Perioperative challenges of atrial fibrillation.

REVIEW URRENT C OPINION

Perioperative challenges of atrial fibrillation Ivan Philip, Clarisse Berroe¨ta, and Isabelle Leblanc

Purpose of review The management of atrial fibrillation has seen marked changes in recent years. This is the result of better knowledge of the pathophysiology and risks factors for atrial fibrillation, better stratification for thromboembolic and bleeding risks, changing practices in anticoagulation management, and the development of new antiarrhythmic drugs. This article focuses on these new issues, with particular attention to their relevance in the perioperative period. Recent findings Improved understanding of the interaction between predisposing factors and the pathophysiological mechanisms of atrial fibrillation is changing management strategies. Preoperative identification of patients at risk for postoperative atrial fibrillation (POAF) is important so that measures such as ß-blockade may be introduced to prevent its occurrence. When POAF does occur, cardioversion is preferred in unstable patients and amiodarone is the most commonly used drug. Owing to the transient nature of POAF and excessive bleeding risk immediately postsurgery, anticoagulation should be used with caution in these patients. The perioperative management of patients on chronic oral anticoagulants is guided by weighing the risk of thromboembolic complications against the risk surgical bleeding. Risk stratification scoring systems and published guidelines facilitate decision-making. New oral anticoagulants offer potentially improved safety profiles over traditional agents; however, their optimal management in the perioperative period remains unknown. Summary Better knowledge of the pathophysiology of atrial fibrillation and improved awareness of the risks associated with this frequent arrhythmia are continuing to improve the management of patients with chronic atrial fibrillation and new-onset atrial fibrillation in the perioperative period. As with most complex disease processes, treatment decisions must be individualized for each patient and clinical context. Keywords anticoagulation, atrial fibrillation, bleeding, new-onset perioperative atrial fibrillation, stroke, thromboembolism

INTRODUCTION Perioperative management of patients with a history of atrial fibrillation or new-onset atrial fibrillation remains a frequent challenge. In this review, we will discuss the epidemiology of atrial fibrillation. We will also review the management of atrial fibrillation in the perioperative period, including the management of oral anticoagulation (OAC) and new-onset postoperative atrial fibrillation (POAF).

fibrillation are faced with several issues: increased hemodynamic instability, increased thromboembolic risk, and the management of OAC with or without heparin bridging [3]. The incidence of new-onset POAF varies considerably between studies [4 ]. In noncardiac, nonthoracic surgery, POAF occurs less frequently: from 1% after minor surgery to 5–10% after vascular or large colorectal surgery. New-onset POAF occurs principally after thoracic and cardiac surgery. Concerning thoracic surgery, the incidence of atrial &&

INCIDENCE Atrial fibrillation is the most common sustained arrhythmia, increasing in prevalence and incidence [1 ,2] mainly because of the aging population. Atrial fibrillation can be classified into three forms: paroxysmal, persistent, and permanent (Fig. 1). Anesthesiologists dealing with a patient with a history of atrial &&

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Service d’Anesthe´sie, Institut Mutualiste Montsouris, Paris Ce´dex, France Correspondence to Ivan Philip, Service d’Anesthe´sie, Institut Mutualiste Montsouris, Boulevard Jourdan, 75674 Paris Ce´dex 14, France. Tel: +33 1 56616263; fax: +33 1 56616663; e-mail: [email protected] Curr Opin Anesthesiol 2014, 27:344–352 DOI:10.1097/ACO.0000000000000070 Volume 27 Number 3 June 2014

Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.

Perioperative challenges of atrial fibrillation Philip et al.

KEY POINTS Chronic oral anticoagulation reduces the risk of stroke in moderate and high-risk patients with atrial fibrillation and a growing number of patients will receive these treatments. Risk stratification of patients with atrial fibrillation for stroke or thromboembolism and bleeding has been improved, and new simple scoring systems have emerged.

valve surgery, and 50% after combined procedures. New procedures, such as transcatheter aortic valve implantation (TAVI), may reduce this incidence: 15% with a femoral approach [8,9]. After off-pump CABG, the incidence of POAF is probably lower than after conventional on-pump CABG [10,11].

