, Westmead, Sydney, NSW 2145, Australia. E-mail address: [email protected] (K. Phan).
http://dx.doi.org/10.1016/j.ijcard.2015.04.072 0167-5273/© 2015 Elsevier Ireland Ltd. All rights reserved.
included for quantitative assessment at each time interval. Abstracts, case reports, conference presentations, editorials, and expert opinions were excluded. Meta-analysis was performed by combining extracted data as pooled incidence of mortality or complications. The relative risk (RR) was used as a summary statistic for dichotomous variables, and weighted mean difference (WMD) for continuous variables. The DerSimonian–Laird random effects model was used. χ2 tests were used to study heterogeneity between trials. From the database searches, 17 relevant studies were identified and included in this meta-analysis (Supplementary data 1). Study characteristics are shown in Table 1 and baseline characteristics are shown in Table 2. Of the 17 studies, 11 were retrospective observational, 5 prospective observational and there was one randomised control trial. There were 2714 patients on dabigatran and 4436 patients on warfarin that underwent catheter ablation for AF. The dabigatran cohort was older, had a greater proportion of males and more patients with paroxysmal AF compared to the warfarin cohort. However the dabigatran cohort had a lower proportion of patients with hypertension, diabetes mellitus (DM), prior strokes and a lower CHADs2 score. There was no significant difference in aspirin use or procedure time between the two groups. Fig. 1 shows no significant difference in strokes (P = 0.82), TIA (P = 0.21) or thromboembolic events (P = 0.66). Fig. 2 highlights the complications associated with RCAF amongst the two cohorts. There was no significant difference in terms of major bleeding (P = 0.48), minor bleeding (P = 0.12), pericardial tamponade (P = 0.91) and groyne haematoma (P = 0.43) between dabigatran and warfarin administration. There is a higher risk of thromboembolism immediately after RCAF to treat AF [5]. It has been postulated that the endothelial lesion caused by the radiofrequency energy plays a significant role in activating the clotting cascade via endothelial disruption, electroporation injury and heating of circulating blood elements. In addition the mechanical trauma due to the cardioversion or the restored contractility post ablation may dislodge left atrial microthrombi [6]. The traditional anticoagulant used to minimise this risk is warfarin, which may or may not be interrupted for the procedure. However warfarin requires extensive monitoring to maintain an international normalised ratio of 2–3 to avoid increased risks of bleeding and strokes [3]. The novel anticoagulant dabigatran has less drug interactions than warfarin and requiring less monitoring. Current data appears to suggest that dabigatran has a similar efficacy profile compared to warfarin [7].
200
K. Phan et al. / International Journal of Cardiology 189 (2015) 199–203
Table 1 Study characteristics. n, number of patients; ACT, activated clotting time; R, retrospective; P, prospective; OS, observational study; RCT, randomised controlled trial. First author Year
Timing of first held dose of dabigatran
Time interval for restarting after procedure
Time first held Time restart for warfarin warfarin
150 mg twice daily 150 mg twice daily
36 or 48 h prior
Morning after
5 days prior
24–30 h prior
4–6 h
150 mg twice daily
24–36 h prior
4–6 h
Study n n Dabigatran design (dabigatran) (warfarin) dosage
Winkle
2014 R, OS
426
113
Somani
2014 R, OS
43
164
Providencia 2014 P, OS
176
192
Arshad
2014 R, OS
374
508
Yamaji
2013 R, OS
106
397
Nin
2013 P, RCT
45
Maddox
2013 R, OS
Kim
Target ACT (s)
Evening of 225 procedure Uninterrupted Uninterrupted 250–300 (cts), 300–350 uninterrupted 5 days prior Evening of N300 procedure
3 months
12
300–400
months NR
