- Email: [email protected]
Anticoagulation for Cardioversion of Acute Onset Atrial Fibrillation
JACC: CLINICAL ELECTROPHYSIOLOGY
VOL.
ª 2016 BY THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION
-, NO. -, 2016
ISSN 2405-500X/$36.00
PUBLISHED BY ELSEVIER
http://dx.doi.org/10.1016/j.jacep.2016.03.002
EDITORIAL COMMENT
Anticoagulation for Cardioversion of Acute Onset Atrial Fibrillation Time to Revise Guidelines?* Demosthenes G. Katritsis, MD, PHD, Mark E. Josephson, MD
UFELEEIN H MH BLAP TEIN (First do no harm)
T
Hippocrates (1) he need of proper anticoagulation for cardioversion of atrial fibrillation (AF) episodes with duration $48 h is well established.
Nonanticoagulated patients carry a risk for thromboembolism of up to 10% (2), whereas the risk in
anticoagulated patients depends on the intensity of anticoagulation, with reported values ranging from 0% to 4% (2–4). The optimum management of patients
who
undergo
cardioversion
performed
within 48 h after AF onset has been controversial. The 2010 European Society of Cardiology guidelines recommend intravenous heparin or weight adjusted therapeutic dose low molecular weight heparin pericardioversion,
without
the
need
for
post-
cardioversion oral anticoagulation, in the absence of thromboembolic risk factors (IIb-C) (5). The 2012 update of the ESC guidelines, although they refer to peri-cardioversion anticoagulation, do not provide specific recommendations on the issue (6). The American Heart Association/American College of Cardiology/Heart Rhythm Society 2014 guidelines allow, on a Class IIB-C recommendation, even no antithrombotic for cardioversion at all in patients at low thromboembolic risk (7). The choice of Class IIb-C recommendation by both American and European guidelines, is indicative of the limited, and controversial,
data
on
the
issue
when
these
recommendations appeared. However, we now have substantially more information to guide us on an evidence-based management of these patients. Although some earlier studies had not detected thromboembolism following cardioversion of acute AF
(<48
h
duration)
performed
without
anti-
coagulation (8–11), there had been evidence that the likelihood of thromboembolism following cardioversion of AF lasting <48 h is not negligible, approximately 0.7% to 0.8% (12,13). In the more recent FinCV (Finnish CardioVersion) study on 5,116 cardioversions performed for AF lasting <48 h without peri- or postprocedural anticoagulation, embolic events were documented in 38 patients. Of note, 26% of them had CHA2DS 2VASc score 0 to 1 (13). In this issue of JACC: Clinical Electrophysiology, Garg et al. (14) provide further useful information on a retrospective analysis of 567 cardioversions, performed in 484 patients within 48 h since the onset of AF and without therapeutic anticoagulation. Patients had a 5 times higher chance to get a thromboembolic event compared to those properly anticoagulated. However, no events were documented in post-operative patients, and in those with CHA2DS 2VASc score <2. Further information can be gained by a careful look at the actual data presented by Garg et al. (14). First, in 6.7% of patients with a CHA 2DS2VASc score 0, smoke was identified by the transesophageal echocardiography (TEE), thus indicating the potential thrombogenicity of the procedure regardless of underlying risk factors. Second, thromboembolism did not always occur immediately after cardioversion due to thrombus dislodgement.
*Editorials published in JACC: Clinical Electrophysiology reflect the views of the authors and do not necessarily represent the views of JACC: Clinical Electrophysiology or the American College of Cardiology. From the Beth Israel Deaconess Medical Center, Harvard Medical School,
Third, although at Cleveland Clinic patients who were chosen for anticoagulation had a higher percentage of comorbidities such as prior stroke and heart failure,
Boston, Massachusetts. Both authors have reported that they have no
these comorbidities were not entirely absent in
relationships relevant to the contents of this paper to disclose.
the non-anticoagulated group (14). However, prior
2
Katritsis and Josephson
JACC: CLINICAL ELECTROPHYSIOLOGY VOL.