RISK FACTORS The risk factors for nonperioperative atrial fibrillation include established risk factors and emerging ones [1 ]. Traditional risk factors include age, hypertension, male sex, as well as comorbidities such as hyperthyroidism, diabetes, and cardiac disease, particularly valve dysfunction. However, traditional risk factors account for only a portion of the risk of developing atrial fibrillation [12]. Emerging risk factors include obesity, obstructive sleep apnea, alcohol abuse, and chronic kidney disease. Furthermore, a link between atrial fibrillation susceptibility and genetic processes has been recently uncovered [2,13,14]. The most consistent predictor for the development of POAF is advanced age [4 ,7,15,16]. Advanced age is associated with degenerative and inflammatory modifications in atrial anatomy, such as dilation and fibrosis. Other risk factors for POAF have also been reported with some degree of variability. These include hypertension, obesity, chronic obstructive pulmonary disease, and genetic factors (Fig. 2). The fact that risk factors for POAF are quite similar to the classical risk factors for atrial fibrillation reinforces the hypothesis that the occurrence of POAF is strongly determined by the pre-existence of an atrial fibrillation substrate, marked by structural remodeling and changes in electrophysiology. The time course of POAF (70% in the first 4 postoperative days) highlights the importance of temporary surgery-induced factors such as inflammation, sympathetic stimulation (probably the most relevant). and oxidative stress. Finally, genetic factors appear to predispose some patients to the occurrence of POAF. With these conditions present, a triggering factor then generates the occurrence of POAF [17]. The interaction between pre-existing substrates and postoperative mechanisms is also highlighted by recent findings showing that although the duration of POAF is generally short, its occurrence increases the risk of future atrial fibrillation and is associated with increased long-term cardiovascular mortality after cardiac as well as vascular and thoracic surgery [18–20]. &&

Anesthesiologists must be aware of recent guidelines on perioperative management of anticoagulation in patients with atrial fibrillation to reduce the risk of perioperative thromboembolic and/or bleeding complications (e.g., bridging of chronic OAC by heparin). New-onset POAF is very frequent after thoracic and cardiac surgeries and is associated with an increased morbidity and length of stay; therefore, it is preferable to prevent its occurrence rather than treat it once it has occurred.

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Considering the usual short duration of POAF and the increased postoperative risk of bleeding, anticoagulation should be used with caution in the immediate postoperative setting.

fibrillation is very low after exploratory thoracotomy or minimal resections of the lung, but higher after larger lung resections or esophagogastrectomy (10–30%) [5]. Whether video-assisted approaches to lung resection reduce the incidence of POAF is controversial [5,6]. The incidence of POAF after cardiac surgery remains high [4 ,7]: 30% after isolated coronary artery bypass grafting (CABG) surgery, 40% after &&

First diagnosed episode of atrial fibrillation

Paroxysmal (usually ≤ 48 h)

Persistent (> 7 days or requires CV)

Permanent (accepted)

PROGNOSIS OF ATRIAL FIBRILLATION FIGURE 1. Classification of atrial fibrillation. Adapted with permission from [22]. Atrial fibrillation is classified based on duration and evolution.

Atrial fibrillation independently increases the risk of mortality and morbidity because of stroke, thromboembolism, and congestive heart failure. It also

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Anesthesia and medical disease

Risk factors for POAF

Risk factors for AF Traditional: age, hypertension, male sex, diabetes, valvular heart disease, heart failure, coronary heart disease, cardiac surgery, hyperthyroidism Emerging: obesity, chronic kidney disease, sleep apnea, excess alcohol consumption, genetic factors

Advancing age, left atrial enlargement, obesity, previous history of AF, male gender, hypertension, COPD, heart failure, withdrawal of β-blockers, genetic factors

Pre-existing substrates (left atrium)

Perioperative factors for POAF Surgical (atrial suture or ischemia) Inflammation, oxidative stress Sympathetic stimulation Acute volume changes

Postoperative atrial fibrillation

Triggering factor Electrolyte imbalance Atrial premature contraction Enhanced adrenergic or vagal stimulation

