Indian Journal of Anaesthesia

: 2017  |  Volume : 61  |  Issue : 9  |  Page : 712--720

Cardiac tachyarrhythmias and anaesthesia: General principles and focus on atrial fibrillation

Satyen Parida, Chitra Rajeswari Thangaswamy 
 Department of Anesthesiology and Critical Care, JIPMER, Puducherry, India

Correspondence Address:
Satyen Parida
Qr. No. D (II) 18, JIPMER Campus, Dhanvantari Nagar, Puducherry


Cardiac tachyarrhythmias are encountered commonly during the perioperative period and need to be promptly identified and appropriately managed by the anaesthesiologist. This review intends to highlight important aspects of these tachyarrhythmias and explore a temporal relationship between common medications employed in the perioperative period and their causation. Mechanisms of initiation of tachyarrhythmias, drugs that can trigger those, as well as their diagnosis and management, are also parts of the current review. Cardiac tachyarrhythmias may not always require treatment, and sometimes, aggressive management can trigger more serious types of arrhythmias. A thorough understanding of these tachyarrhythmias and their pathogenesis enables adopting a more objective approach, eschewing risks of inappropriate or unnecessary management strategies. We performed a MEDLINE search using combinations of MeSH terms such as 'cardiac', 'arrhythmias', 'anaesthesia', 'perioperative', 'tachyarrhythmias' and 'anaesthetic implications'. We reviewed the relevant publications with regard to cardiac tachyarrhythmias occurring in the perioperative period.

How to cite this article:
Parida S, Thangaswamy CR. Cardiac tachyarrhythmias and anaesthesia: General principles and focus on atrial fibrillation.Indian J Anaesth 2017;61:712-720

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Parida S, Thangaswamy CR. Cardiac tachyarrhythmias and anaesthesia: General principles and focus on atrial fibrillation. Indian J Anaesth [serial online] 2017 [cited 2021 Jan 24 ];61:712-720
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Cardiac arrhythmias are one of the most perturbing complications in the perioperative period.[1] Several pharmacological agents and non-pharmacological stimuli[2] during anaesthesia could result in cardiac arrhythmias. It is important for an anaesthesiologist to understand the pathophysiology and management of common cardiac arrhythmias. This review would focus on perioperative tachyarrhythmias during non-cardiac surgery and their management, with a special focus on atrial fibrillation (AF).

 Classification of Tachyarrhythmias

The cardiac impulse is generated from sinus node; it traverses through atrioventricular (AV) node, His bundle and Purkinje fibres and reaches the ventricles. Tachyarrhythmias occur due to abnormal impulse generation from the sinoatrial (SA) node, AV node or ventricles. In addition, abnormal impulse generation may be associated with abnormal conduction. Thus, tachyarrhythmias could be classified based on the rhythm (regular or irregular), site of origin (supraventricular or ventricular) and complexes on electrocardiogram (ECG) (narrow or broad complex). The classification of tachyarrhythmias into narrow or broad complex is based on the duration of the QRS complex and is shown in [Figure 1].{Figure 1}

 General Causes of Tachyarrhythmias during Anaesthesia

Several physical stimuli and many pharmacological agents could result in tachyarrhythmias. These factors may be classified according to patient, pathology, position, pharmacology and procedure [Table 1].{Table 1}

Most of the inhalational anaesthetics are associated with cardiac arrhythmias. Use of halothane during induction as well as maintenance of anaesthesia is associated with several dysrhythmias including atrial, nodal or ventricular tachycardia.[4] Hence, halothane induction in children has been largely replaced with sevoflurane which is safer.[5] During ophthalmic surgery, many types of arrhythmias are observed due to oculocardiac reflex.