-, NO. -, 2016 -, 2016:-–-
Anticoagulation for Cardioversion of Acute Onset Atrial Fibrillation
stroke/transient ischemic attack is the most powerful
issue are limited, should be used. Post-cardioversion,
risk factor for thromboembolism in AF, and reliably
if the AF is nonvalvular, non–vitamin K-dependent
confers a stroke risk averaging 10% per year (15). In
anticoagulant agents are preferable to warfarin, as
the large Danish registry on 16,274 patients subjected
the 3 major trials suggested (18–21), and the X-Vert
to cardioversion of AF of undetermined duration,
(eXplore the efficacy and safety of once-daily oral
thromboembolic risk stratification by the CHA 2DS2-
riVaroxaban for the prevention of caRdiovascular
VASc score did not change the results, and even
events in patients with non-valvular aTrial fibrilla-
patients with scores 0 to 1 had a doubled risk of
tion scheduled for cardioversion) trial indicated (22).
thromboembolism following cardioversion without,
Of course, all patients should be considered on an
as opposed to, anticoagulation (2).
individual basis, and in view of the CHA2DS2VASc
These data indicate that patients with acute
score, as well as risk factors for both thromboem-
(<48 h) AF, and even with a CHA 2DS 2VASc score <2,
bolism
should not be cardioverted, either with drugs or DC,
CHA 2DS2VASc score, such as 65 to 74 years of age,
without anticoagulation. We think that both peri- and
renal and liver function, and drugs and alcohol
and
bleeding
not
considered
by
the
post-cardioversion anticoagulation for 1 month, as
abuse. In general, however, cardioversion with
thromboembolism may occur well beyond cardio-
intravenous unfractionated heparin and followed by
version, should be given a IIa-(B-NR) or at least a
1-month treatment with therapeutic warfarin, or a
IIa-(C-LD) recommendation. This recommendation is
non–vitamin K-dependent anticoagulant agent for
even stronger regarding patients not subjected to
nonvalvular AF, appears to be the most prudent and
TEE. A TEE, in cases of no prior adequate anti-
safe approach, especially in patients >65 years of
coagulation, is advisable regardless of the AF episode
age. Cardioversion-related thromboembolism is an
duration, since in AF lasting <48 h left atrial thrombi
iatrogenic complication, and we must do our utmost
have been detected in 1.4% of patients, and dense
to protect our patients from such a devastating
spontaneous echo contrast in 10%, of whom 63%
event.
were receiving anticoagulant therapy (16). Previous asymptomatic episodes cannot be excluded, and
REPRINT REQUESTS AND CORRESPONDENCE: Dr.
subclinical episodes of AF are associated with
Demosthenes G. Katritsis, Division of Cardiology,
silent cerebral infarcts (17). For pericardioversion
Beth Israel Deaconess Medical Center, 185 Pilgrim
anticoagulation, unfractionated heparin, or even a
Road, Baker 4, Boston, Massachusetts 02215. E-mail:
low molecular weight heparin, although data on this
[email protected].
REFERENCES 1. Hippocrates. Hippocrates quotes. Available at: https://www.goodreads.com/author/quotes/ 248774.Hippocrates. Accessed March 23, 2016. 2. Hansen ML, Jepsen RM, Olesen JB, et al. Thromboembolic risk in 16 274 atrial fibrillation patients undergoing direct current cardioversion with and without oral anticoagulant therapy. Europace 2015;17:18–23. 3. Klein AL, Grimm RA, Murray RD, et al., Assessment of Cardioversion Using Transesophageal Echocardiography Investigators. Use of transesophageal echocardiography to guide cardioversion in patients with atrial fibrillation. N Engl J Med 2001;344:1411–20. 4. Gallagher MM, Hennessy BJ, Edvardsson N, et al. Embolic complications of direct current cardioversion of atrial arrhythmias: association with low intensity of anticoagulation at the time of cardioversion. J Am Coll Cardiol 2002;40:926–33.
6. Camm AJ, Lip GY, De Caterina R, et al., ESC Committee for Practice Guidelines-CPG. 2012 focused update of the ESC Guidelines for the
10. Stiell IG, Clement CM, Perry JJ, et al. Association of the Ottawa Aggressive Protocol with rapid discharge of emergency department patients with
management of atrial fibrillation: an update of the 2010 ESC Guidelines for the management of atrial fibrillation–developed with the special contribution of the European Heart Rhythm Association. Europace 2012;14:1385–413.
recent-onset atrial fibrillation or flutter. CJEM 2010;12:181–91.