300–350
3 months
Evening of procedure 3h
45
110 mg twice daily
Morning after procedure
4h
2 weeks
212
251
Uninterrupted
2013 R, OS
191
572
Kaiser
2013 R, OS
122
135
150 mg twice daily 150 mg twice daily 150 mg twice daily
Imamura
2013 P, OS
101
126
Ichiki
2013 P, OS
30
180
Haines
2013 R, OS
202
202
150 mg twice daily
Bassioury
2013 P, OS
376
623
150 mg twice daily
Snipelisky
2012 R, OS
31
125
150 mg twice daily
Lakkireddy
2012 P, OS
145
145
150 mg twice daily
Kondura
2012 R, OS
24
52
Kaseno
2012 R, OS
110
101
110 mg twice daily
Evening of procedure Uninterrupted Day after or interrupted procedure
NR
150 mg twice 12–48 h prior daily 110 mg or 150 Morning day of mg twice daily procedure
220/300 mg twice daily NR
5 days prior
Follow-up duration
4h 300–400 Morning before procedure Uninterrupted Uninterrupted Uninterrupted N350–400
Night before procedure 3–5 days prior
4h
Uninterrupted Uninterrupted 300–350
Hospital discharge 3 months
4h
Uninterrupted Uninterrupted 300–350
≥3
12–24 h prior
3h
3 days prior
months 1 month
Morning of procedure Varies from b12 h to N48 h
NR
Uninterrupted Uninterrupted NR
NR
Varies from b6 h to N24 h
Varies from b12 h to N48
Hospital discharge
Morning of procedure or night before Morning of procedure
After arousal from sedation
Morning of procedure Uninterrupted
3h
Evening of procedure
Evening of procedure Morning after procedure
Morning of procedure
However this may be due to a lack of statistical power from the available data. In addition, there is no known reversal agent for dabigatran although there has been growing research into non-specific reversal agents [8]. Overall, the current literature appears to suggest great potential for regular dabigatran use in RCAF and further research should
3h
Day of procedure
300–350
300–350
h Uninterrupted Uninterrupted 350–450
1 month
Evening of N350 Evening procedure before procedure Uninterrupted Uninterrupted 300–350
1 month
Uninterrupted Uninterrupted N350
NR
Uninterrupted Uninterrupted 300–350
≥2
1 week
months
assess long term safety and the effects of different dosages and protocols. The current review has several limitations. This includes the heterogeneity in dosing and protocols regarding with-holding and reusing the anticoagulant, the differences in activated clotting
Table 2 Baseline characteristics. n, no of patients; N, total pooled number of patients; WM, weighted mean; RR, relative risk; WMD, weighted mean difference; AF, atrial fibrillation; CHF, congestive heart failure; HT, hypertension; DM, diabetes mellitus; TIA, transient ischemic attack; CAD, coronary artery disease; LVEF, left ventricular ejection fraction. Baseline
n/N (%) dabigatran or WM
n/N (%) warfarin or WM
RR or WMD (95% CI)
I2 (%)
P-value
Age (years) Male Non-paroxysmal AF Paroxysmal AF Persistent AF CHADS-VAsc CHADS2 CHF HT DM Prior stroke/TIA CAD LVEF (%) Aspirin (%) Procedure time (min)
60.1 1973/2714 (72.7) 690/1130 (61.1) 969/1858 (52.2) 714/1631 (43.8) 1.67 1.0 184/1772 (10.4) 1252/2428 (51.6) 219/2002 (10.9) 133/2203 (6.0) 259/1789 (14.5) 57.9 415/1408 (29.5) 185.9
61.8 3106/4436 (70.0) 1606/2578 (62.3) 1093/2662 (41.1) 1249/2632 (47.5) 1.72 1.1 293/2428 (12.1) 2218/3921 (56.6) 438/2779 (15.8) 224/2966 (7.5) 540/3422 (15.8) 57.5 549/1995 (27.5) 187.6
−1.88 (−2.91, −0.86) 1.04 (1.01, 1.08) 0.99 (0.87, 1.13) 1.14 (1.03, 1.27) 0.85 (0.70, 1.04) −0.07 (−0.35, 0.20) −0.17 (−0.30, −0.03) 0.78 (0.54, 1.13) 0.87 (0.78, 0.99) 0.67 (0.56, 0.80) 0.79 (0.62, 1.00) 0.84 (0.70, 1.01) 0.54 (−0.04, 1.13) 1.07 (0.85, 1.35) −1.96 (−7.60, 3.69)
67 0 70 67 78 86 71 72 81 19 9 33 39 74 62
0.0003 0.004 0.87 0.02 0.11 0.60 0.01 0.19 0.03 b0.0001 0.05 0.07 0.07 0.56 0.50
K. Phan et al. / International Journal of Cardiology 189 (2015) 199–203
201
Fig. 1. Forest plots comparing dabigatran versus warfarin in catheter ablation in terms of (A) strokes; (B) TIA; (C) thromboembolism.