Atropine is one of the commonly used drugs to treat bradycardia during general anaesthesia and also following spinal anaesthesia. It increases the heart rate leading to sinus tachycardia generally, but other arrhythmias including AV junctional tachycardia or ventricular bigeminy may also occur. These rhythms may convert to sinus tachycardia without any treatment.[6]

One of the risk factors for the development of torsades de pointes is QTc prolongation. Duma et al. observed that QTc prolongation occurs both after spinal and general anaesthesia which persists post-operatively.[7] Sevoflurane anaesthesia is also associated with prolongation of QTc interval.[8] There was no difference between sevoflurane and desflurane with respect to QTc prolongation.[9] Use of many other pharmacological agents could increase the QTc interval [Table 2]. Anaesthesiologists should be aware of these agents and manage their perioperative consequences accordingly.{Table 2}

Thoracic surgery is associated with an increased incidence of perioperative AF. In high-risk patients, prophylactic administration of amiodarone or magnesium sulphate could reduce the incidence of AF.[10]

 Management of Tachyarrhythmia

The most common causes for sinus tachycardia such as light planes of anaesthesia, lack of adequate analgesia, dehydration or wearing off of muscle relaxation should be ruled out before further differential diagnoses are considered. The management should include simultaneous assessment of underlying causes for the particular arrhythmia. These could be due to several factors as listed in [Table 1].

A schematic means to approach diagnosis of cardiac tachyarrhythmias is shown in [Figure 1]. Conventionally, cardiologists always require a 12-lead ECG to confirm the exact nature of arrhythmias. However, in the operating room, it is not always possible to get such an ECG done. Anaesthesiologists would have to make the diagnosis by looking at the ECG monitor. Some manufacturers would allow the grid lines and simultaneous ECG from other leads to be displayed on the monitor.

The presence of a P-wave will differentiate supraventricular tachycardia (SVT) from junctional tachycardia. In the presence of tachycardia, the P-wave may sometimes be overlapping on the T-wave. On many occasions, changing the sweep speed of ECG (from 50 to 25 mm/sec) may help identify the P-wave. However still, on several occasions, one would find the P-wave merging with the previous T-wave and thus unidentifiable even after altering sweep speeds. If the origin of impulse is above the AV node and below the SA node, the P-wave morphology might be biphasic. However, the absence of P-wave will not reliably rule out SVT. For example, rarely, one might encounter SVTs along with abnormal pathways. Alternatively, several of the vagal manoeuvres could be attempted. A few common cardiac tachyarrhythmias are depicted in [Figure 2] to serve as a reference.{Figure 2}

 Anti-Arrhythmic Drugs Classification and Mechanisms of Action (Vaughan Williams)

All anti-arrhythmic drugs act by modifying the action potential, which results from alteration of ion channels [Table 3]. The normal action potential has five phases. The most commonly used classification of anti-arrhythmics is the one proposed by Vaughan Williams [Table 3]. They are classified depending upon their action on the four phases of the cardiac cycle.{Table 3}


Patients with haemodynamic instability or those with signs of poor tissue perfusion would be treated straight away with electrical therapy. In patients who are otherwise stable, the clinical benefits of prompt cardioversion in the emergency department are less clear. The case in favour of emergency cardioversion in these patients hinges on the presumption that a regular sinus rhythm is preferable to the chaotic activity instituted by a tachyarrhythmia like AF.[11] However the basis for such observations is principally from anecdotal patient experiences and a single non-randomised trial.[12] Patients with structural heart diseases or refractory ventricular arrhythmias in spite of standard anti-arrhythmia management may need catheter ablation. Alternatively, implantable cardioverter defibrillator could be used preoperatively to manage these conditions. Thoracic epidural anaesthesia might reduce the incidence of ventricular arrhythmias by blocking cardiac sympathetic fibres.[13] Stellate ganglionectomy is another option to treat sympathetically mediated VT.[14] In patients undergoing thoracic surgeries, thoracic epidural infusion is believed to reduce the episodes of tachycardia.[15] Whenever there is a need for temporary pacing, the cardiologist may be called for intervention.

 Vagal Manoeuvres

The first line of treatment for SVTs is to attempt vagal manoeuvres such as Valsalva and carotid sinus massage (CSM). These manoeuvres will be of help only if the arrhythmia is dependent on the AV node. Valsalva manoeuvre is done by increasing the intrathoracic pressure to 30–40 mmHg. The Valsalva is generally divided into four separate phases: Phase 1, onset of straining and the beginning of an increase in intrathoracic pressure with glottic closure; Phase 2, persistent straining and maintenance of the increased intrathoracic pressure; Phase 3, release of breath-holding and glottic pressure with a sudden drop in the intrathoracic pressure and Phase 4, sudden increase in cardiac output and aortic pressure.

