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Atrial fibrillation in adults: Selection of candidates for anticoagulation

Atrial fibrillation in adults: Selection of candidates for anticoagulation
Literature review current through: Jan 2024.
This topic last updated: Jan 11, 2024.

INTRODUCTION — Atrial fibrillation (AF) is a major cause of morbidity and mortality in adults. While ischemic stroke due to embolization of left atrial thrombi is the most frequent clinical manifestation of embolization, embolization to other locations in the systemic circulation (and in the pulmonary circulation from right atrial thrombi) also occurs but is less commonly recognized. Stroke associated with AF tends to be more extensive/larger than stroke related to carotid artery disease. Chronic oral anticoagulation (OAC) is recommended to reduce the risk of thromboembolism for most patients with AF. However, such therapy is associated with an increased risk of bleeding, and recommendations for its use must take both benefit and risk into account through shared decision-making with the patient. (See "Stroke in patients with atrial fibrillation".)

This topic will focus on identifying which patients with AF require long-term/chronic OAC with either vitamin K antagonist (VKA; eg, warfarin) or direct oral anticoagulants (DOAC; also referred to as non-vitamin K oral anticoagulants [NOAC]). The discussion here excludes patients with rheumatic mitral stenosis that is severe or clinically significant (mitral valve area ≤1.5 cm2), a bioprosthetic valve (surgical or bioprosthetic) within the first three to six months after implantation, or a mechanical heart valve. Management for patients with these valve conditions is briefly discussed in a section below that provides links to related topics. (See 'Patients with valvular heart disease' below.)

Other potentially relevant topics to the reader include:

Choice of OAC for AF (see "Atrial fibrillation in adults: Use of oral anticoagulants")

(See "Prevention of embolization prior to and after restoration of sinus rhythm in atrial fibrillation".)

(See "Stroke in patients with atrial fibrillation".)

(See "Atrial fibrillation: Left atrial appendage occlusion".)

(Related Pathway(s): Atrial fibrillation: Anticoagulation for adults with atrial fibrillation.)

APPROACH TO DECIDING WHETHER TO ANTICOAGULATE

Decision-making based upon risk assessment — A first step in deciding which patients with AF should receive long-term oral anticoagulation (OAC) is to assess the individual patient’s risks of thromboembolism and bleeding along with patient preferences. Long-term anticoagulation lowers the risk of clinical embolization in patients with AF, but its use is associated with an increased risk of bleeding.

The benefits and risks of OAC with respect to reduction in risk of stroke and increment in risk of bleeding must be carefully considered and discussed with each patient. The greater the estimated reduction in absolute stroke risk compared with the increase in absolute risk of life-threatening or severely debilitating bleeding (such as intracranial hemorrhage), the more likely a patient is to benefit from long-term OAC. The benefit generally outweighs the risk for all but those with the lowest risk of thromboembolism. In cases of more balanced stroke reduction and bleeding risks, OAC is less likely to provide a net benefit. Risk scores are commonly used to assess thromboembolic and bleeding risks, although these tools are subject to a number of limitations. (See 'CHA2DS2-VASc score' below and 'Bleeding risk' below.) (Related Pathway(s): Atrial fibrillation: Anticoagulation for adults with atrial fibrillation.)

Our approach to deciding whether to prescribe anticoagulant therapy for patients with AF (without severe or clinically significant rheumatic mitral stenosis [mitral valve area ≤1.5 cm2], a bioprosthetic valve [surgical or bioprosthetic] within the first three to six months after implantation, or a mechanical valve) is as follows:

For a CHA2DS2-VASc score ≥2 in males or ≥3 in females (calculator 1) (table 1), we recommend chronic OAC.

For a CHA2DS2-VASc score of 1 in males and 2 in females (calculator 1) (table 1), the specific nonsex risk factor present and the documented burden of AF influences decision making:

-For patients with CHA2DS2-VASc score of 1 in males and 2 in females based on age 65 to 74 years, we recommend chronic OAC. Age 65 to 74 years is a stronger risk factor than the other factors conferring one CHA2DS2-VASc score point [1].

-For patients with other risk factors, the decision to anticoagulate is based upon the specific nonsex risk factor and the burden of AF. For patients with very low burden of AF (eg, AF that is well documented as limited to an isolated episode that may have been due to a reversible cause such as recent surgery, heavy alcohol ingestion, or sleep deprivation), it may be reasonable to forgo chronic OAC and institute close surveillance for recurrent AF, although it may not be possible to reliably estimate AF burden from surveying symptoms or infrequent monitoring. The frequency and duration of AF episodes vary widely over time and episodes are often asymptomatic. (See "Atrial fibrillation in patients undergoing noncardiac surgery", section on 'Anticoagulation after surgery' and "Atrial fibrillation and flutter after cardiac surgery", section on 'Anticoagulation'.)

For patients with a CHA2DS2-VASc of 0 in males or 1 in females (calculator 1) (table 1), we suggest against anticoagulant therapy. Patient values and preferences may impact the decision. For example, a patient who is particularly stroke averse and is not at increased risk for bleeding (see 'Bleeding risk' below) may reasonably choose anticoagulation, particularly if the patient is a candidate for treatment with a direct oral anticoagulant (DOAC).

For all potential candidates for OAC, bleeding risk and related possible contraindications to OAC should be reviewed (table 2 and table 3). The appropriate use of bleeding risk assessment is to draw attention to modifiable bleeding risk factors that can be mitigated, and to flag patients with high bleeding risk for early review and follow-up and to identify potential candidates for left atrial appendage occlusion [2-6]. (See 'Bleeding risk' below and "Management of warfarin-associated bleeding or supratherapeutic INR", section on 'Mitigating bleeding risk' and "Risks and prevention of bleeding with oral anticoagulants", section on 'Risk factors for bleeding'.)

Effects of anticoagulation — In identifying which patients with AF are likely to benefit from OAC, the relative risk reduction in thromboembolism with OAC identified in randomized trials (see 'General efficacy' below) is combined with estimates of baseline risk using the CHA2DS2-VASc score to estimate the expected absolute risk reduction from OAC (see 'CHA2DS2-VASc score' below). The estimated absolute risk reduction for thromboembolic events is weighed against the estimated increase in absolute risk of intracranial hemorrhage (ICH) and other major bleeding complications. (See 'Bleeding risk' below.)

General efficacy — For patients with AF, randomized trials have shown that therapeutic OAC (vitamin K antagonist [VKA] or DOAC) reduces the risk of ischemic stroke and other embolic events by approximately two-thirds compared with placebo irrespective of baseline risk (figure 1) [7-17].

A meta-analysis included six randomized trials comparing VKA (warfarin) with placebo or no treatment in a total of 2900 participants with AF (mean age at entry 69 years, 20 percent with prior stroke or transient ischemic attack [TIA]) [14]. The overall rate of stroke was 2.2 percent/patient year in the warfarin group and 6.0 percent/patient year in the control group (relative risk reduction 0.64; 95% CI 0.49-0.74). The absolute risk reduction was 2.7 percent/year for primary prevention and 8.4 percent/year for secondary prevention. With warfarin therapy, all-cause mortality was reduced by 1.6 percent/year (relative risk reduction 0.26; 95% CI 0.03-0.43).

While most of the evidence comparing OAC with placebo in patients involved treatment with VKA, a trial comparing edoxaban 15 mg daily with placebo in patients with AF ≥80 years old with low body weight found a similar relative reduction in risk of stroke or systemic embolism (2.3 versus 6.7 percent/year; hazard ratio 0.34, 95% CI 0.19-0.61) [18]. The possible implications of this study for edoxaban dose are discussed separately. (See "Atrial fibrillation in adults: Use of oral anticoagulants" and "Atrial fibrillation in adults: Use of oral anticoagulants", section on 'DOACs'.)