factor times, the lack of patient level data which prevents covariate and subgroup analysis, differences between centres in terms of operator experience, instrumentation, energy of ablation used and antiarrhythmic drug protocols. The analysis also includes
observational non-randomised studies and thus the results may be susceptible to selection bias. Furthermore, the majority of studies presented only short-term follow-up data, which may undermine the validity of the presented data [9]. Future prospective, multi-
202
K. Phan et al. / International Journal of Cardiology 189 (2015) 199–203
Fig. 2. Forest plots comparing dabigatran versus warfarin for catheter ablation in terms of (A) major bleeding; (B) minor bleeding; (C) pericardial tamponade; and (D) groyne hematoma.
centre studies should be designed to further address these clinical questions. In general, there was incomplete reporting of outcomes across all studies.
In conclusion, the meta-analysis suggests that dabigatran and warfarin have similar safety and efficacy for periprocedural anticoagulation for AF catheter ablation in carefully selected patients. These trends
K. Phan et al. / International Journal of Cardiology 189 (2015) 199–203
should be further validated in randomised trials and large prospective, multicentre registries. Supplementary data to this article can be found online at http://dx. doi.org/10.1016/j.ijcard.2015.04.072. Conflict of interest None declared. Funding None declared. Acknowledgements None declared. References [1] T. Crawford, H. Oral, Current status and outcomes of catheter ablation for atrial fibrillation, Heart Rhythm. 6 (2009) S12–S17. [2] K. Kearney, R. Stephenson, K. Phan, W.Y. Chan, M.Y. Huang, T.D. Yan, A systematic review of surgical ablation versus catheter ablation for trial fibrillation, Ann. Cardiothorac. Surg. 3 (2014) 15–29.
203
[3] P. Santangeli, L. Di Biase, R. Horton, J.D. Burkhardt, J. Sanchez, A. Al- Ahmad, R. Hongo, S. Beheiry, R. Bai, P. Mohanty, W.R. Lewis, A. Natale, Ablation of atrial fibrillation under therapeutic warfarin reduces periprocedural complications: evidence from a meta-analysis, Circ. Arrhythm. Electrophysiol. 5 (2012) 302–311. [4] C. Eitel, J. Koch, P. Sommer, S. John, S. Kircher, A. Bollmann, A. Arya, C. Piorkowski, G. Hindricks, Novel oral anticoagulants in a real-world cohort of patients undergoing catheter ablation of atrial fibrillation, Europace 15 (2013) 1587–1593. [5] S. Themistoclakis, A. Corrado, F.E. Marchlinski, P. Jais, E. Zado, A. Rossillo, et al., The risk of thromboembolism and need for oral anticoagulation after successful atrial fibrillation ablation, J. Am. Coll. Cardiol. 55 (8) (2010) 735–743. [6] Fiorenzo Gaita, Domenico Caponi, Martina Pianelli, Marco Scaglione, Elisabetta Toso, Federico Cesarani, Carlo Boffano, et al., Radiofrequency catheter ablation of atrial fibrillation: a cause of silent thromboembolism? Magnetic resonance imaging assessment of cerebral thromboembolism in patients undergoing ablation of atrial fibrillation, Circulation 122 (17) (2010) 1667–1673. [7] R. Providência, J.-P. Albenque, S. Combes, A. Bouzeman, B. Casteigt, N. Combes, K. Narayanan, E. Marijon, S. Boveda, Safety and efficacy of dabigatran versus warfarin in patients undergoing catheter ablation of atrial fibrillation: a systematic review and meta-analysis, Heart 100 (2014) 324–335. [8] Raphael Marlu, et al., Effect of non-specific reversal agents on anticoagulant activity of dabigatran and rivaroxaban, Thromb. Haemost. 108 (2) (2012) 217–224. [9] K. Phan, D.H. Tian, C. Cao, D. Black, T.D. Yan, Systematic review and meta-analysis: techniques and a guide for the academic surgeon, Ann. Cardiothorac. Surg. 4 (5) (2015) 112–122.