The cardioversion rate with this is less as is the requirement for other pharmacological management. Hence, a postural modification of the Valsalva manoeuvre has been evaluated. This included the conventional semi-recumbent position during the initiation of the Valsalva manoeuvre, followed by supine position and leg raise immediately after its release.[16]

 Carotid Sinus Massage

This is one of the vagal manoeuvres used in the treatment of SVTs. A recent review concluded that CSM should be considered first in the treatment of SVT.[17] CSM is performed by applying a steady pressure over right or left carotid sinus for 5–10 s. The complications of CSM include stroke. Hence, one has to rule out the presence of carotid bruit clinically before applying CSM. Alternatively, this could be ruled out by an ultrasound examination. Recently, a prospective crossover trial concluded that ultrasound-guided CSM is a suitable alternative to classical CSM.[18] An algorithmic approach to the acute treatment of regular SVT of unknown origin is shown in [Figure 3].{Figure 3}

 Perioperative Management of Atrial Fibrillation

AF is one of the most common arrhythmias in non-cardiac surgeries, especially in the elderly. AF occurs when there is an abnormal impulse formation or propagation from atrium due to structural or electrophysiological abnormalities. This could be classified as acute or chronic from the perspective of decision-making for management. Many modalities have been tried to prevent the incidence of AF including prophylactic beta-blockers, amiodarone, corticosteroids and magnesium. AF of acute onset is usually treated. An ECG with typical varying RR interval and absence of P-waves is diagnostic of AF.

 Classification of Atrial Fibrillation

AF is classified according to the onset and duration. Paroxysmal AF is defined as AF which terminates spontaneously or with any intervention within 7 days of onset. If it persists for >7 days, it is defined as persistent AF. Long-standing persistent AF continues for >12 months.

 Treatment of Atrial Fibrillation

The treatment of AF is focussed on five domains.[19] These include (a) presence of hemodynamic instability, (b) presence of precipitating factors, (c) anticoagulation, (d) rate control and (d) rhythm control. All these domains may not be applicable as such for perioperative AF that occurs for the first time. First onset of AF should be treated aiming for the restoration of haemodynamic stability while focussing on optimising the precipitating factors, rate control and rhythm control. Anticoagulation is not the initial focus intraoperatively.

 Rate Versus Rhythm Control

Pharmacological rate control is achieved with beta-blockers, digoxin, verapamil, diltiazem or a combination of drugs. Few antiarrhythmic agents such as amiodarone, dronedarone and sotalol have both rate control as well as rhythm control properties. The suggested algorithm for rate control is given in [Figure 4]. Even though the target for rate control is not very clear, it would generally be recommended to achieve a rate of <110 beats/min. The frequently used drugs include metoprolol and esmolol, followed by diltiazem and verapamil. These drugs are preferred over digoxin due to their rapid onset of action and also the effectiveness at high sympathetic tone. In addition, anaesthesiologists are more familiar with these drugs than digoxin when it comes to intravenous use.{Figure 4}

 Rhythm Control

Maintaining the sinus rhythm in AF is essential to preventing long-term complications of thrombus formation and stroke. It is believed that maintaining the sinus rhythm might improve the outcome. Many trials have compared the rate control only versus both rate and rhythm control and found no significant differences between the two approaches.[20],[21],[22],[23],[24] Hence, rhythm control may be attempted if rate control does not improve clinical symptoms. Amiodarone is the commonly used agent for restoring sinus rhythm. Before achieving rhythm control, anticoagulation of the patient should be considered. A basic algorithm for rhythm control of acute AF is shown in [Figure 5]. [Table 4] shows drugs which may be used for rate or rhythm control of AF.{Figure 5}{Table 4}

 Risk Stratification for Embolic Complications in Atrial Fibrillation

Risk stratification scores for individuals with non-valvular AF have been described to help clinicians estimate the adjusted stroke risk in these individuals and guide recommendations for antithrombotic therapy. CHADS2 is a simple, well-validated points-based risk assessment tool widely used to assess individual patient risk for stroke. The risk factors included in the CHADS2 score include congestive heart failure (1 point), hypertension (1 point), age >75 years (1 point), diabetes mellitus (1 point) and prior stroke/transient ischemic attack (TIA)/thromboembolism (2 points).[25]