7. January CT, Wann LS, Alpert JS, et al. 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol 2014; 64:e1–76. 8. Burton JH, Vinson DR, Drummond K, Strout TD, Thode HC, McInturff JJ. Electrical cardioversion of emergency department patients with atrial fibrillation. Ann Emerg Med 2004;44:20–30.
5. European Heart Rhythm Association, European Association for Cardio-Thoracic Surgery, Camm AJ, et al. Guidelines for the management of atrial
9. Xavier Scheuermeyer F, Grafstein E, Stenstrom R, Innes G, Poureslami I, Sighary M. Thirty-day outcomes of emergency department
fibrillation: the Task Force for the Management of Atrial Fibrillation of the European Society of Cardiology (ESC). Eur Heart J 2010;31:2369–429.
patients undergoing electrical cardioversion for atrial fibrillation or flutter. Acad Emerg Med 2010; 17:408–15.
11. Michael JA, Stiell IG, Agarwal S, Mandavia DP. Cardioversion of paroxysmal atrial fibrillation in the emergency department. Ann Emerg Med 1999;33:379–87. 12. Weigner MJ, Caulfield TA, Danias PG, Silverman DI, Manning WJ. Risk for clinical thromboembolism associated with conversion to sinus rhythm in patients with atrial fibrillation lasting less than 48 hours. Ann Intern Med 1997; 126:615–20. 13. Airaksinen KE, Grönberg T, Nuotio I, et al. Thromboembolic complications after cardioversion of acute atrial fibrillation: the FinCV (Finnish CardioVersion) study. J Am Coll Cardiol 2013;62: 1187–92. 14. Garg A, Khunger M, Seicean S, Chung M, Tchou P. Incidence of thromboembolic complications within 30 days of electrical cardioversion performed within 48 hours of atrial fibrillation onset. J Am Coll Cardiol EP 2016;2:XX.
JACC: CLINICAL ELECTROPHYSIOLOGY VOL.
-, 2016:-–-
-, NO. -, 2016
Katritsis and Josephson Anticoagulation for Cardioversion of Acute Onset Atrial Fibrillation
15. Stroke Risk in Atrial Fibrillation Working Group. Independent predictors of stroke in patients with atrial fibrillation: a systematic review. Neurology 2007;69:546–54.
18. Nagarakanti R, Ezekowitz MD, Oldgren J, et al. Dabigatran versus warfarin in patients with atrial fibrillation: an analysis of patients undergoing cardioversion. Circulation 2011;123:131–6.
16. Kleemann T, Becker T, Strauss M, Schneider S, Seidl K. Prevalence of left atrial thrombus and dense spontaneous echo contrast in patients with short-term atrial fibrillation <48 hours undergoing cardioversion: value of transesophageal
19. Flaker G, Lopes RD, Al-Khatib SM, et al., ARISTOTLE Committees and Investigators. Effi-
echocardiography to guide cardioversion. J Am Soc Echocardiogr 2009;22:1403–8. 17. Gaita F, Corsinovi L, Anselmino M, et al. Prevalence of silent cerebral ischemia in paroxysmal and persistent atrial fibrillation and correlation with cognitive function. J Am Coll Cardiol 2013;62:1990–7.
cacy and safety of apixaban in patients after cardioversion for atrial fibrillation: insights from the ARISTOTLE Trial (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation). J Am Coll Cardiol 2014;63: 1082–7. 20. Piccini JP, Stevens SR, Lokhnygina Y, et al., ROCKET AF Steering Committee & Investigators. Outcomes after cardioversion and atrial fibrillation
ablation in patients treated with rivaroxaban and warfarin in the ROCKET AF trial. J Am Coll Cardiol 2013;61:1998–2006. 21. Katritsis DG, Gersh BJ, Camm AJ. Anticoagulation in atrial fibrillation. Current concepts. Arrhythm Electrophysiol Rev 2015;4:100–7. 22. Cappato R, Ezekowitz MD, Klein AL, et al., on behalf of the X-VeRT Investigators. Rivaroxaban vs. vitamin K antagonists for cardioversion in atrial fibrillation. Eur Heart J 2014;35: 3346–55.