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Letter to the Editor
Meta-analysis of dabigatran vs warfarin in patients undergoing catheter ablation for atrial fibrillation Kevin Phan a,b,⁎, Nelson Wang b, Laurent Pison c, Narendra Kumar c, Kerry Hitos b,d, Stuart P. Thomas a,b a
Department of Cardiology, Westmead Hospital, Sydney, Australia University of Sydney, Sydney, Australia Department of Cardiology, Maastricht University Hospital, Maastricht, The Netherlands d Department of Surgery, Westmead Hospital, Sydney, Australia b c
a r t i c l e
i n f o
Article history: Received 24 January 2015 Received in revised form 25 March 2015 Accepted 9 April 2015 Available online 11 April 2015 Keywords: Catheter ablation Dabigatran Warfarin Thromboembolism VKA Systematic review
Radiofrequency catheter ablation (RFCA) is increasingly used for to treat symptomatic atrial fibrillation (AF), particularly after failure of medical therapy [1,2]. However there is substantial risk of thromboembolism perioperatively. Warfarin has traditionally been used as the anticoagulant of choice despite the significant monitoring required and the long duration of onset [3]. New oral anticoagulants (NOACs) such as apixaban, dabigatran, and rivaroxaban have been introduced as alternatives to warfarin, and act via direct inhibition of thrombin or factor Xa [4]. The current study sought to analyse the efficacy and safety of dabigatran as an anticoagulant in RFCA compared to warfarin in the setting of catheter ablation procedures. Electronic searches were performed using six electronic databases, using the terms “dabigatran”, “warfarin”, “VKA”, “ablation” and “atrial fibrillation” as keywords or MeSH headings. We included studies comparing dabigatran and warfarin for patients undergoing catheter ablation, with at least 10 patients in each cohort. When institutions published duplicate studies with accumulating numbers of patients or increased lengths of follow-up, only the most complete reports were
⁎ Corresponding author at: Department of Cardiology, Westmead Hospital, Hawkesbury Rd, Westmead, Sydney, NSW 2145, Australia. E-mail address: [email protected] (K. Phan).
http://dx.doi.org/10.1016/j.ijcard.2015.04.072 0167-5273/© 2015 Elsevier Ireland Ltd. All rights reserved.