The more recently introduced CHA2 DS2-VASc score has shown better predictive value in stroke-risk assessment. The CHA2 DS2-VASc score has been developed in an attempt to increase the predictive value for risk of stroke, especially in low-risk patients.[26] CHA2 DS2-VASc is now preferred over CHADS2 in the latest European 2012 and American 2014 guidelines.[27],[28] CHA2 DS2-VASc identifies 'major' risk factors, comprising stroke/TIA/thromboembolism and age ≥75 years (2 points each), and 'clinically relevant non-major' risk factors, comprising congestive heart failure, hypertension, diabetes mellitus, age 65–74 years, female gender and vascular disease (1 point each).[29] Recommendations to initiate treatment in patients based on the CHADS2 and CHA2 DS2-VASc have also been laid down.[26],[27],[30]


Patients with acute onset of AF, who are haemodynamically unstable, can undergo electrical cardioversion without anticoagulation. In patients with AF for >48 h, it is recommended to start oral anticoagulation for 3 weeks before cardioversion.[31],[32],[33] If patient needs early cardioversion, transoesophageal echocardiography should be done to rule out left atrial thrombus before attempting cardioversion. Vitamin K antagonists were the first and commonly used anticoagulants in AF. However, they need frequent monitoring of international normalised ratio to titrate the dose to achieve the therapeutic range. Once this is achieved, they are effective in preventing stroke. The use of newer non-Vitamin K antagonists such as direct thrombin inhibitors (dabigatran) and factor Xa inhibitors (apixaban, edoxaban and rivaroxaban) are increasing as they have a more predictable effect.

Newer non-Vitamin K antagonists inhibit the action of certain specific coagulation factors and are named accordingly as rivaroxaban, apixaban and edoxaban, which oppose the action of factor Xa, whereas dabigatran etixalate is a thrombin inhibitor [Figure 6].[34] These drugs score over warfarin in having comparatively shorter half-lives, predictable pharmacokinetics and pharmacodynamics, with less requirement for rigorous monitoring [Table 5].[35] The current evidence seems to suggest that the newer non-Vitamin K antagonists are identical to warfarin in prophylaxis of stroke or systemic embolisation in AF without escalated rates of intracranial bleed or mortality.[35],[36],[37],[38],[39],[40] These drugs have also demonstrated a better safety profile and efficacy in comparison to low molecular weight heparin for the prevention of deep venous thrombosis, following major orthopaedic surgery.[40],[41],[42],[43],[44] However, perioperative management of patients on these newer non-Vitamin K antagonists may be challenging in the settings of emergency surgery, trauma, bleeding or drug overdose.{Figure 6}{Table 5}

In patients receiving warfarin, bridging therapy with heparin may be recommended when the risk of thrombosis during withdrawal for elective surgery is high, but no clear guidelines state how to proceed in those at moderate risk of thrombosis. Bridging may be reserved for patients with mechanical heart valves and high risk for thromboembolism, history of recent stroke, TIA or CHADS2 score 5 or 6.[45] However, a recent randomised trial seems to suggest that bridging therapy may not provide added benefit and on the contrary may increase perioperative blood loss.[46] In patients on oral non-Vitamin K antagonists and a high risk of thrombosis, bridging may be initiated 12 h after the last dose.[47]

Reversal of warfarin effects can be achieved by Vitamin K as it can result in switching on of endogenous synthesis of Vitamin K-dependent clotting factors. If rapid reversal of warfarin effects is desired, as for impending surgery or for the management of major warfarin-induced bleeding, the options are between prothrombin complex concentrates (PCCs) and frozen plasma. PCC can reverse warfarin effects in no >6 h. Frozen plasma may be used as an alternative if PCC is either unavailable or contraindicated. Recommendations for warfarin reversal are shown in [Table 6].[48]{Table 6}

 Atrial Fibrillation in Pregnancy

Pregnant patients with pre-existing cardiac disease are more prone for AF. Among the options for rate control, placental transfer to foetus should be kept in mind. The safety of beta-blockers and calcium channel blockers are not well documented. Atenolol may cause growth retardation; hence, it is avoided. The first-line therapy for rate control in AF would be digoxin, followed by other drugs. For rhythm control, there are no randomised controlled trials. As rhythm control agents are associated with severe adverse foetal side effects, they are used only in emergency conditions. Electrical cardioversion is attempted where facilities are available to monitor foetal heart rate and also to intervene to manage foetal distress.