CHA2DS2-VASc score

Use — We use the CHA2DS2-VASc score (calculator 1) to estimate thromboembolic risk in patients with AF, while recognizing its limitations (see 'Potential alternatives' below and 'Limitations' below). This estimation of baseline thromboembolic risk is combined with the above information on relative risk reduction (see 'General efficacy' above) to estimate the expected absolute risk reduction.

The annual risk of ischemic stroke in untreated patients is estimated to be 0.2, 0.6, and 2.2 percent for those with CHA2DS2-VASc scores of 0, 1, and 2 (table 1) [19]. However, stroke rates have varied substantially among studies, which may be due to differences in study populations and methodologies [2,20-24]. As an example, studies examining ischemic stroke rates in patients with a single risk factor have identified risks of <1 to 2.7 percent/year [25-27].

Among patients with AF, ischemic stroke is the dominant type of thromboembolic event. As an example, in a study including data on 39,973 participants in four randomized trials of anticoagulation, the incidence of nonstroke systemic embolic events (SEEs) was 0.23/100 person-years, and the incidence of cerebral embolism was 1.92/100 person-years [28]. Among those with SEEs, 58 percent occurred in the lower extremities, 31 percent in the visceral-mesenteric system, and 11 percent in the upper extremities.

Among patients with AF treated with OAC, annual stroke risk is lowered by approximately two-thirds to <0.1, 0.2, and 0.6 percent, respectively. In addition to the lowering of stroke risk, there is evidence that warfarin, compared with no anticoagulant therapy, leads to less severe stroke episodes and lower 30-day stroke mortality [14,29].

The annual risk of intracranial bleeding with warfarin is 0.2, 0.3, and 0.5 percent, respectively. The risk of ICH with DOAC is approximately half of that with VKA (table 4). (See "Atrial fibrillation in adults: Use of oral anticoagulants", section on 'Choice of anticoagulant'.)

Among adults with AF, females have a modestly higher risk of thromboembolism than males, but female sex is associated with increased risk primarily in patients with at least two CHA2DS2-VASc score non-sex risk score points [1,30]. Thus, we focus on non-sex risk factors when deciding whether OAC is indicated.

For CHA2DS2-VASc score ≥2 in males or ≥3 in females (when the risk score points are from two or more non-sex risk factors), the benefit from OAC generally exceeds the risks of severe bleeding [19,31-33].

For CHA2DS2-VASc score of 1 in males or 2 in females (one non-sex risk factor with a value of 1), the risk of thromboembolism varies depending upon the non-sex risk factor [1]. Among the risk factors with a one-point value, age 65 to 74 years and the presence of heart failure have the greatest effect on thromboembolic risk [1], and OAC is recommended in patients with any of these risk factors.

For CHA2DS2- VASc score of 0 in males or 1 in females (zero nonsex risk factors), the thromboembolic risk is low [27], so no OAC is suggested. (See 'Approach to deciding whether to anticoagulate' above.)

The warfarin versus placebo or aspirin trials were reported in the early 1990s, raising concerns that the findings may not be applicable to contemporary clinical practice [31,34,35]. Studies evaluating more contemporary data have found that the absolute risk of stroke in untreated patients has fallen from approximately 8 percent/year to 4 or 5 percent/year (table 1), but the relative risk reduction attributable to anticoagulant therapy is in the same range as earlier studies [36,37]. A two-thirds risk reduction in thromboembolism using the more contemporary lower absolute risks is clinically important for patients with two or more nonsex risk factors and for selected patients with one nonsex risk factor.

Comparisons of the effects of VKA and DOAC are presented separately. (See "Atrial fibrillation in adults: Use of oral anticoagulants".)

Potential alternatives — A variety of risk scores, imaging methods, and biomarkers have been studied for their potential predictive value for thromboembolic risk in patients with AF [38].

The CHA2DS2-VASc score has been compared with potential alternatives including the CHADS2 and ATRIA risk scores (table 1 and table 5). The clinical utility of a risk score for individuals with AF hinges primarily on its accuracy in identifying those at lowest risk for thromboembolism, as anticoagulation is generally recommended for individuals with all but the lowest level of risk. Systematic reviews suggest that the CHA2DS2-VASc score generally performs better than the CHADS2 and ATRIA scores in identifying low-risk patients, although there have been some discrepant results for comparisons of CHA2DS2-VASc and ATRIA [38]. However, all these risk scores are subject to the limitations discussed below. (See 'Limitations' below.)

A potential alternative to the risk score approach is to calculate the risk for each patient based upon risk factors including age as a continuous variable using the Calculator of Absolute Stroke Risk (CARS) [1].

For patients with AF, there is no established role for routine cardiac imaging to assess thromboembolic risk. Transesophageal echocardiography (TEE) is used in patients with AF primarily to evaluate left and right atrial appendage anatomy/function to identify individuals who are free of atrial thrombi and are therefore candidates for early cardioversion (see "Prevention of embolization prior to and after restoration of sinus rhythm in atrial fibrillation"). Thromboembolic risk is associated with cardiac imaging findings, including evidence of left atrial thrombus (generally assessed by TEE; less commonly assessed by cardiovascular magnetic resonance [CMR] or cardiac computed tomography [CCT]) and depressed left ventricular ejection fraction (which can be assessed by transthoracic echocardiography, TEE, CMR, CCT, or nuclear methods) [39]. However, imaging findings have not been shown to improve risk stratification in patients with AF [2].

Limitations — Risk scores to estimate thromboembolic risk in patients with AF have limited predictive value when applied to individual patients.

One limitation is that risk scores utilize point systems that do not reflect differences in risk among included risk factors. Risk factors assigned equal point values are associated with substantially different risks, as illustrated by the following examples for the CHA2DS2-VASc score (table 1) [1]:

Age 65 to 74 years is associated with substantially greater stroke risk than other risk factors assigned one point.

A history of prior stroke, TIA, or thromboembolic event is assigned two points, but the risk associated with this risk factor is more than five times the risk associated with risk factors assigned one point.

The continuous risk of age is lumped into categories, so that ages 65 years and 74 years each confer one point, despite the much higher actual risk associated with the older age.

Another limitation is that the event rates observed in populations used to generate risk score may differ from those occurring in different clinical settings (eg, community versus hospitalized) and patient populations with differing risk profiles.

Also, some clinical features or conditions may impact the risk of thromboembolism but are not included in risk models; these include the duration or frequency of episodes of paroxysmal AF and the presence of conditions such as chronic kidney disease and elevated troponin level. Prediabetes has also been implicated as a possible risk factor for stroke in patients with AF [40]. The potential role of troponin measurement in the assessment of the risk of embolization in patients with AF is discussed separately. (See 'Chronic kidney disease' below and "Elevated cardiac troponin concentration in the absence of an acute coronary syndrome", section on 'Atrial fibrillation'.)

Bleeding risk — When OAC is considered, the major safety concern is the increased risk of bleeding, especially major bleeding, which includes events that require hospitalization, transfusion, or surgery, or that involve particularly sensitive anatomic locations. Thus, bleeding risk and related contraindications to OAC should be reviewed (table 2).

A systematic review comparing various bleeding risk scores in patients with AF found that the HAS-BLED risk score (table 3) was the best predictor of bleeding risk [2], although all bleeding risk scores provide imprecise estimates for individual patients, do not provide estimates for specific types of major bleeds, and are based upon bleeding risk with warfarin. Two more recent studies confirmed the efficacy of the HAS-BLED score was comparable to or better than ORBIT score in patients treated with DOACs [41,42]. Among patients with AF, the three most important predictors of major bleeding (including ICH) are overanticoagulation with warfarin (defined as an international normalized ratio greater than 3.0), prior stroke, and older patient age [31,43-45]. (See "Risks and prevention of bleeding with oral anticoagulants".)