included for quantitative assessment at each time interval. Abstracts, case reports, conference presentations, editorials, and expert opinions were excluded. Meta-analysis was performed by combining extracted data as pooled incidence of mortality or complications. The relative risk (RR) was used as a summary statistic for dichotomous variables, and weighted mean difference (WMD) for continuous variables. The DerSimonian–Laird random effects model was used. χ2 tests were used to study heterogeneity between trials. From the database searches, 17 relevant studies were identified and included in this meta-analysis (Supplementary data 1). Study characteristics are shown in Table 1 and baseline characteristics are shown in Table 2. Of the 17 studies, 11 were retrospective observational, 5 prospective observational and there was one randomised control trial. There were 2714 patients on dabigatran and 4436 patients on warfarin that underwent catheter ablation for AF. The dabigatran cohort was older, had a greater proportion of males and more patients with paroxysmal AF compared to the warfarin cohort. However the dabigatran cohort had a lower proportion of patients with hypertension, diabetes mellitus (DM), prior strokes and a lower CHADs2 score. There was no significant difference in aspirin use or procedure time between the two groups. Fig. 1 shows no significant difference in strokes (P = 0.82), TIA (P = 0.21) or thromboembolic events (P = 0.66). Fig. 2 highlights the complications associated with RCAF amongst the two cohorts. There was no significant difference in terms of major bleeding (P = 0.48), minor bleeding (P = 0.12), pericardial tamponade (P = 0.91) and groyne haematoma (P = 0.43) between dabigatran and warfarin administration. There is a higher risk of thromboembolism immediately after RCAF to treat AF [5]. It has been postulated that the endothelial lesion caused by the radiofrequency energy plays a significant role in activating the clotting cascade via endothelial disruption, electroporation injury and heating of circulating blood elements. In addition the mechanical trauma due to the cardioversion or the restored contractility post ablation may dislodge left atrial microthrombi [6]. The traditional anticoagulant used to minimise this risk is warfarin, which may or may not be interrupted for the procedure. However warfarin requires extensive monitoring to maintain an international normalised ratio of 2–3 to avoid increased risks of bleeding and strokes [3]. The novel anticoagulant dabigatran has less drug interactions than warfarin and requiring less monitoring. Current data appears to suggest that dabigatran has a similar efficacy profile compared to warfarin [7].
200
K. Phan et al. / International Journal of Cardiology 189 (2015) 199–203
Table 1 Study characteristics. n, number of patients; ACT, activated clotting time; R, retrospective; P, prospective; OS, observational study; RCT, randomised controlled trial. First author Year
Timing of first held dose of dabigatran
Time interval for restarting after procedure
Time first held Time restart for warfarin warfarin
150 mg twice daily 150 mg twice daily
36 or 48 h prior
Morning after
5 days prior
24–30 h prior
4–6 h
150 mg twice daily
24–36 h prior
4–6 h
Study n n Dabigatran design (dabigatran) (warfarin) dosage
Winkle
2014 R, OS
426
113
Somani
2014 R, OS
43
164
Providencia 2014 P, OS
176
192
Arshad
2014 R, OS
374
508
Yamaji
2013 R, OS
106
397
Nin
2013 P, RCT
45
Maddox
2013 R, OS
Kim
Target ACT (s)
Evening of 225 procedure Uninterrupted Uninterrupted 250–300 (cts), 300–350 uninterrupted 5 days prior Evening of N300 procedure
3 months
12
300–400
months NR
300–350
3 months
Evening of procedure 3h
45
110 mg twice daily
Morning after procedure
4h
2 weeks