 Future Perspectives

Future pharmacological therapy of AF might include atrial selective modulation of ionic currents to avoid ventricular side effects and targeting other mechanisms involved in AF generation and maintenance with multifunctional compounds, with particular attention paid to avoid adverse effects in patients with left ventricular dysfunction. These include late or persistent sodium current inhibition, potassium channel activation, ultra-rapidly activating potassium current blockade, acetylcholine-regulated potassium current inhibition, sodium-calcium exchanger inhibition and hyperpolarisation-activated, cyclic nucleotide-gated pacemaker 'funny current' blockade, as provided by ivabradine. Owing to the heterogeneous mechanisms involved in tachyarrhythmia development, compounds with multiple sites of action including dronedarone, vernakalant and resveratrol could demonstrate better efficacy in their management.


The differentiation between a benign dysrhythmia and one that could lead to sudden haemodynamic decompensation is absolutely vital. Choice of anaesthetic agents might be of relevance in mitigating incidences of tachydysrhythmias. In patients who are haemodynamically unstable, emergent cardioversion or defibrillation is the management modality of choice, with anti-arrhythmic medications as indicated, to prevent recurrence of the particular tachyarrhythmia. In other patients who are haemodynamically stable, medications would be used first up. However, it must be remembered that management of cardiac tachyarrhythmias in the perioperative period does not always involve use of anti-arrhythmics, although their use should not be delayed when indicated.

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Conflicts of interest

There are no conflicts of interest.