FIGURE 2. Risk factors for atrial fibrillation and postoperative atrial fibrillation (POAF), adapted from refs. [4 ,7]. Risk factors for atrial fibrillation and POAF are quite similar. The interaction between pre-existing substrates at the level of the left atrium and surgical-induced factors likely accounts for the development of POAF. &&

results in impaired quality of life, resulting in a high healthcare cost and public health burden [1 ]. Stroke is the most devastating complication of atrial fibrillation, and its incidence can be decreased through the use of antithrombotic therapy [21]. Atrial fibrillation increases the risk of stroke fivefold, but this risk is not homogenous and changes cumulatively with the presence of concomitant stroke risk factors. Recent guidelines on stroke risk stratification in patients with nonvalvular atrial fibrillation have shifted toward identification of truly low-risk patients with atrial fibrillation who do not need antithrombotic therapy. In patients with one or more risk factors for stroke, OAC therapy should be considered [22]. The score most commonly used to evaluate stroke risk is the CHADS2 score, but it tends to falsely identify a large number of patients at low risk [23]. CHA2DS2-VASc is a refined clinical scoring tool that more accurately identifies those truly low-risk patients who do not benefit from thromboprophylaxis [24] (Fig. 3). Compared with the CHADS2 score, this scoring system considers advanced age and vascular disease as additional risk factors [25 ,26,27]. Recent studies have also pointed out the link between renal insufficiency and an increased risk of bleeding in anticoagulated patients with atrial fibrillation (HASBLED score) [28–30]. Interestingly, despite international guidelines, studies have shown that many patients with atrial fibrillation do not receive all guideline-recommended therapies [31–36]. Typically, young lowrisk patients are often overtreated, whereas older &&

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patients are undertreated, principally by the fear of the occurrence of bleeding. Furthermore, there is still a significant discrepancy in the management of anticoagulation in patients with atrial fibrillation according to the specialty of the physicians [35,36]. These results highlight the importance of knowledge of these new changes and guidelines by the anesthesiologists [37 ]. Just as in the medical setting, new-onset POAF after cardiac and thoracic surgery remains associated with an increased risk of mortality and morbidity, a prolonged length of stay in hospital, and substantial increase in medical costs [4 ,7]. It increases the risk for postoperative thromboembolic event and stroke – although this point is still controversial – [38–40], hemodynamic instability, and iatrogenic complications associated with therapeutic interventions. These consequences underline the necessity of better prevention against POAF. &

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MANAGEMENT OF ARRHYTHMIA When POAF occurs, it is necessary to decide whether and how to convert the rhythm and how to manage anticoagulation in the perioperative period. As treatment of POAF is complex and its occurrence is a risk factor for poor outcomes, identifying patients at high risk for POAF and taking steps to prevent it from occurring is ideal.

New-onset postoperative atrial fibrillation The treatment of POAF includes four steps: management of co-existing medical conditions (e.g., Volume 27 Number 3 June 2014


Perioperative challenges of atrial fibrillation Philip et al.

(a) Risk factor

Score

Congestive heart failure/LV dysfunction

1

Hypertension

1

Age ≥ 75

2

Diabetes mellitus

1

Stroke/TIA/thrombo-embolism

2

Vascular disease

1

Age 64–74

1

Sex category (i.e. female sex)

1

Maximum score

9

(b) Clinical characteristic Hypertension Abnormal renal and liver function (1 point each)

Score 1 1 or 2

Stroke

1

Bleeding

1

Labile INRs

1

Elderly (age > 75 years) Drugs or alcohol (1 point each) Maximum score

1 1 or 2 9

FIGURE 3. (a) Risk stratification for stroke and thromboembolism by the CHA2DS2-VASc score. Patients with a score of 0 do not need chronic anticoagulation. For any other score level, there is a benefit from chronic anticoagulation. (b) Risk stratification for bleeding by the HAS-BLED score. The risk of major bleeding within 1 year increases from 1 per 100 patient-years (score 0 or 1) to 12.5 (score 5). INR, international normalized ratio; TIA, transient ischemic attack.

hypoxia, electrolyte imbalances); treatment of arrhythmia; search for underlying postoperative complications (e.g., sepsis); and consideration of anticoagulation therapy. Because POAF is often transient and self-limiting, some patients – particularly after noncardiac surgery – will receive neither antiarrhythmic drug (AAD) nor anticoagulation therapy [4 ,7]. When the decision is made to use AAD, amiodarone is the drug of choice for conversion of POAF [41,42]. Studies evaluating rhythm conversion in critically ill populations outside of cardiac surgery are lacking [43]. Thus, recommendations are guided primarily by medical cardiology and postoperative thoracic and/or cardiac surgery studies [22,44,45]. Cardioversion is generally preferred in symptomatic patients or when ventricular response is difficult to control. Restoration of sinus rhythm by electrical cardioversion is recommended in hemodynamically &&