KEY WORDS anticoagulation, atrial fibrillation, cardioversion
3
VOL.
ª 2016 BY THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION
-, NO. -, 2016
ISSN 2405-500X/$36.00
PUBLISHED BY ELSEVIER
http://dx.doi.org/10.1016/j.jacep.2016.03.002
EDITORIAL COMMENT
Anticoagulation for Cardioversion of Acute Onset Atrial Fibrillation Time to Revise Guidelines?* Demosthenes G. Katritsis, MD, PHD, Mark E. Josephson, MD
UFELEEIN H MH BLAP TEIN (First do no harm)
T
Hippocrates (1) he need of proper anticoagulation for cardioversion of atrial fibrillation (AF) episodes with duration $48 h is well established.
Nonanticoagulated patients carry a risk for thromboembolism of up to 10% (2), whereas the risk in
anticoagulated patients depends on the intensity of anticoagulation, with reported values ranging from 0% to 4% (2–4). The optimum management of patients
who
undergo
cardioversion
performed
within 48 h after AF onset has been controversial. The 2010 European Society of Cardiology guidelines recommend intravenous heparin or weight adjusted therapeutic dose low molecular weight heparin pericardioversion,
without
the
need
for
post-
cardioversion oral anticoagulation, in the absence of thromboembolic risk factors (IIb-C) (5). The 2012 update of the ESC guidelines, although they refer to peri-cardioversion anticoagulation, do not provide specific recommendations on the issue (6). The American Heart Association/American College of Cardiology/Heart Rhythm Society 2014 guidelines allow, on a Class IIB-C recommendation, even no antithrombotic for cardioversion at all in patients at low thromboembolic risk (7). The choice of Class IIb-C recommendation by both American and European guidelines, is indicative of the limited, and controversial,
data
on
the
issue
when
these
recommendations appeared. However, we now have substantially more information to guide us on an evidence-based management of these patients. Although some earlier studies had not detected thromboembolism following cardioversion of acute AF
(<48
h
duration)
performed
without
anti-
coagulation (8–11), there had been evidence that the likelihood of thromboembolism following cardioversion of AF lasting <48 h is not negligible, approximately 0.7% to 0.8% (12,13). In the more recent FinCV (Finnish CardioVersion) study on 5,116 cardioversions performed for AF lasting <48 h without peri- or postprocedural anticoagulation, embolic events were documented in 38 patients. Of note, 26% of them had CHA2DS 2VASc score 0 to 1 (13). In this issue of JACC: Clinical Electrophysiology, Garg et al. (14) provide further useful information on a retrospective analysis of 567 cardioversions, performed in 484 patients within 48 h since the onset of AF and without therapeutic anticoagulation. Patients had a 5 times higher chance to get a thromboembolic event compared to those properly anticoagulated. However, no events were documented in post-operative patients, and in those with CHA2DS 2VASc score <2. Further information can be gained by a careful look at the actual data presented by Garg et al. (14). First, in 6.7% of patients with a CHA 2DS2VASc score 0, smoke was identified by the transesophageal echocardiography (TEE), thus indicating the potential thrombogenicity of the procedure regardless of underlying risk factors. Second, thromboembolism did not always occur immediately after cardioversion due to thrombus dislodgement.
*Editorials published in JACC: Clinical Electrophysiology reflect the views of the authors and do not necessarily represent the views of JACC: Clinical Electrophysiology or the American College of Cardiology. From the Beth Israel Deaconess Medical Center, Harvard Medical School,
Third, although at Cleveland Clinic patients who were chosen for anticoagulation had a higher percentage of comorbidities such as prior stroke and heart failure,
Boston, Massachusetts. Both authors have reported that they have no
these comorbidities were not entirely absent in
relationships relevant to the contents of this paper to disclose.
the non-anticoagulated group (14). However, prior
2
Katritsis and Josephson
JACC: CLINICAL ELECTROPHYSIOLOGY VOL.