The risk of bleeding was evaluated in a cohort of over 16,000 patients diagnosed with AF between 2005 and 2010 [37]. The incidence of major bleeding with current, recent, past, or no VKA (warfarin) exposure was 3.8, 4.5, 2.7, and 2.9/100 patient-years, respectively. However, major bleeding includes ICH and extracranial bleeding, particularly gastrointestinal bleeding. ICH is the most serious bleeding complication, since the likelihood of mortality or subsequent major disability is substantially higher than with bleeding at other sites [46]. In this study and others, the annual risk of ICH in patients with AF who are not anticoagulated is estimated to be 0.2 percent/year; that risk approximately doubles with OAC with VKA [34,37]. Randomized trials have shown that the risk of ICH with DOAC (both direct thrombin and factor Xa inhibitors) is approximately half of that with VKA (table 4). (See "Atrial fibrillation in adults: Use of oral anticoagulants", section on 'Choice of anticoagulant'.)

Given differences in morbidity associated with different types of bleeding, we think most patients would weigh the reduction in risk of ischemic stroke primarily against the increase in risk of ICH, with less weight given to the risk of gastrointestinal bleed or other less serious bleeding. While the incremental absolute risk of ICH with VKA (approximately 0.2 percent/year) is not trivial, it is substantially less than the expected absolute reduction in risk of ischemic stroke from OAC for most patients with AF and two or more nonsex CHA2DS2-VASc risk factors.

One problem with the bleeding risk scores is that they were developed from studies that included bleeds of differing severity. While any bleed can lead to death or severe disability, most do not; the major exception is ICH. The morbidity associated with ICH is similar to that for ischemic stroke, while the morbidity associated with gastrointestinal bleeding is generally not as severe. (See "Risks and prevention of bleeding with oral anticoagulants", section on 'Intracranial'.)

For patients in the following clinical settings, the bleeding risk is significantly higher:

Thrombocytopenia or known coagulation defect associated with bleeding

Active bleeding or recent surgery with a concern for ongoing bleeding

Prior severe bleeding (including ICH) while on an oral anticoagulant

Aortic dissection

Malignant hypertension

Combined use of anticoagulant and antiplatelet (including regular use of nonsteroidal antiinflammatory) agents

SPECIFIC PATIENT GROUPS

Patients with valvular heart disease — For patients with valvular heart disease (excluding those with rheumatic mitral stenosis that is severe or clinically significant [mitral valve area ≤1.5 cm2], a bioprosthetic valve [surgical or transcatheter] within the first three to six months after implantation, or a mechanical heart valve), the above general approach to deciding on oral anticoagulation (OAC) applies, although the evidence in patients with severe native valve disease is more limited than for the general population of patients with AF [47]. (See 'Approach to deciding whether to anticoagulate' above.)

Approaches to antithrombotic therapy (including anticoagulation) in patients with AF with specific valve conditions are discussed separately:

Rheumatic mitral stenosis that is severe or clinically significant (mitral valve area ≤1.5 cm2). (See "Rheumatic mitral stenosis: Overview of management", section on 'Prevention of thromboembolism'.)

Mechanical heart valve. (See "Antithrombotic therapy for mechanical heart valves".)

Surgically implanted bioprosthetic valve. (See "Antithrombotic therapy for mechanical heart valves".)

Transcatheter bioprosthetic valve. (See "Transcatheter aortic valve implantation: Antithrombotic therapy", section on 'General approach'.)

AF type and management

Paroxysmal AF — Our approach to deciding whether to anticoagulate is generally similar for patients with paroxysmal AF (PAF; with or without symptoms) as for persistent, or permanent, AF, as described above (see 'Decision-making based upon risk assessment' above). However, the burden of AF (duration and frequency of episodes) is a factor for decision-making for selected patients in whom the balance of benefit versus risk of anticoagulation is uncertain, recognizing that it may not be possible to accurately estimate AF burden except in patients with cardiac implantable electronic devices that can measure AF burden. We consider the burden of AF in decision-making for patients aged <65 years and who have one nonsex CHA2DS2-VASc risk factor. On the other hand, patients with AF with past history of embolic stroke are at high risk for a recurrent thromboembolic event, so the burden of AF would generally not impact the decision to anticoagulate. (See 'Decision-making based upon risk assessment' above.)

As discussed separately, the risk of thromboembolism in patients with PAF appears to be lower than in patients with persistent AF, and thromboembolic risk is higher in those with greater AF burden (percentage of time in AF). (See "Paroxysmal atrial fibrillation", section on 'Risk of embolization'.)

There are no definitive data to establish a threshold duration of AF episodes for the initiation of anticoagulant therapy. Some of our experts recommend a single threshold for duration of AF of 30 seconds, and others use a threshold as long as 24 hours [48]. Those experts who do not routinely anticoagulate patients with shorter-duration AF believe that the benefit is small and potentially outweighed by the bleeding risk. However, the AF burden is likely to vary over time, so a patient with 30 seconds of AF in one monitoring period may well have 30 hours of AF in the next monitoring period. While a large proportion of patients with short episodes of AF will go on to experience longer episodes, it is also true that the reverse occurs in a sizable percentage of patients experiencing long episodes of AF [49]. Also, the extent to which thromboembolic risk may continue during periods of sinus rhythm is uncertain. (See "Paroxysmal atrial fibrillation", section on 'Risk of embolization'.)

Device-detected AF — Similar considerations apply to patients with device-detected (subclinical) AF as to patients with PAF, with the understanding that many patients with subclinical AF have very low AF burden.

Device-detected AF (also known as subclinical AF or atrial high-rate episodes [AHRE]) is commonly identified in patients with a pacemaker, implantable cardioverter-defibrillator, or implanted cardiac monitor. The effects of anticoagulation for device-detected AF were assessed by a meta-analysis of two randomized controlled trials [50]: a trial enrolling 2536 individuals (mean age 77.5 years; median CHA2DS2-VASc score 4; prior stroke, systemic embolism, or transient ischemic attack [TIA] 10 percent) with AHREs (median duration 2.8 hours; interquartile range [IQR] 0.8-9.2 hours) that compared edoxaban with placebo or aspirin 100 mg [51] and a trial enrolling 4012 individuals (mean age 76.8 years; mean CHA2DS2-VASc score 3.9; prior stroke, systemic embolism, or TIA 9 percent) with subclinical AF (median duration 1.5 hours; IQR 0.2-5 hours) that compared apixaban with aspirin 81 mg [52].

The stroke rates were low in both arms of both trials [50]. In the trial comparing edoxaban with placebo/aspirin, ischemic stroke rates were 0.9 and 1.1 percent per patient-year [51]. In the trial comparing apixaban with aspirin, ischemic stroke rates were 0.64 and 1.02 percent per patient-year [52].

Meta-analysis found that oral anticoagulation reduced ischemic stroke (relative risk [RR] 0.68, 95% CI 0.50-0.92) but did not reduce all-cause mortality (RR 1.08, 95% CI 0.96-1.21). Oral anticoagulation increased major bleeding (RR 1.62, 95% CI 1.05-2.5) [50].

Rhythm versus rate control — For patients with AF, the process of deciding whether to anticoagulate is generally the same regardless of the choice between rhythm control or rate control strategies. As discussed separately, the risk of thromboembolism is not reduced by clinical maintenance of sinus rhythm. (See "Management of atrial fibrillation: Rhythm control versus rate control", section on 'Thromboembolic risk'.)

AF after surgery — Approaches to OAC in patients with AF after cardiac surgery and after noncardiac surgery are discussed separately. (See "Atrial fibrillation and flutter after cardiac surgery", section on 'Our approach to postoperative anticoagulation' and "Atrial fibrillation in patients undergoing noncardiac surgery", section on 'Anticoagulation after surgery'.)

Older adults — For older adults, we follow the general approach described above, including careful assessment the relative benefits and risks of OAC (see 'Decision-making based upon risk assessment' above). The approach to chronic kidney disease is discussed below. (See 'Chronic kidney disease' below.)