1Fisher MD. Perioperative cardiac dysrhythmias. Anesthesiology 1997;86:1397-424.
2Alexander JP. Reflex disturbances of cardiac rhythm during ophthalmic surgery. Br J Ophthalmol 1975;59:518-24.
3Behnia R, Moss J, Graham JB, Linde HW, Roizen MF. Hemodynamic and catecholamine responses associated with extracorporeal shock wave lithotripsy. J Clin Anesth 1990;2:158-62.
4Alexander JP. Dysrhythmia and oral surgery. Br J Anaesth 1971;43:773-8.
5Blayney MR, Malins AF, Cooper GM. Cardiac arrhythmias in children during outpatient general anaesthesia for dentistry: A prospective randomised trial. Lancet 1999;354:1864-6.
6Carrow DJ, Aldrete JA, Masden RR, Jackson D. Effects of large doses of intravenous atropine on heart rate and arterial pressure of anesthetized patients. Anesth Analg 1975;54:262-6.
7Duma A, Pal S, Helsten D, Stein PK, Miller JP, Nagele P, et al. High-fidelity analysis of perioperative QTc prolongation. Anesth Analg 2016;122:439-48.
8Kim HJ, Lee HC, Jung YS, Lee J, Min JJ, Hong DM, et al. Effect of palonosetron on the QTc interval in patients undergoing sevoflurane anaesthesia. Br J Anaesth 2014;112:460-8.
9Min JJ, Lee J, Lee HC, Ryu HG, Shin M, Kim HJ, et al. A comparison of the effects of sevoflurane and desflurane on corrected QT interval prolongation in patients undergoing living donor liver transplantation: A prospective observational study. Transplant Proc 2016;48:96-101.
10Khalil MA, Al-Agaty AE, Ali WG, Abdel Azeem MS. A comparative study between amiodarone and magnesium sulfate as antiarrhythmic agents for prophylaxis against atrial fibrillation following lobectomy. J Anesth 2013;27:56-61.
11Stiell IG, Birnie D. Managing recent-onset atrial fibrillation in the emergency department. Ann Emerg Med 2011;57:31-2.
12Ballard DW, Reed ME, Singh N, Rauchwerger AS, Hamity CA, Warton EM, et al. Emergency department management of atrial fibrillation and flutter and patient quality of life at one month postvisit. Ann Emerg Med 2015;66:646-54.e2.
13Bourke T, Vaseghi M, Michowitz Y, Sankhla V, Shah M, Swapna N, et al. Neuraxial modulation for refractory ventricular arrhythmias: Value of thoracic epidural anesthesia and surgical left cardiac sympathetic denervation. Circulation 2010;121:2255-62.
14Methangkool E, Chua JH, Gopinath A, Shivkumar K, Mahajan A. Anesthetic considerations for thoracoscopic sympathetic ganglionectomy to treat ventricular tachycardia storm: A single-center experience. J Cardiothorac Vasc Anesth 2014;28:69-75.
15Licker M, Spiliopoulos A, Tschopp JM. Influence of thoracic epidural analgesia on cardiovascular autonomic control after thoracic surgery. Br J Anaesth 2003;91:525-31.
16Appelboam A, Reuben A, Mann C, Gagg J, Ewings P, Barton A, et al. Postural modification to the standard Valsalva manoeuvre for emergency treatment of supraventricular tachycardias (REVERT): A randomised controlled trial. Lancet 2015;386:1747-53.
17Collins NA, Higgins GL 3rd. Reconsidering the effectiveness and safety of carotid sinus massage as a therapeutic intervention in patients with supraventricular tachycardia. Am J Emerg Med 2015;33:807-9.
18Ha SM, Cho YS, Cho GC, Jo CH, Ryu JY. Modified carotid sinus massage using an ultrasonography for maximizing vagal tone: A crossover simulation study. Am J Emerg Med 2015;33:963-5.
19Kirchhof P, Benussi S, Kotecha D, Ahlsson A, Atar D, Casadei B, et al. 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur Heart J 2016;37:2893-962.
20Wyse DG, Waldo AL, DiMarco JP, Domanski MJ, Rosenberg Y, Schron EB, et al. A comparison of rate control and rhythm control in patients with atrial fibrillation. N Engl J Med 2002;347:1825-33.
21Van Gelder IC, Hagens VE, Bosker HA, Kingma JH, Kamp O, Kingma T, et al. A comparison of rate control and rhythm control in patients with recurrent persistent atrial fibrillation. N Engl J Med 2002;347:1834-40.
22Opolski G, Torbicki A, Kosior DA, Szulc M, Wozakowska-Kaplon B, Kolodziej P, et al. Rate control vs. rhythm control in patients with nonvalvular persistent atrial fibrillation: The results of the Polish How to Treat Chronic Atrial Fibrillation (HOT CAFE) Study. Chest 2004;126:476-86.
23Kong MH, Shaw LK, O'Connor C, Califf RM, Blazing MA, Al-Khatib SM. Is rhythm-control superior to rate-control in patients with atrial fibrillation and diastolic heart failure? Ann Noninvasive Electrocardiol 2010;15:209-17.
24Kotecha D, Kirchhof P. Rate and rhythm control have comparable effects on mortality and stroke in atrial fibrillation but better data are needed. Evid Based Med 2014;19:222-3.
25Gage BF, Waterman AD, Shannon W, Boechler M, Rich MW, Radford MJ, et al. Validation of clinical classification schemes for predicting stroke: Results from the national registry of atrial fibrillation. JAMA 2001;285:2864-70.