-, NO. -, 2016 -, 2016:-–-
Anticoagulation for Cardioversion of Acute Onset Atrial Fibrillation
stroke/transient ischemic attack is the most powerful
issue are limited, should be used. Post-cardioversion,
risk factor for thromboembolism in AF, and reliably
if the AF is nonvalvular, non–vitamin K-dependent
confers a stroke risk averaging 10% per year (15). In
anticoagulant agents are preferable to warfarin, as
the large Danish registry on 16,274 patients subjected
the 3 major trials suggested (18–21), and the X-Vert
to cardioversion of AF of undetermined duration,
(eXplore the efficacy and safety of once-daily oral
thromboembolic risk stratification by the CHA 2DS2-
riVaroxaban for the prevention of caRdiovascular
VASc score did not change the results, and even
events in patients with non-valvular aTrial fibrilla-
patients with scores 0 to 1 had a doubled risk of
tion scheduled for cardioversion) trial indicated (22).
thromboembolism following cardioversion without,
Of course, all patients should be considered on an
as opposed to, anticoagulation (2).
individual basis, and in view of the CHA2DS2VASc
These data indicate that patients with acute
score, as well as risk factors for both thromboem-
(<48 h) AF, and even with a CHA 2DS 2VASc score <2,
bolism
should not be cardioverted, either with drugs or DC,
CHA 2DS2VASc score, such as 65 to 74 years of age,
without anticoagulation. We think that both peri- and
renal and liver function, and drugs and alcohol
and
bleeding
not
considered
by
the
post-cardioversion anticoagulation for 1 month, as
abuse. In general, however, cardioversion with
thromboembolism may occur well beyond cardio-
intravenous unfractionated heparin and followed by
version, should be given a IIa-(B-NR) or at least a
1-month treatment with therapeutic warfarin, or a
IIa-(C-LD) recommendation. This recommendation is
non–vitamin K-dependent anticoagulant agent for
even stronger regarding patients not subjected to
nonvalvular AF, appears to be the most prudent and
TEE. A TEE, in cases of no prior adequate anti-
safe approach, especially in patients >65 years of
coagulation, is advisable regardless of the AF episode
age. Cardioversion-related thromboembolism is an
duration, since in AF lasting <48 h left atrial thrombi
iatrogenic complication, and we must do our utmost
have been detected in 1.4% of patients, and dense
to protect our patients from such a devastating
spontaneous echo contrast in 10%, of whom 63%
event.
were receiving anticoagulant therapy (16). Previous asymptomatic episodes cannot be excluded, and
REPRINT REQUESTS AND CORRESPONDENCE: Dr.
subclinical episodes of AF are associated with
Demosthenes G. Katritsis, Division of Cardiology,
silent cerebral infarcts (17). For pericardioversion
Beth Israel Deaconess Medical Center, 185 Pilgrim
anticoagulation, unfractionated heparin, or even a
Road, Baker 4, Boston, Massachusetts 02215. E-mail:
low molecular weight heparin, although data on this
[email protected].
REFERENCES 1. Hippocrates. Hippocrates quotes. Available at: https://www.goodreads.com/author/quotes/ 248774.Hippocrates. Accessed March 23, 2016. 2. Hansen ML, Jepsen RM, Olesen JB, et al. Thromboembolic risk in 16 274 atrial fibrillation patients undergoing direct current cardioversion with and without oral anticoagulant therapy. Europace 2015;17:18–23. 3. Klein AL, Grimm RA, Murray RD, et al., Assessment of Cardioversion Using Transesophageal Echocardiography Investigators. Use of transesophageal echocardiography to guide cardioversion in patients with atrial fibrillation. N Engl J Med 2001;344:1411–20. 4. Gallagher MM, Hennessy BJ, Edvardsson N, et al. Embolic complications of direct current cardioversion of atrial arrhythmias: association with low intensity of anticoagulation at the time of cardioversion. J Am Coll Cardiol 2002;40:926–33.
6. Camm AJ, Lip GY, De Caterina R, et al., ESC Committee for Practice Guidelines-CPG. 2012 focused update of the ESC Guidelines for the
10. Stiell IG, Clement CM, Perry JJ, et al. Association of the Ottawa Aggressive Protocol with rapid discharge of emergency department patients with
management of atrial fibrillation: an update of the 2010 ESC Guidelines for the management of atrial fibrillation–developed with the special contribution of the European Heart Rhythm Association. Europace 2012;14:1385–413.
recent-onset atrial fibrillation or flutter. CJEM 2010;12:181–91.