In patients with documented frequent falls but without prior trauma (eg, fracture, subdural), we weight the risks and benefits of OAC versus left atrial appendage occlusion. In this clinical setting, we often recommend OAC and work to reduce the risk of falls. The risk of falls leading to subdural hematomas is increased in older adult patients taking oral anticoagulants independent of the agent chosen. (See "Risks and prevention of bleeding with oral anticoagulants", section on 'Age, race, and sex' and "Atrial fibrillation: Left atrial appendage occlusion".)

A Taiwanese database study compared 15,756 older (≥90 years of age) adults with AF (11,064 receiving no antithrombotic therapy, 4075 receiving antiplatelet therapy, and 617 on warfarin) with 14,658 older adult patients without AF and without antithrombotic therapy [53]:

Patients with AF had a greater risk of ischemic stroke (5.75 versus 3.00 percent/year; hazard ratio [HR] 1.93, 95% CI 1.74-2.14) and a similar risk of intracranial hemorrhage (ICH; 0.97 versus 0.54 percent/year; HR 0.85, 95% CI 0.66-1.09) compared with those without AF.

Among patients with AF, warfarin use was associated with a lower stroke risk (3.83 versus 5.75 percent/year; HR 0.69, 95% CI 0.49-0.96) compared with no antithrombotic therapy. There was a nominal but nonsignificant increase in risk of ICH (HR 1.26, 95% CI 0.70-2.25).

In a second, later cohort of patients ≥90 years of age with AF, 768 patients treated with warfarin were compared with 978 patients treated with a direct oral anticoagulant (DOAC) [53]. DOACs were associated with a lower risk of ICH compared with warfarin (0.42 versus 1.63 percent/year; HR 0.32, 95% CI 0.10-0.97) and similar rate of ischemic stroke (4.07 versus 4.59 percent/year; HR 1.16; 95% CI 0.61–2.22). (See "Atrial fibrillation in adults: Use of oral anticoagulants", section on 'Older adults'.)

Potential use of reduced-dose DOAC (edoxaban) in selected older adults with AF with low body weight is discussed separately. (See "Atrial fibrillation in adults: Use of oral anticoagulants", section on 'DOACs'.)

Chronic kidney disease — For most patients with AF and chronic kidney disease (CKD), we follow the general approach to selection of candidates for OAC described above (see 'Approach to deciding whether to anticoagulate' above). However, some of our authors consider anticoagulation for the very uncommon CKD patient with a CHA2DS2-VASc score of 0 in males or 1 in females.

For patients with CKD and AF, the following is our approach for deciding whether to anticoagulate (figure 2):

Stages 2, 3, and 4 and 5 (not on dialysis) – For patients with estimated glomerular filtration rate (eGFR) of 15 to 89 mL/min/1.73 m2, our approach is similar to the general approach described above (see 'Decision-making based upon risk assessment' above), although there are very limited data for patients with end-stage kidney disease. Individualized risk assessment is performed to carefully weigh the benefits and risks of anticoagulation, with special attention to the bleeding risk associated with CKD. (See "Overview of the management of chronic kidney disease in adults", section on 'Uremic bleeding'.)

Stage 5 on dialysis – Among patients with end-stage kidney disease on dialysis, we anticoagulate some higher-risk individuals (based on the CHA2DS2-VASc score) after shared decision-making and discussion of risks and benefits between the clinician and the patient.

However, it is reasonable to not anticoagulate the following groups of individuals with AF and eGFR <30 mL/min (stages 4 and 5) given our uncertainty of the benefit-to-risk ratio for antithrombotic therapy in these patients:

Patients with high frailty

Patients with prior life-threatening bleeding or recurrent bleeding

Patients with poorly controlled hypertension

AF is common in patients with CKD [54-59], with prevalence between 8 and 35 percent in patients on hemodialysis and approximately 7 percent in patients undergoing peritoneal dialysis [60-62]. This rate is significantly higher than in the general population [63-66]. Rates are even higher in studies which used prolonged/continuous monitoring for identifying AF (figure 3) [54,55,67]. CKD significantly increases thromboembolic risk above baseline and is also associated with increased risk of bleeding [68-71]. Studies assessing the independent predictive value of presence of CKD for thromboembolic risk beyond the CHA2DS2-VASc score have yielded mixed results [68,72,73]. The thromboembolic risk associated with CKD may be due to alterations in the normal hemostatic mechanisms. The increased bleeding risk, particularly from the gastrointestinal tract, is due to pathophysiologic mechanisms including impairment of normal platelet function secondary to factors such as uremic toxins, abnormal platelet arachidonic acid metabolism, altered von Willebrand factor, and reduction in intracellular adenosine diphosphate and serotonin, as well as an increase in the frequency of the need for invasive procedures [63]. (See "Uremic platelet dysfunction".)

The evidence to support OAC (vitamin K antagonist [VKA] or DOAC) is less robust in individuals with creatinine clearance <30 mL/min, as many such patients were excluded from the important randomized trials [74]. However, we believe that the benefit outweighs the risk in most cases.

The efficacy and safety of warfarin in patients with AF and CKD have been evaluated in observational studies which have come to differing conclusions [69,75-80]. A 2020 meta-analysis of 15 studies (with a total of 47,480 patients with AF and end-stage renal disease) found no difference in the risk of ischemic stroke (HR 0.96, 95% CI 0.82-1.13), a higher risk of hemorrhage stroke (HR 1.46, 95% CI 1.05-2.04), and no significant difference in mortality (HR 0.95, 95% CI 0.83-1.09) or major bleeding (HR 1.20, 95% CI 0.99-1.47) in comparing warfarin users with those not taking warfarin [81]. Many of the observational cohorts did not evaluate the quality of the OAC with warfarin, such as the time in the therapeutic range (TTR). This may be relevant since evidence suggests that higher TTR is associated with better outcomes. (See "Warfarin and other VKAs: Dosing and adverse effects", section on 'Monitoring (PT/INR)'.)

Hyperthyroidism — The role of anticoagulant therapy is less well defined in patients in whom the underlying disease associated with AF can be corrected, as in hyperthyroidism. (See "Epidemiology, risk factors, and prevention of atrial fibrillation" and "Cardiovascular effects of hyperthyroidism", section on 'Atrial fibrillation'.)

For patients with AF attributable to hyperthyroidism, we follow the general approach described above for identifying candidates for OAC. (See 'Approach to deciding whether to anticoagulate' above.)

After successful treatment of the disorder, and after documentation that AF has not been present for at least three months, most of our experts suggest discontinuing anticoagulant treatment with periodic reassessment of the patient for recurrence of AF. We consider the absence of symptoms or signs of AF and two-week continuous monitoring showing no AF as adequate documentation. Some experts prefer additional documentation. However, some of our experts make a decision about continuing anticoagulant therapy based on the CHA2DS2-VASc score independent of monitored rhythm in these patients.

Hypertrophic cardiomyopathy — The role of OAC in patients with hypertrophic cardiomyopathy and AF is discussed separately. (See "Hypertrophic cardiomyopathy in adults: Supraventricular tachycardias including atrial fibrillation", section on 'Long-term management'.)

Patients with cancer on chemotherapy — Several chemotherapy drugs have been associated with AF and atrial flutter. Depending on severity, dose reduction or discontinuation of the offending chemotherapy agent may be indicated. (See "Cardiotoxicity of cancer chemotherapy agents other than anthracyclines, HER2-targeted agents, and fluoropyrimidines".)

For most patients with AF and cancer who are on chemotherapy, we follow the general approach to selection of candidates for OACs described above. (See 'Approach to deciding whether to anticoagulate' above.)

For patients who have AF in the setting of chemotherapy-related thrombocytopenia, OACs may require a dose reduction in order to prevent bleeding. (See "Anticoagulation in individuals with thrombocytopenia", section on 'Atrial fibrillation'.)