212
251
Uninterrupted
2013 R, OS
191
572
Kaiser
2013 R, OS
122
135
150 mg twice daily 150 mg twice daily 150 mg twice daily
Imamura
2013 P, OS
101
126
Ichiki
2013 P, OS
30
180
Haines
2013 R, OS
202
202
150 mg twice daily
Bassioury
2013 P, OS
376
623
150 mg twice daily
Snipelisky
2012 R, OS
31
125
150 mg twice daily
Lakkireddy
2012 P, OS
145
145
150 mg twice daily
Kondura
2012 R, OS
24
52
Kaseno
2012 R, OS
110
101
110 mg twice daily
Evening of procedure Uninterrupted Day after or interrupted procedure
NR
150 mg twice 12–48 h prior daily 110 mg or 150 Morning day of mg twice daily procedure
220/300 mg twice daily NR
5 days prior
Follow-up duration
4h 300–400 Morning before procedure Uninterrupted Uninterrupted Uninterrupted N350–400
Night before procedure 3–5 days prior
4h
Uninterrupted Uninterrupted 300–350
Hospital discharge 3 months
4h
Uninterrupted Uninterrupted 300–350
≥3
12–24 h prior
3h
3 days prior
months 1 month
Morning of procedure Varies from b12 h to N48 h
NR
Uninterrupted Uninterrupted NR
NR
Varies from b6 h to N24 h
Varies from b12 h to N48
Hospital discharge
Morning of procedure or night before Morning of procedure
After arousal from sedation
Morning of procedure Uninterrupted
3h
Evening of procedure
Evening of procedure Morning after procedure
Morning of procedure
However this may be due to a lack of statistical power from the available data. In addition, there is no known reversal agent for dabigatran although there has been growing research into non-specific reversal agents [8]. Overall, the current literature appears to suggest great potential for regular dabigatran use in RCAF and further research should
3h
Day of procedure
300–350
300–350
h Uninterrupted Uninterrupted 350–450
1 month
Evening of N350 Evening procedure before procedure Uninterrupted Uninterrupted 300–350
1 month
Uninterrupted Uninterrupted N350
NR
Uninterrupted Uninterrupted 300–350
≥2
1 week
months
assess long term safety and the effects of different dosages and protocols. The current review has several limitations. This includes the heterogeneity in dosing and protocols regarding with-holding and reusing the anticoagulant, the differences in activated clotting
Table 2 Baseline characteristics. n, no of patients; N, total pooled number of patients; WM, weighted mean; RR, relative risk; WMD, weighted mean difference; AF, atrial fibrillation; CHF, congestive heart failure; HT, hypertension; DM, diabetes mellitus; TIA, transient ischemic attack; CAD, coronary artery disease; LVEF, left ventricular ejection fraction. Baseline
n/N (%) dabigatran or WM
n/N (%) warfarin or WM
RR or WMD (95% CI)
I2 (%)
P-value
Age (years) Male Non-paroxysmal AF Paroxysmal AF Persistent AF CHADS-VAsc CHADS2 CHF HT DM Prior stroke/TIA CAD LVEF (%) Aspirin (%) Procedure time (min)
60.1 1973/2714 (72.7) 690/1130 (61.1) 969/1858 (52.2) 714/1631 (43.8) 1.67 1.0 184/1772 (10.4) 1252/2428 (51.6) 219/2002 (10.9) 133/2203 (6.0) 259/1789 (14.5) 57.9 415/1408 (29.5) 185.9
61.8 3106/4436 (70.0) 1606/2578 (62.3) 1093/2662 (41.1) 1249/2632 (47.5) 1.72 1.1 293/2428 (12.1) 2218/3921 (56.6) 438/2779 (15.8) 224/2966 (7.5) 540/3422 (15.8) 57.5 549/1995 (27.5) 187.6
−1.88 (−2.91, −0.86) 1.04 (1.01, 1.08) 0.99 (0.87, 1.13) 1.14 (1.03, 1.27) 0.85 (0.70, 1.04) −0.07 (−0.35, 0.20) −0.17 (−0.30, −0.03) 0.78 (0.54, 1.13) 0.87 (0.78, 0.99) 0.67 (0.56, 0.80) 0.79 (0.62, 1.00) 0.84 (0.70, 1.01) 0.54 (−0.04, 1.13) 1.07 (0.85, 1.35) −1.96 (−7.60, 3.69)
67 0 70 67 78 86 71 72 81 19 9 33 39 74 62
0.0003 0.004 0.87 0.02 0.11 0.60 0.01 0.19 0.03 b0.0001 0.05 0.07 0.07 0.56 0.50
K. Phan et al. / International Journal of Cardiology 189 (2015) 199–203
201
Fig. 1. Forest plots comparing dabigatran versus warfarin in catheter ablation in terms of (A) strokes; (B) TIA; (C) thromboembolism.