7. January CT, Wann LS, Alpert JS, et al. 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol 2014; 64:e1–76. 8. Burton JH, Vinson DR, Drummond K, Strout TD, Thode HC, McInturff JJ. Electrical cardioversion of emergency department patients with atrial fibrillation. Ann Emerg Med 2004;44:20–30.
5. European Heart Rhythm Association, European Association for Cardio-Thoracic Surgery, Camm AJ, et al. Guidelines for the management of atrial
9. Xavier Scheuermeyer F, Grafstein E, Stenstrom R, Innes G, Poureslami I, Sighary M. Thirty-day outcomes of emergency department
fibrillation: the Task Force for the Management of Atrial Fibrillation of the European Society of Cardiology (ESC). Eur Heart J 2010;31:2369–429.
patients undergoing electrical cardioversion for atrial fibrillation or flutter. Acad Emerg Med 2010; 17:408–15.
11. Michael JA, Stiell IG, Agarwal S, Mandavia DP. Cardioversion of paroxysmal atrial fibrillation in the emergency department. Ann Emerg Med 1999;33:379–87. 12. Weigner MJ, Caulfield TA, Danias PG, Silverman DI, Manning WJ. Risk for clinical thromboembolism associated with conversion to sinus rhythm in patients with atrial fibrillation lasting less than 48 hours. Ann Intern Med 1997; 126:615–20. 13. Airaksinen KE, Grönberg T, Nuotio I, et al. Thromboembolic complications after cardioversion of acute atrial fibrillation: the FinCV (Finnish CardioVersion) study. J Am Coll Cardiol 2013;62: 1187–92. 14. Garg A, Khunger M, Seicean S, Chung M, Tchou P. Incidence of thromboembolic complications within 30 days of electrical cardioversion performed within 48 hours of atrial fibrillation onset. J Am Coll Cardiol EP 2016;2:XX.
JACC: CLINICAL ELECTROPHYSIOLOGY VOL.
-, 2016:-–-
-, NO. -, 2016
Katritsis and Josephson Anticoagulation for Cardioversion of Acute Onset Atrial Fibrillation
15. Stroke Risk in Atrial Fibrillation Working Group. Independent predictors of stroke in patients with atrial fibrillation: a systematic review. Neurology 2007;69:546–54.
18. Nagarakanti R, Ezekowitz MD, Oldgren J, et al. Dabigatran versus warfarin in patients with atrial fibrillation: an analysis of patients undergoing cardioversion. Circulation 2011;123:131–6.
16. Kleemann T, Becker T, Strauss M, Schneider S, Seidl K. Prevalence of left atrial thrombus and dense spontaneous echo contrast in patients with short-term atrial fibrillation <48 hours undergoing cardioversion: value of transesophageal
19. Flaker G, Lopes RD, Al-Khatib SM, et al., ARISTOTLE Committees and Investigators. Effi-
echocardiography to guide cardioversion. J Am Soc Echocardiogr 2009;22:1403–8. 17. Gaita F, Corsinovi L, Anselmino M, et al. Prevalence of silent cerebral ischemia in paroxysmal and persistent atrial fibrillation and correlation with cognitive function. J Am Coll Cardiol 2013;62:1990–7.
cacy and safety of apixaban in patients after cardioversion for atrial fibrillation: insights from the ARISTOTLE Trial (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation). J Am Coll Cardiol 2014;63: 1082–7. 20. Piccini JP, Stevens SR, Lokhnygina Y, et al., ROCKET AF Steering Committee & Investigators. Outcomes after cardioversion and atrial fibrillation
ablation in patients treated with rivaroxaban and warfarin in the ROCKET AF trial. J Am Coll Cardiol 2013;61:1998–2006. 21. Katritsis DG, Gersh BJ, Camm AJ. Anticoagulation in atrial fibrillation. Current concepts. Arrhythm Electrophysiol Rev 2015;4:100–7. 22. Cappato R, Ezekowitz MD, Klein AL, et al., on behalf of the X-VeRT Investigators. Rivaroxaban vs. vitamin K antagonists for cardioversion in atrial fibrillation. Eur Heart J 2014;35: 3346–55.
KEY WORDS anticoagulation, atrial fibrillation, cardioversion
3