ALTERNATIVES TO ANTICOAGULATION

Left atrial appendage occlusion — As discussed separately, left atrial appendage occlusion is the primary alternative for patients with AF (excluding those with severe or clinically significant rheumatic stenosis, a bioprosthetic valve [surgical or bioprosthetic] within the first three to six months after implantation, or a mechanical valve) who have an indication for anticoagulation but have a contraindication for long-term anticoagulation. (See 'Decision-making based upon risk assessment' above and "Atrial fibrillation: Left atrial appendage occlusion".)

Pharmacologic agents — For patients with AF, no other antithrombotic regimen is an effective and safe alternative to standard therapeutic oral anticoagulation (OAC). In this setting, other antithrombotic regimens are less effective in lowering thromboembolic risk than standard therapeutic OAC and some antithrombotic regimens entail a bleeding risk similar to or greater than standard therapeutic OAC:

Aspirin plus clopidogrel – Dual antiplatelet therapy is preferred to aspirin alone in the occasional high-risk patient with AF who cannot be treated with any OAC for a reason other than risk of bleeding. Given the availability of the direct oral anticoagulant (DOAC) agents as alternatives to vitamin K antagonists (VKAs), this situation should be extremely uncommon. One possible example is a patient with contraindications to DOAC agents who cannot receive effective international normalized ratio (INR) monitoring for VKA. Of note, dual antiplatelet therapy and OAC have similar bleeding risks. Thus, a patient who would not be a candidate for OAC because of bleeding risk is also not a candidate for dual antiplatelet therapy.

In patients with AF, dual antiplatelet therapy (with aspirin plus clopidogrel) reduces the risk of thromboembolism compared with aspirin monotherapy but offers less protection against thromboembolism than OAC (with VKA or DOAC).

The safety and efficacy of dual antiplatelet therapy in patients with AF were investigated in the ACTIVE W and ACTIVE A trials. All patients in the two trials had AF and one or more risk factors for stroke. The primary endpoint in both trials was a composite outcome (the first occurrence of stroke, systemic [non-central nervous system] embolization, myocardial infarction, or vascular death). The ACTIVE W trial included 6706 patients who were randomly assigned to combined therapy with clopidogrel (75 mg/day) and aspirin (75 to 100 mg/day) or to OAC with a VKA (target INR 2.0 to 3.0) [82]. The trial was stopped at an interim analysis after a median follow-up of 1.3 years because VKA lowered the annual rate of the primary endpoint compared with combined antiplatelet therapy (3.9 versus 5.6 percent; relative risk [RR] 0.69, 95% CI 0.57-0.85).

The ACTIVE A trial included 7554 patients with AF who were not candidates for warfarin OAC and were randomly assigned to combined therapy with clopidogrel (75 mg/day) and aspirin (75 to 100 mg/day) or to aspirin alone at the same dose [83]. After a median follow-up period of 3.6 years, patients treated with clopidogrel plus aspirin had a significantly lower annual rate of the primary combined endpoint (6.8 versus 7.8 percent; RR 0.89, 95% CI 0.81-0.98), which was primarily driven by a reduction in stroke (2.4 versus 3.3 percent; RR 0.72, 95% CI 0.62-0.83). On the other hand, dual antiplatelet therapy resulted in a higher rate of major bleeding (2.0 versus 1.3 percent/year; RR 1.57, 95% CI 1.29-1.92).

Aspirin monotherapyAspirin (or other antiplatelet agent) is not an effective therapy for preventing thromboembolic events in patients with AF. In patients with AF, some but not all meta-analyses of clinical trials comparing aspirin with placebo have found that aspirin reduced the risk of stroke and systemic embolism (table 6) [14,38,84]. In contrast, clinical trials have demonstrated that OAC (with VKA or DOAC) lowers the risk of thromboembolism compared with aspirin (table 6) [9,14-17,85-87].

Aspirin plus low-dose warfarin – In contrast to therapeutic adjusted-dose warfarin (target INR 2.0 to 3.0), low-dose warfarin (1.25 mg/day or target INR between 1.2 and 1.5) in combination with aspirin (300 to 325 mg/day) should not be used to reduce stroke risk in patients with nonvalvular AF [17,88,89]. In the SPAF-III trial of 1044 patients with AF who were at high risk for embolism, low-dose warfarin plus aspirin had a much higher rate of ischemic stroke and systemic embolism than therapeutic adjusted-dose warfarin (figure 4A-B) [88].

Aspirin plus full-dose warfarin – Limited available data suggest that there is no benefit from adding aspirin to therapeutic OAC in patients with AF. In a post-hoc analysis of the SPORTIF trials in patients with AF, among patients taking aspirin plus warfarin (or aspirin plus the factor Xa inhibitor ximelagatran) experienced similar rates of stroke and systemic embolism as those taking warfarin alone (or ximelagatran alone) [90]. The risk of major bleeding was higher with aspirin plus warfarin compared with warfarin alone (3.9 versus 2.3 percent/year).

The management of antithrombotic therapy for patients with AF treated with OAC who have a concurrent indication for antiplatelet therapy is discussed separately. (See "Atrial fibrillation in adults: Use of oral anticoagulants", section on 'Concomitant antiplatelet therapy'.)

RECOMMENDATIONS OF OTHERS — Recommendations for choosing which patients with atrial fibrillation should be anticoagulated are available from the American Heart Association/American College of Cardiology/Heart Rhythm Society, the European Society of Cardiology, and the American College of Chest Physicians [38,91-93]. In general, we agree with relevant recommendations made in these guidelines.

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Atrial fibrillation" and "Society guideline links: Arrhythmias in adults" and "Society guideline links: Anticoagulation".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, “The Basics” and “Beyond the Basics.” The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on “patient info” and the keyword(s) of interest.)

Basics topics (see "Patient education: Atrial fibrillation (The Basics)" and "Patient education: Medicines for atrial fibrillation (The Basics)" and "Patient education: Choosing an oral medicine for blood clots (The Basics)" and "Patient education: Taking oral medicines for blood clots (The Basics)")

Beyond the Basics topics (see "Patient education: Atrial fibrillation (Beyond the Basics)" and "Patient education: Warfarin (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

Role of oral anticoagulation (OAC) in atrial fibrillation (AF) – In patients with AF, OAC reduces the risk of thromboembolism by approximately two-thirds across clinical risk factor profiles but also entails an increased risk of major bleeding.

Deciding whether to anticoagulate – For each patient, their estimated absolute risk reduction for thromboembolic events is weighed against their estimated increase in absolute risk of intracranial hemorrhage and other life-threatening or severely debilitating bleeding complications. (See 'Approach to deciding whether to anticoagulate' above.)

CHA2DS2-VASc risk score – Our approach to deciding whether to prescribe anticoagulant therapy for patients with AF (excluding those with rheumatic mitral stenosis that is severe or clinically significant [mitral valve area ≤1.5 cm2], a bioprosthetic valve [surgical or transcatheter] within the first three to six months after implantation, or a mechanical heart valve) is as follows (see 'Approach to deciding whether to anticoagulate' above):

For a CHA2DS2-VASc score ≥2 in males or ≥3 in females (calculator 1) (table 1), we recommend chronic OAC (Grade 1A).

For a CHA2DS2-VASc score of 1 in males and 2 in females (calculator 1) (table 1):

-For patients with CHA2DS2-VASc score of 1 in males and 2 in females based on age 65 to 74 years, we recommend chronic OAC (Grade 1A). Age 65 to 74 years is a stronger risk factor than the other factors conferring one CHA2DS2-VASc score point.