unstable patients. Amiodarone is effective in converting atrial fibrillation to sinus rhythm, but with a delayed action. It should be used with caution – if at all – in patients with severe pulmonary disease or after pneumonectomy [44]. Although associated mainly with age and chronic administration, acute pulmonary toxicity has been reported after administration of high doses of amiodarone, with severe outcomes in patients with low pulmonary reserve. Conversion is more rapid with flecainide than with amiodarone; nevertheless, flecainide is contraindicated in patients with any form of structural heart disease. Other agents that have been used to convert atrial fibrillation to sinus rhythm include ibutilide (but with a risk of severe drug-induced arrhythmia and not available in many European countries), sotalol, and vernakalant [22,46]. For stable patients, a rate-control strategy may be proposed as a first line of action, using an atrioventricular nodal-blocking agent such as a b-blocker drug or a nondihydropyridine calcium-channel antagonist (diltiazem or verapamil). Amiodarone can also be used to decrease heart rate, independently of its rate-conversion effect. If atrial fibrillation does not convert to sinus rhythm within 24 h, then a rhythm-control strategy should be attempted, in conjunction with anticoagulation. Vernakalant is the first marketed drug with relative atrial selectivity, which should increase patient safety. For patients with recent-onset atrial fibrillation, vernakalant resulted in successful cardioversion within the first 90 min in 52% of patients compared with 5% in the amiodarone group (median time of 11 min in responders) [47]. Similar results have been reported after cardiac surgery [48]. A low rate of adverse events has been reported with this drug, indicating a higher safety profile as compared with other AADs. Further studies are warranted to determine the role of vernakalant in the treatment of POAF.

Prevention Many studies have evaluated the effectiveness of pharmacologic and nonpharmacologic interventions to prevent or decrease the incidence of POAF after cardiac surgery and guidelines regarding the prevention of atrial fibrillation have been published by the Society for Thoracic Surgeons and American College of Cardiology/American Heart Association [22,44,45]. Nevertheless, three recent studies have demonstrated that the use of atrial fibrillation prophylaxis before surgery is less than expected and still varies significantly between institutions [49 ,50,51]. Current evidence strongly supports the continuation of perioperative b-blocker therapy or its


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initiation in naı¨ve patients, unless contraindicated (>1 week preoperatively). Prophylactic amiodarone also decreases the incidence of POAF after CABG surgery and may be added in patients at high risk for atrial fibrillation. Sotalol reduces the incidence of POAF, but its use in this setting remains limited by concern over adverse effects. As hypomagnesemia is an independent risk factor for POAF, prophylactic intravenous magnesium may be indicated [52]. Among non-AADs, statins [53] and corticosteroids have been extensively studied in the prevention of POAF, mainly because of their beneficial anti-inflammatory effects. Although corticosteroids have been associated with a net reduction in the incidence of POAF, they remain used infrequently because of the risk of adverse effects. Nevertheless, a recent meta-analysis has suggested that low-dose corticosteroids are effective at reducing the incidence of POAF without increasing infections [54]. There is some evidence that colchicine is effective at reducing POAF [55]; a follow-up trial evaluating its use pre and postoperatively is ongoing [56]. Finally, the impact of a multiple regimen including b-blockers, amiodarone, statins, magnesium, and corticosteroids remains to be evaluated [7,22,44,56,57].

MANAGEMENT OF ANTICOAGULATION Perioperative management of anticoagulant therapy is a complex topic that must weigh the risk of thromboembolism and stroke against the risk of surgical bleed. Three aspects of anticoagulation will be discussed: its use in the context of new-onset POAF, perioperative management of patients on chronic anticoagulant (AC) for atrial fibrillation, and new oral AC.