26Lip GY, Nieuwlaat R, Pisters R, Lane DA, Crijns HJ. Refining clinical risk stratification for predicting stroke and thromboembolism in atrial fibrillation using a novel risk factor-based approach: The euro heart survey on atrial fibrillation. Chest 2010;137:263-72.
27Camm AJ, Lip GY, De Caterina R, Savelieva I, Atar D, Hohnloser SH, et al. 2012 focused update of the ESC Guidelines for the 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. Eur Heart J 2012;33:2719-47.
28January CT, Wann LS, Alpert JS, Calkins H, Cigarroa JE, Cleveland JC Jr, 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.
29Lip GY, Halperin JL. Improving stroke risk stratification in atrial fibrillation. Am J Med 2010;123:484-8.
30Olesen JB, Torp-Pedersen C, Hansen ML, Lip GY. The value of the CHA2DS2-VASc score for refining stroke risk stratification in patients with atrial fibrillation with a CHADS2 score 0-1: A nationwide cohort study. Thromb Haemost 2012;107:1172-9.
31Schädlich PK, Schmidt-Lucke C, Huppertz E, Lehmacher W, Nixdorff U, Stellbrink C, et al. Economic evaluation of enoxaparin for anticoagulation in early cardioversion of persisting nonvalvular atrial fibrillation: A statutory health insurance perspective from Germany. Am J Cardiovasc Drugs 2007;7:199-217.
32Schmidt-Lucke C, Paar WD, Stellbrink C, Nixdorff U, Hofmann T, Meurer J, et al. Quality of anticoagulation with unfractionated heparin plus phenprocoumon for the prevention of thromboembolic complications in cardioversion for non-valvular atrial fibrillation. Sub-analysis from the Anticoagulation in Cardioversion using Enoxaparin (ACE) trial. Thromb Res 2007;119:27-34.
33Stellbrink C, Nixdorff U, Hofmann T, Lehmacher W, Daniel WG, Hanrath P, et al. Safety and efficacy of enoxaparin compared with unfractionated heparin and oral anticoagulants for prevention of thromboembolic complications in cardioversion of nonvalvular atrial fibrillation: The Anticoagulation in Cardioversion using Enoxaparin (ACE) trial. Circulation 2004;109:997-1003.
34Breuer G, Weiss DR, Ringwald J. 'New' direct oral anticoagulants in the perioperative setting. Curr Opin Anaesthesiol 2014;27:409-19.
35Eikelboom JW, Weitz JI. New anticoagulants. Circulation 2010;121:1523-32.
36Granger CB, Alexander JH, McMurray JJ, Lopes RD, Hylek EM, Hanna M, et al. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med 2011;365:981-92.
37Ruff CT, Giugliano RP, Braunwald E, Hoffman EB, Deenadayalu N, Ezekowitz MD, et al. Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: A meta-analysis of randomised trials. Lancet 2014;383:955-62.
38Gómez-Outes A, Terleira-Fernández AI, Calvo-Rojas G, Suárez-Gea ML, Vargas-Castrillón E. Dabigatran, rivaroxaban, or apixaban versus warfarin in patients with nonvalvular atrial fibrillation: A systematic review and meta-analysis of subgroups. Thrombosis 2013;2013:640723.
39Connolly SJ, Ezekowitz MD, Yusuf S, Eikelboom J, Oldgren J, Parekh A, et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med 2009;361:1139-51.
40Patel MR, Mahaffey KW, Garg J, Pan G, Singer DE, Hacke W, et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med 2011;365:883-91.
41Werth S, Halbritter K, Beyer-Westendorf J. Efficacy and safety of venous thromboembolism prophylaxis with apixaban in major orthopedic surgery. Ther Clin Risk Manag 2012;8:139-47.
42Kakkar AK, Brenner B, Dahl OE, Eriksson BI, Mouret P, Muntz J, et al. Extended duration rivaroxaban versus short-term enoxaparin for the prevention of venous thromboembolism after total hip arthroplasty: A double-blind, randomised controlled trial. Lancet 2008;372:31-9.
43Eriksson BI, Borris LC, Friedman RJ, Haas S, Huisman MV, Kakkar AK, et al. Rivaroxaban versus enoxaparin for thromboprophylaxis after hip arthroplasty. N Engl J Med 2008;358:2765-75.
44Lassen MR, Ageno W, Borris LC, Lieberman JR, Rosencher N, Bandel TJ, et al. Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty. N Engl J Med 2008;358:2776-86.
45Spyropoulos AC, Al-Badri A, Sherwood MW, Douketis JD. Periprocedural management of patients receiving a vitamin K antagonist or a direct oral anticoagulant requiring an elective procedure or surgery. J Thromb Haemost 2016;14:875-85.
46Douketis JD, Spyropoulos AC, Kaatz S, Becker RC, Caprini JA, Dunn AS, et al. Perioperative bridging anticoagulation in patients with atrial fibrillation. N Engl J Med 2015;373:823-33.
47Sié P, Samama CM, Godier A, Rosencher N, Steib A, Llau JV, et al. Surgery and invasive procedures in patients on long-term treatment with direct oral anticoagulants: Thrombin or factor-Xa inhibitors. Recommendations of the Working Group on Perioperative Haemostasis and the French Study Group on Thrombosis and Haemostasis. Arch Cardiovasc Dis 2011;104:669-76.
48Curtis R, Schweitzer A, van Vlymen J. Reversal of warfarin anticoagulation for urgent surgical procedures. Can J Anaesth 2015;62:634-49.