-For patients with other risk factors, the decision to anticoagulate is based upon the specific nonsex risk factor and the burden of AF. For patients with very low burden of AF (eg, AF that is well documented as limited to an isolated episode that may have been due to a reversible cause such as recent surgery, heavy alcohol ingestion, or sleep deprivation), it may be reasonable to forgo chronic OAC and institute close surveillance for recurrent AF, although it may not be possible to reliably estimate AF burden from surveying symptoms or infrequent monitoring. (See "Atrial fibrillation in patients undergoing noncardiac surgery", section on 'Anticoagulation after surgery' and "Atrial fibrillation and flutter after cardiac surgery", section on 'Anticoagulation'.)

For patients with a CHA2DS2-VASc of 0 in males or 1 in females (calculator 1) (table 1), we suggest against OAC (Grade 2C). Patient values and preferences may impact the decision. For example, a patient who is particularly stroke averse and is not at increased risk for bleeding (see 'Bleeding risk' above) may reasonably choose anticoagulation, particularly if the patient is a candidate for treatment with a direct oral anticoagulant (DOAC).

Bleeding risk – For all potential candidates for OAC, bleeding risk and related possible contraindications to OAC should be reviewed (table 2 and table 3). (See 'Bleeding risk' above.)

The appropriate use of bleeding risk assessment is to draw attention to modifiable bleeding risk factors that can be mitigated to flag high-bleeding-risk patients for early review and follow-up. (See "Risks and prevention of bleeding with oral anticoagulants", section on 'Bleeding risk scores' and "Management of warfarin-associated bleeding or supratherapeutic INR", section on 'Mitigating bleeding risk'.)

Specific patient groups

Paroxysmal AF – Our approach to deciding whether to anticoagulate is generally similar for patients with paroxysmal AF (PAF; with or without symptoms) as for persistent, or permanent, AF, as described above (see 'Decision-making based upon risk assessment' above). However, the burden of AF (duration and frequency of episodes) is a factor for decision-making for selected patients in whom the balance of benefit versus risk of anticoagulation is uncertain. (See 'Paroxysmal AF' above.)

Similar considerations apply to patients with device-detected (subclinical) AF, with the understanding that many patients with subclinical AF have very low AF burden. (See 'Device-detected AF' above.)

Concurrent conditions – Our approach to OAC for patients with AF who are older, have chronic kidney disease, hyperthyroidism, and hypertrophic cardiomyopathy can sometimes differ for patients who are younger or do not have these conditions. (See 'Specific patient groups' above.)

Contraindication to OAC – For patients with AF (excluding those with severe or clinically significant rheumatic stenosis, a surgical bioprosthetic valve within the first three to six months after implantation, or a mechanical valve) with an indication for OAC but who have a contraindication for long-term OAC, the primary alternative is left atrial appendage occlusion. For such patients, no other antithrombotic regimen is an effective and safe alternative to standard therapeutic OAC. (See 'Alternatives to anticoagulation' above and "Atrial fibrillation: Left atrial appendage occlusion".)