New-onset postoperative atrial fibrillation Current guidelines for antithrombotic therapy are based on the duration of atrial fibrillation, the presence (or absence) of risk factors for stroke and thromboembolism (Fig. 3), as well an assessment of bleeding risk [22,45]. There is an increased risk for thromboembolism following cardioversion. Therefore, AC is considered mandatory before elective cardioversion for atrial fibrillation of more than 48 h or of unknown duration; in this case, OAC should be given for at least 3 weeks before cardioversion. More recently, transesophageal echocardiography-guided therapy with short-duration heparin therapy has been proposed as an alternative. In patients with a definite atrial fibrillation onset less than 48 h and with risk factors for stroke, cardioversion can be performed expediently under the cover of unfractionated intravenous heparin or a 348


weight-adjusted therapeutic dose of low molecular weight heparin (LMWH). The duration of OAC therapy after cardioversion will depend on the presence of risk factors for stroke: 4 weeks (because of some degree of stunning of the atria) or lifelong. For patients with atrial fibrillation duration that is clearly less than 48 h and with no thromboembolic risk factors, heparin therapy may be considered pericardioversion (not necessary in Canadian guidelines [58]), with no postcardioversion anticoagulation. Application of these medical recommendations to new-onset POAF is guided by two main factors: the usually transient and self-limited duration of new-onset POAF and the increased risk of bleeding in the postoperative period. As POAF often lasts less than 24 h, therapeutic doses of heparin are generally not required. As a general rule, therapeutic doses of anticoagulation are only given for prolonged (>24–48 h) and/or frequent atrial fibrillation episodes. The optimal duration of anticoagulation in patients who develop POAF is also unclear. It has been suggested that anticoagulation therapy should be continued for approximately 4 weeks after the return of sinus rhythm, at least in high-risk patients [7,57]. The difficulty in managing anticoagulation for new-onset atrial fibrillation after noncardiac surgery has been highlighted by a recent study [59]. Even though this retrospective study has numerous limitations, it confirms that in patients with POAF after a major general surgery, anticoagulation should be used with caution. Indeed, in cases of POAF, anticoagulation significantly increased the risk of bleeding complications (9.7 vs. 5.2%, P ¼ 0.009).

Chronic oral anticoagulants in patients with atrial fibrillation Patients receiving long-term OAC therapy often undergo elective invasive procedures requiring treatment interruption (about 10% per year) [60,61,62 ]. The risk of a thromboembolic event occurring while the antithrombotic agent is reduced or stopped must be weighed against the goal of a reduced periprocedural risk of bleeding. Few prospective, randomized, controlled studies on this topic have been performed or are ongoing [37 ,63 ]. Recently, Siegal et al. [64 ] performed a metaanalysis to evaluate the safety and efficacy of periprocedural anticoagulant bridging and found that heparin bridging increased the risk for bleeding without reducing thromboembolic events. This conclusion must be interpreted with caution because of the heterogeneity of the included data, &

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Perioperative challenges of atrial fibrillation Philip et al. &

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[68 ,69 ]. Interestingly, a HAS-BLED score of 3 or more was identified as an independent predictor of bleeding [68 ]. The first question for the anesthesiologist is whether the procedure can be performed without any change in OAC, such as for cataract surgery or other superficial surgeries (Fig. 4). If the procedure requires near-normal hemostasis, and when the thromboembolic risk is deemed to be low, OAC can be stopped or reduced for the surgery. In all other cases, heparin bridging is the most appropriate option, and is best performed using institutional protocols that follow available guidelines [70]. In most cases, bridging can be accomplished using LMWH. The exact threshold at which a patient with nonvalvular atrial fibrillation should be considered at high enough risk for a thromboembolic event to receive heparin bridging before surgery remains to be determined. Ongoing studies may perhaps answer this question.

reflecting the high variation in current clinical practice [65]. Ongoing randomized trials may answer the many questions that remain unanswered about periprocedural anticoagulation. For example, Birnie et al. [63 ] recently reported that pacemaker or defibrillator surgery can be safely performed without warfarin interruption, with a reduced incidence of device-pocket hematoma compared with bridging therapy with heparin. Nevertheless, physicians must keep in mind that persistent atrial fibrillation remains a risk factor for perioperative stroke in patients without anticoagulation [66,67]. Guidelines take into account the balance between perioperative thromboembolic and bleeding risks. The former may be assessed by the existence of risk factors for stroke; the assessment of the latter comes from a combination of surgical and patient-specific factors. Two recent studies have evaluated the risk of periprocedural bleeding

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Yes

Can procedure be safely performed on VKA?

Exclude excessive INR Proceed

No Emergency?

Yes

> 12 h : Vit K 2–5 mg orally or IV < 12 h : PCC (25 IU.FIX.Kg–1) + Vit K

No Assessment for TE risk?