factor times, the lack of patient level data which prevents covariate and subgroup analysis, differences between centres in terms of operator experience, instrumentation, energy of ablation used and antiarrhythmic drug protocols. The analysis also includes
observational non-randomised studies and thus the results may be susceptible to selection bias. Furthermore, the majority of studies presented only short-term follow-up data, which may undermine the validity of the presented data [9]. Future prospective, multi-
202
K. Phan et al. / International Journal of Cardiology 189 (2015) 199–203
Fig. 2. Forest plots comparing dabigatran versus warfarin for catheter ablation in terms of (A) major bleeding; (B) minor bleeding; (C) pericardial tamponade; and (D) groyne hematoma.
centre studies should be designed to further address these clinical questions. In general, there was incomplete reporting of outcomes across all studies.
In conclusion, the meta-analysis suggests that dabigatran and warfarin have similar safety and efficacy for periprocedural anticoagulation for AF catheter ablation in carefully selected patients. These trends
K. Phan et al. / International Journal of Cardiology 189 (2015) 199–203
should be further validated in randomised trials and large prospective, multicentre registries. Supplementary data to this article can be found online at http://dx. doi.org/10.1016/j.ijcard.2015.04.072. Conflict of interest None declared. Funding None declared. Acknowledgements None declared. References [1] T. Crawford, H. Oral, Current status and outcomes of catheter ablation for atrial fibrillation, Heart Rhythm. 6 (2009) S12–S17. [2] K. Kearney, R. Stephenson, K. Phan, W.Y. Chan, M.Y. Huang, T.D. Yan, A systematic review of surgical ablation versus catheter ablation for trial fibrillation, Ann. Cardiothorac. Surg. 3 (2014) 15–29.
203
[3] P. Santangeli, L. Di Biase, R. Horton, J.D. Burkhardt, J. Sanchez, A. Al- Ahmad, R. Hongo, S. Beheiry, R. Bai, P. Mohanty, W.R. Lewis, A. Natale, Ablation of atrial fibrillation under therapeutic warfarin reduces periprocedural complications: evidence from a meta-analysis, Circ. Arrhythm. Electrophysiol. 5 (2012) 302–311. [4] C. Eitel, J. Koch, P. Sommer, S. John, S. Kircher, A. Bollmann, A. Arya, C. Piorkowski, G. Hindricks, Novel oral anticoagulants in a real-world cohort of patients undergoing catheter ablation of atrial fibrillation, Europace 15 (2013) 1587–1593. [5] S. Themistoclakis, A. Corrado, F.E. Marchlinski, P. Jais, E. Zado, A. Rossillo, et al., The risk of thromboembolism and need for oral anticoagulation after successful atrial fibrillation ablation, J. Am. Coll. Cardiol. 55 (8) (2010) 735–743. [6] Fiorenzo Gaita, Domenico Caponi, Martina Pianelli, Marco Scaglione, Elisabetta Toso, Federico Cesarani, Carlo Boffano, et al., Radiofrequency catheter ablation of atrial fibrillation: a cause of silent thromboembolism? Magnetic resonance imaging assessment of cerebral thromboembolism in patients undergoing ablation of atrial fibrillation, Circulation 122 (17) (2010) 1667–1673. [7] R. Providência, J.-P. Albenque, S. Combes, A. Bouzeman, B. Casteigt, N. Combes, K. Narayanan, E. Marijon, S. Boveda, Safety and efficacy of dabigatran versus warfarin in patients undergoing catheter ablation of atrial fibrillation: a systematic review and meta-analysis, Heart 100 (2014) 324–335. [8] Raphael Marlu, et al., Effect of non-specific reversal agents on anticoagulant activity of dabigatran and rivaroxaban, Thromb. Haemost. 108 (2) (2012) 217–224. [9] K. Phan, D.H. Tian, C. Cao, D. Black, T.D. Yan, Systematic review and meta-analysis: techniques and a guide for the academic surgeon, Ann. Cardiothorac. Surg. 4 (5) (2015) 112–122.