  1. Lee CJ, Toft-Petersen AP, Ozenne B, et al. Assessing absolute stroke risk in patients with atrial fibrillation using a risk factor-based approach. Eur Heart J Cardiovasc Pharmacother 2021; 7:f3.
  2. Borre ED, Goode A, Raitz G, et al. Predicting Thromboembolic and Bleeding Event Risk in Patients with Non-Valvular Atrial Fibrillation: A Systematic Review. Thromb Haemost 2018; 118:2171.
  3. Lip GY, Lane DA. Bleeding risk assessment in atrial fibrillation: observations on the use and misuse of bleeding risk scores. J Thromb Haemost 2016; 14:1711.
  4. Lip GY, Lane DA. Assessing bleeding risk in atrial fibrillation with the HAS-BLED and ORBIT scores: clinical application requires focus on the reversible bleeding risk factors. Eur Heart J 2015; 36:3265.
  5. Guo Y, Lane DA, Chen Y, et al. Regular Bleeding Risk Assessment Associated with Reduction in Bleeding Outcomes: The mAFA-II Randomized Trial. Am J Med 2020; 133:1195.
  6. Fang MC, Go AS, Chang Y, et al. A new risk scheme to predict warfarin-associated hemorrhage: The ATRIA (Anticoagulation and Risk Factors in Atrial Fibrillation) Study. J Am Coll Cardiol 2011; 58:395.
  7. Boston Area Anticoagulation Trial for Atrial Fibrillation Investigators, Singer DE, Hughes RA, et al. The effect of low-dose warfarin on the risk of stroke in patients with nonrheumatic atrial fibrillation. N Engl J Med 1990; 323:1505.
  8. Stroke Prevention in Atrial Fibrillation Study. Final results. Circulation 1991; 84:527.
  9. Warfarin versus aspirin for prevention of thromboembolism in atrial fibrillation: Stroke Prevention in Atrial Fibrillation II Study. Lancet 1994; 343:687.
  10. Petersen P, Boysen G, Godtfredsen J, et al. Placebo-controlled, randomised trial of warfarin and aspirin for prevention of thromboembolic complications in chronic atrial fibrillation. The Copenhagen AFASAK study. Lancet 1989; 1:175.
  11. Ezekowitz MD, Bridgers SL, James KE, et al. Warfarin in the prevention of stroke associated with nonrheumatic atrial fibrillation. Veterans Affairs Stroke Prevention in Nonrheumatic Atrial Fibrillation Investigators. N Engl J Med 1992; 327:1406.
  12. Connolly SJ, Laupacis A, Gent M, et al. Canadian Atrial Fibrillation Anticoagulation (CAFA) Study. J Am Coll Cardiol 1991; 18:349.
  13. Risk factors for stroke and efficacy of antithrombotic therapy in atrial fibrillation. Analysis of pooled data from five randomized controlled trials. Arch Intern Med 1994; 154:1449.
  14. Hart RG, Pearce LA, Aguilar MI. Meta-analysis: antithrombotic therapy to prevent stroke in patients who have nonvalvular atrial fibrillation. Ann Intern Med 2007; 146:857.
  15. van Walraven C, Hart RG, Singer DE, et al. Oral anticoagulants vs aspirin in nonvalvular atrial fibrillation: an individual patient meta-analysis. JAMA 2002; 288:2441.
  16. Cooper NJ, Sutton AJ, Lu G, Khunti K. Mixed comparison of stroke prevention treatments in individuals with nonrheumatic atrial fibrillation. Arch Intern Med 2006; 166:1269.
  17. McNamara RL, Tamariz LJ, Segal JB, Bass EB. Management of atrial fibrillation: review of the evidence for the role of pharmacologic therapy, electrical cardioversion, and echocardiography. Ann Intern Med 2003; 139:1018.
  18. Okumura K, Akao M, Yoshida T, et al. Low-Dose Edoxaban in Very Elderly Patients with Atrial Fibrillation. N Engl J Med 2020; 383:1735.
  19. Friberg L, Rosenqvist M, Lip GY. Net clinical benefit of warfarin in patients with atrial fibrillation: a report from the Swedish atrial fibrillation cohort study. Circulation 2012; 125:2298.
  20. Nielsen PB, Chao TF. The risks of risk scores for stroke risk assessment in atrial fibrillation. Thromb Haemost 2015; 113:1170.
  21. Nielsen PB, Larsen TB, Skjøth F, et al. Stroke and thromboembolic event rates in atrial fibrillation according to different guideline treatment thresholds: A nationwide cohort study. Sci Rep 2016; 6:27410.
  22. Quinn GR, Severdija ON, Chang Y, Singer DE. Wide Variation in Reported Rates of Stroke Across Cohorts of Patients With Atrial Fibrillation. Circulation 2017; 135:208.
  23. Quinn GR, Severdija ON, Chang Y, et al. Methodologic Differences Across Studies of Patients With Atrial Fibrillation Lead to Varying Estimates of Stroke Risk. J Am Heart Assoc 2018; 7.
  24. Shah SJ, Eckman MH, Aspberg S, et al. Effect of Variation in Published Stroke Rates on the Net Clinical Benefit of Anticoagulation for Atrial Fibrillation. Ann Intern Med 2018; 169:517.
  25. Friberg L, Skeppholm M, Terént A. Benefit of anticoagulation unlikely in patients with atrial fibrillation and a CHA2DS2-VASc score of 1. J Am Coll Cardiol 2015; 65:225.
  26. Chao TF, Liu CJ, Wang KL, et al. Using the CHA2DS2-VASc score for refining stroke risk stratification in 'low-risk' Asian patients with atrial fibrillation. J Am Coll Cardiol 2014; 64:1658.
  27. Lip GY, Skjøth F, Rasmussen LH, Larsen TB. Oral anticoagulation, aspirin, or no therapy in patients with nonvalvular AF with 0 or 1 stroke risk factor based on the CHA2DS2-VASc score. J Am Coll Cardiol 2015; 65:1385.
  28. Bekwelem W, Connolly SJ, Halperin JL, et al. Extracranial Systemic Embolic Events in Patients With Nonvalvular Atrial Fibrillation: Incidence, Risk Factors, and Outcomes. Circulation 2015; 132:796.
  29. Johnsen SP, Svendsen ML, Hansen ML, et al. Preadmission oral anticoagulant treatment and clinical outcome among patients hospitalized with acute stroke and atrial fibrillation: a nationwide study. Stroke 2014; 45:168.
  30. Nielsen PB, Skjøth F, Overvad TF, et al. Female Sex Is a Risk Modifier Rather Than a Risk Factor for Stroke in Atrial Fibrillation: Should We Use a CHA2DS2-VA Score Rather Than CHA2DS2-VASc? Circulation 2018; 137:832.
  31. Singer DE, Chang Y, Fang MC, et al. The net clinical benefit of warfarin anticoagulation in atrial fibrillation. Ann Intern Med 2009; 151:297.
  32. Olesen JB, Lip GY, Lindhardsen J, et al. Risks of thromboembolism and bleeding with thromboprophylaxis in patients with atrial fibrillation: A net clinical benefit analysis using a 'real world' nationwide cohort study. Thromb Haemost 2011; 106:739.
  33. Banerjee A, Lane DA, Torp-Pedersen C, Lip GY. Net clinical benefit of new oral anticoagulants (dabigatran, rivaroxaban, apixaban) versus no treatment in a 'real world' atrial fibrillation population: a modelling analysis based on a nationwide cohort study. Thromb Haemost 2012; 107:584.
  34. Go AS, Hylek EM, Chang Y, et al. Anticoagulation therapy for stroke prevention in atrial fibrillation: how well do randomized trials translate into clinical practice? JAMA 2003; 290:2685.
  35. Hart RG, Pearce LA. Current status of stroke risk stratification in patients with atrial fibrillation. Stroke 2009; 40:2607.
  36. Agarwal S, Hachamovitch R, Menon V. Current trial-associated outcomes with warfarin in prevention of stroke in patients with nonvalvular atrial fibrillation: a meta-analysis. Arch Intern Med 2012; 172:623.
  37. Gallagher AM, van Staa TP, Murray-Thomas T, et al. Population-based cohort study of warfarin-treated patients with atrial fibrillation: incidence of cardiovascular and bleeding outcomes. BMJ Open 2014; 4:e003839.
  38. Lip GYH, Banerjee A, Boriani G, et al. Antithrombotic Therapy for Atrial Fibrillation: CHEST Guideline and Expert Panel Report. Chest 2018; 154:1121.
  39. Providência R, Trigo J, Paiva L, Barra S. The role of echocardiography in thromboembolic risk assessment of patients with nonvalvular atrial fibrillation. J Am Soc Echocardiogr 2013; 26:801.
  40. Kezerle L, Tsadok MA, Akriv A, et al. Pre-Diabetes Increases Stroke Risk in Patients With Nonvalvular Atrial Fibrillation. J Am Coll Cardiol 2021; 77:875.
  41. Proietti M, Romiti GF, Vitolo M, et al. Comparison of HAS-BLED and ORBIT bleeding risk scores in atrial fibrillation patients treated with non-vitamin K antagonist oral anticoagulants: a report from the ESC-EHRA EORP-AF General Long-Term Registry. Eur Heart J Qual Care Clin Outcomes 2022; 8:778.
  42. Wattanaruengchai P, Nathisuwan S, Karaketklang K, et al. Comparison of the HAS-BLED versus ORBIT scores in predicting major bleeding among Asians receiving direct-acting oral anticoagulants. Br J Clin Pharmacol 2022; 88:2203.
  43. Poli D, Antonucci E, Grifoni E, et al. Bleeding risk during oral anticoagulation in atrial fibrillation patients older than 80 years. J Am Coll Cardiol 2009; 54:999.
  44. Fuster V, Ryden LE, Cannom DS, et al. ACC/AHA/ESC 2006 Guidelines 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 European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation). J Am Coll Cardiol. 2006; 48:e149.
  45. Hughes M, Lip GY, Guideline Development Group for the NICE national clinical guideline for management of atrial fibrillation in primary and secondary care. Risk factors for anticoagulation-related bleeding complications in patients with atrial fibrillation: a systematic review. QJM 2007; 100:599.
  46. Fang MC, Go AS, Chang Y, et al. Death and disability from warfarin-associated intracranial and extracranial hemorrhages. Am J Med 2007; 120:700.