Low*

Preoperative § No bridging therapy required § Stop VKA 5 days prior § INR before surgery

Moderate or high**

Preoperative § Assess creatine clearance, INR, platelet count § Stop VKA 5 days prior § Therapeutic-dose LMWH began 3 days before: once daily (twice if high risk)*** § INR before surgery

Postoperative § Assess hemostasis § DVT prophylaxis § Progressive increase in LMWH § Assess creatine clearance, platelet count § Restart VKA as soon as possible

FIGURE 4. Management of patients treated with VKA for atrial fibrillation requiring invasive procedures. Adapted with permission from [3]. The management of VKA and decision to use bridging therapy in patients with atrial fibrillation involves weighing the risk of thromboembolism against the risk of surgical bleeding. Many superficial surgeries, such as cataract procedures, may be performed without interrupting VKA therapy. If the patient is deemed to be at low thromboembolic risk, VKA may be stopped without bridging therapy. If the patient is deemed to be at moderate or high risk of thromboembolism, then bridging therapy with LMWH is usually employed. When a patient on VKA therapy requires emergency surgery with high bleeding risk, vitamin K or PCC concentrate may be given. Low thromboembolic risk: patients with nonvalvular atrial fibrillation and CHADS2 (or CHA2DS2-VASc) score 2 (threshold not validated by prospective studies). Moderate or high thromboembolic risk: valvular atrial fibrillation, recent stroke or transient ischemic attack, CHA2DS2-VASc 3. Unfractionated heparin remains used in some very high-risk patients or in patients with severe renal failure. DVT, deep venous thrombosis; INR, international normalized ratio; LMWH, low molecular weight heparin; PCC, prothrombin complex concentrate; VKA, vitamin K antagonist. 0952-7907 ß 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins


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New oral anticoagulant Vitamin K antagonists (VKAs) significantly reduce ischemic stroke risk in patients with atrial fibrillation, but has numerous limitations, including most notably the need for frequent monitoring of therapeutic level. New OACs (NOACs), such as dabigatran, rivaroxaban, and apixaban have emerged as an alternative to VKA in patients with nonvalvular atrial fibrillation. NOAC may be superior to VKA for this indication, reducing the composite endpoint of stroke or systemic embolism and lowering all-cause mortality, with the benefit resulting largely from fewer hemorrhagic strokes [71 ,72]. A complete review of these agents is beyond the scope of this article; nevertheless, anesthesiologists must be familiar with these NOACs, as a growing number of patients presenting for surgery will be taking these medications [73 ]. As with any antithrombotic therapy, physicians must be aware of guidelines about the management of patients undergoing a planned surgical intervention, an urgent surgical intervention, or a bleeding episode with or without drug overdose. Renal function has to be assessed, as all of the currently available agents are eliminated primarily by the kidney. As yet, no reversal agents are available for these drugs; however, phase II trials with specific antidotes are currently ongoing [74 ,75]. Current guidelines for bridging NOAC before major surgery are cautious [37 ,76 ]. European and French societies recommend a schema similar to VKA management, with an interruption of oral therapy for 4 days before surgery and heparin bridging if necessary [77,78,79 ]. In the postoperative period, reintroduction of NOAC is advised only when the risk of bleeding is eliminated, given that reversal is not yet possible.

Acknowledgements None. Conflicts of interest Disclosure: I.P. reports consultant fees from Bayer.

REFERENCES AND RECOMMENDED READING Papers of particular interest, published within the annual period of review, have been highlighted as: & of special interest && of outstanding interest 1. Lip GY, Tse HF, Lane DA. Atrial fibrillation. Lancet 2012; 379:648–661. &&

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CONCLUSION Atrial fibrillation is a commonly encountered arrhythmia in the perioperative period. Preoperative identification of patients at high risk for developing POAF offers the opportunity to take preventive measures to prevent its occurrence. When atrial fibrillation does occur, management decisions include the need for cardioversion, AAD, and anticoagulation. For patients with chronic atrial fibrillation presenting for surgery, the perioperative management of OAC must weigh the risk of stroke and thromboembolism against the risk of surgical bleeding, and treatment decisions have to be individualized to the patient and clinical context. NOACs present new challenges for anticoagulation management in the perioperative period. 350


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Anesthesia and medical disease 65. Gallego P, Apostolakis S, Lip GY. Bridging evidence-based practice and practice-based evidence in periprocedural anticoagulation. Circulation 2012; 126:1573–1576. 66. Chen S, Liu J, Pan W, et al. Thromboembolic events during the perioperative period in patients undergoing permanent pacemaker implantation. Clin Cardiol 2012; 35:83–87. 67. Garcia DA, Regan S, Henault LE, et al. Risk of thromboembolism with shortterm interruption of warfarin therapy. Arch Intern Med 2008; 168:63–69. 68. Omran H, Bauersachs R, Rubenacker S, et al. The HAS-BLED scorepredicts & bleedings during bridging of chronic oral anticoagulation. Results from the national multicentre BNK Online bRiDging REgistRy (BORDER). Thromb Haemost 2012; 108:65–73. The authors report a prospective, observational, multicentre registry dealing with perioperative management of patients receiving long-term OAC. Interestingly, a HAS-BLED score (validated in the medical setting) was highly predictive of bleeding events. 69. Tafur AJ, McBane R 2nd, Wysokinski WE, et al. Predictors of major bleeding & in peri-procedural anticoagulation management. J Thromb Haemost 2012; 10:261–267. This is a prospective, observational, monocenter study addressing peri-procedural anticoagulation management in order to assess predictors of major bleeding. 70. Spyropoulos AC, Douketis JD, Gerotziafas G, et al. Periprocedural antithrombotic and bridging therapy: recommendations for standardized reporting in patients with arterial indications for chronic oral anticoagulant therapy. J Thromb Haemost 2012; 10:692–694. 71. Dogliotti A, Paolasso E, Giugliano RP. Current and new oral antithrombotics in & nonvalvular atrial fibrillation: a network meta-analysis of 79 808 patients. Heart 2013; 100:396–405. In this meta-analysis, the authors compare the rates of stroke and the composite of ischemic stroke or systemic embolism and mortality in patients treated with VKA, NOAC, or antiplatelet regimens for nonvalvular atrial fibrillation. 72. Dogliotti A, Paolasso E, Giugliano RP. Novel oral anticoagulants in atrial fibrillation: a meta-analysis of large, randomized, controlled trials vs warfarin. Clin Cardiol 2013; 36:61–67.

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73. Levy JH, Faraoni D, Spring JL, et al. Managing new oral anticoagulants in the perioperative and intensive care unit setting. Anesthesiology 2013; 118:1466– 1474. This is a thorough review, dealing with perioperative management of patients treated with NOAC. 74. Majeed A, Hwang HG, Connolly SJ, et al. Management and outcomes of major & bleeding during treatment with dabigatran or warfarin. Circulation 2013; 128:2325–2332. This is a retrospective comparison of the management and prognosis of major bleeding in 1121 patients treated with dabigatran or warfarin, enrolled in five phase III trials. A limitation of the study is that prothrombin complex concentrate was used infrequently to treat bleeding in either group. However, the results suggest that dabigatran offers an alternative to warfarin and may confer a lower bleeding risk, especially in patients undergoing intracranial procedures. 75. Majeed A, Schulman S. Bleeding and antidotes in new oral anticoagulants. Best Pract Res Clin Haematol 2013; 26:191–202. 76. Heidbuchel H, Verhamme P, Alings M, et al. European Heart Rhythm Asso&& ciation: Practical Guide on the use of new oral anticoagulants in patients with nonvalvular atrial fibrillation. Europace 2013; 15:625–651. This is a review on the use of NOAC in patients with nonvalvular atrial fibrillation. 77. Pernod G, Albaladejo P, Godier A, et al. Management of major bleeding complications and emergency surgery in patients on long-term treatment with direct oral anticoagulants, thrombin or factor-Xa inhibitors. Ann Fr Anesth Reanim 2013; 32:691–700. 78. Sie P, Samama CM, Godier A, et al. Surgery and invasive procedures in patients on long-term treatment with oral direct thrombin or factor Xa inhibitors. Ann Fr Anesth Reanim 2011; 30:645–650. 79. Kozek-Langenecker SA, Afshari A, Albaladejo P, et al. Management of severe && perioperative bleeding: guidelines from the European Society of Anaesthesiology. Eur J Anaesthesiol 2013; 30:270–382. Theses are guidelines of the European Society of Anesthesiology for the management of severe perioperative bleeding and anticoagulation and hemostatic agents. &



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