  47. Otto CM, Nishimura RA, Bonow RO, et al. 2020 ACC/AHA Guideline for the Management of Patients With Valvular Heart Disease: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation 2021; 143:e72.
  48. Van Gelder IC, Healey JS, Crijns HJGM, et al. Duration of device-detected subclinical atrial fibrillation and occurrence of stroke in ASSERT. Eur Heart J 2017; 38:1339.
  49. Diederichsen SZ, Haugan KJ, Brandes A, et al. Natural History of Subclinical Atrial Fibrillation Detected by Implanted Loop Recorders. J Am Coll Cardiol 2019; 74:2771.
  50. McIntyre WF, Benz AP, Becher N, et al. Direct Oral Anticoagulants for Stroke Prevention in Patients with Device-Detected Atrial Fibrillation: A Study-Level Meta-Analysis of the NOAH-AFNET 6 and ARTESiA Trials. Circulation 2023.
  51. Kirchhof P, Toennis T, Goette A, et al. Anticoagulation with Edoxaban in Patients with Atrial High-Rate Episodes. N Engl J Med 2023; 389:1167.
  52. Healey JS, Lopes RD, Granger CB, et al. Apixaban for Stroke Prevention in Subclinical Atrial Fibrillation. N Engl J Med 2024; 390:107.
  53. Chao TF, Liu CJ, Lin YJ, et al. Oral Anticoagulation in Very Elderly Patients With Atrial Fibrillation: A Nationwide Cohort Study. Circulation 2018; 138:37.
  54. Vázquez E, Sánchez-Perales C, Borrego F, et al. Influence of atrial fibrillation on the morbido-mortality of patients on hemodialysis. Am Heart J 2000; 140:886.
  55. Genovesi S, Pogliani D, Faini A, et al. Prevalence of atrial fibrillation and associated factors in a population of long-term hemodialysis patients. Am J Kidney Dis 2005; 46:897.
  56. Vazquez E, Sanchez-Perales C, Garcia-Garcia F, et al. Atrial fibrillation in incident dialysis patients. Kidney Int 2009; 76:324.
  57. Wetmore JB, Mahnken JD, Rigler SK, et al. The prevalence of and factors associated with chronic atrial fibrillation in Medicare/Medicaid-eligible dialysis patients. Kidney Int 2012; 81:469.
  58. Go AS, Hylek EM, Phillips KA, et al. Prevalence of diagnosed atrial fibrillation in adults: national implications for rhythm management and stroke prevention: the AnTicoagulation and Risk Factors in Atrial Fibrillation (ATRIA) Study. JAMA 2001; 285:2370.
  59. Pokorney SD, Black-Maier E, Hellkamp AS, et al. Oral Anticoagulation and Cardiovascular Outcomes in Patients With Atrial Fibrillation and End-Stage Renal Disease. J Am Coll Cardiol 2020; 75:1299.
  60. US Renal Data System: USRDS 2005 Annual Data Report: Atlas of End-Stage Renal Disease in the United States. Bethesda, National Institutes of Health, National Institute of Diabetes, and Digestive and Kidney Diseases, 2005.
  61. Winkelmayer WC, Patrick AR, Liu J, et al. The increasing prevalence of atrial fibrillation among hemodialysis patients. J Am Soc Nephrol 2011; 22:349.
  62. Yang F, Chou D, Schweitzer P, Hanon S. Warfarin in haemodialysis patients with atrial fibrillation: what benefit? Europace 2010; 12:1666.
  63. Marinigh R, Lane DA, Lip GY. Severe renal impairment and stroke prevention in atrial fibrillation: implications for thromboprophylaxis and bleeding risk. J Am Coll Cardiol 2011; 57:1339.
  64. Atar I, Konaş D, Açikel S, et al. Frequency of atrial fibrillation and factors related to its development in dialysis patients. Int J Cardiol 2006; 106:47.
  65. Abbott KC, Trespalacios FC, Taylor AJ, Agodoa LY. Atrial fibrillation in chronic dialysis patients in the United States: risk factors for hospitalization and mortality. BMC Nephrol 2003; 4:1.
  66. K/DOQI Workgroup. K/DOQI clinical practice guidelines for cardiovascular disease in dialysis patients. Am J Kidney Dis 2005; 45:S1.
  67. Bozbas H, Atar I, Yildirir A, et al. Prevalence and predictors of arrhythmia in end stage renal disease patients on hemodialysis. Ren Fail 2007; 29:331.
  68. Go AS, Fang MC, Udaltsova N, et al. Impact of proteinuria and glomerular filtration rate on risk of thromboembolism in atrial fibrillation: the anticoagulation and risk factors in atrial fibrillation (ATRIA) study. Circulation 2009; 119:1363.
  69. Olesen JB, Lip GY, Kamper AL, et al. Stroke and bleeding in atrial fibrillation with chronic kidney disease. N Engl J Med 2012; 367:625.
  70. Limdi NA, Beasley TM, Baird MF, et al. Kidney function influences warfarin responsiveness and hemorrhagic complications. J Am Soc Nephrol 2009; 20:912.
  71. Nakayama M, Metoki H, Terawaki H, et al. Kidney dysfunction as a risk factor for first symptomatic stroke events in a general Japanese population--the Ohasama study. Nephrol Dial Transplant 2007; 22:1910.
  72. Roldán V, Marín F, Manzano-Fernandez S, et al. Does chronic kidney disease improve the predictive value of the CHADS2 and CHA2DS2-VASc stroke stratification risk scores for atrial fibrillation? Thromb Haemost 2013; 109:956.
  73. Kornej J, Hindricks G, Kosiuk J, et al. Renal dysfunction, stroke risk scores (CHADS2, CHA2DS2-VASc, and R2CHADS2), and the risk of thromboembolic events after catheter ablation of atrial fibrillation: the Leipzig Heart Center AF Ablation Registry. Circ Arrhythm Electrophysiol 2013; 6:868.
  74. Ha JT, Neuen BL, Cheng LP, et al. Benefits and Harms of Oral Anticoagulant Therapy in Chronic Kidney Disease: A Systematic Review and Meta-analysis. Ann Intern Med 2019; 171:181.
  75. Chan KE, Lazarus JM, Thadhani R, Hakim RM. Warfarin use associates with increased risk for stroke in hemodialysis patients with atrial fibrillation. J Am Soc Nephrol 2009; 20:2223.
  76. Wizemann V, Tong L, Satayathum S, et al. Atrial fibrillation in hemodialysis patients: clinical features and associations with anticoagulant therapy. Kidney Int 2010; 77:1098.
  77. Winkelmayer WC, Liu J, Setoguchi S, Choudhry NK. Effectiveness and safety of warfarin initiation in older hemodialysis patients with incident atrial fibrillation. Clin J Am Soc Nephrol 2011; 6:2662.
  78. Shah M, Avgil Tsadok M, Jackevicius CA, et al. Warfarin use and the risk for stroke and bleeding in patients with atrial fibrillation undergoing dialysis. Circulation 2014; 129:1196.
  79. Carrero JJ, Evans M, Szummer K, et al. Warfarin, kidney dysfunction, and outcomes following acute myocardial infarction in patients with atrial fibrillation. JAMA 2014; 311:919.
  80. Bonde AN, Lip GY, Kamper AL, et al. Net clinical benefit of antithrombotic therapy in patients with atrial fibrillation and chronic kidney disease: a nationwide observational cohort study. J Am Coll Cardiol 2014; 64:2471.
  81. Randhawa MS, Vishwanath R, Rai MP, et al. Association Between Use of Warfarin for Atrial Fibrillation and Outcomes Among Patients With End-Stage Renal Disease: A Systematic Review and Meta-analysis. JAMA Netw Open 2020; 3:e202175.
  82. ACTIVE Writing Group of the ACTIVE Investigators, Connolly S, Pogue J, et al. Clopidogrel plus aspirin versus oral anticoagulation for atrial fibrillation in the Atrial fibrillation Clopidogrel Trial with Irbesartan for prevention of Vascular Events (ACTIVE W): a randomised controlled trial. Lancet 2006; 367:1903.
  83. ACTIVE Investigators, Connolly SJ, Pogue J, et al. Effect of clopidogrel added to aspirin in patients with atrial fibrillation. N Engl J Med 2009; 360:2066.
  84. Tereshchenko LG, Henrikson CA, Cigarroa J, Steinberg JS. Comparative Effectiveness of Interventions for Stroke Prevention in Atrial Fibrillation: A Network Meta-Analysis. J Am Heart Assoc 2016; 5.
  85. Hylek EM, Singer DE. Risk factors for intracranial hemorrhage in outpatients taking warfarin. Ann Intern Med 1994; 120:897.
  86. Själander S, Själander A, Svensson PJ, Friberg L. Atrial fibrillation patients do not benefit from acetylsalicylic acid. Europace 2014; 16:631.
  87. Connolly SJ, Eikelboom J, Joyner C, et al. Apixaban in patients with atrial fibrillation. N Engl J Med 2011; 364:806.
  88. Adjusted-dose warfarin versus low-intensity, fixed-dose warfarin plus aspirin for high-risk patients with atrial fibrillation: Stroke Prevention in Atrial Fibrillation III randomised clinical trial. Lancet 1996; 348:633.
  89. Gulløv AL, Koefoed BG, Petersen P, et al. Fixed minidose warfarin and aspirin alone and in combination vs adjusted-dose warfarin for stroke prevention in atrial fibrillation: Second Copenhagen Atrial Fibrillation, Aspirin, and Anticoagulation Study. Arch Intern Med 1998; 158:1513.
  90. Flaker GC, Gruber M, Connolly SJ, et al. Risks and benefits of combining aspirin with anticoagulant therapy in patients with atrial fibrillation: an exploratory analysis of stroke prevention using an oral thrombin inhibitor in atrial fibrillation (SPORTIF) trials. Am Heart J 2006; 152:967.
  91. 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. Circulation 2014; 130:e199.
  92. January CT, Wann LS, Calkins H, et al. 2019 AHA/ACC/HRS Focused Update of the 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 Clinical Practice Guidelines and the Heart Rhythm Society in Collaboration With the Society of Thoracic Surgeons. Circulation 2019; 140:e125.
  93. Hindricks G, Potpara T, Dagres N, et al. 2020 ESC Guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS): The Task Force for the diagnosis and management of atrial fibrillation of the European Society of Cardiology (ESC) Developed with the special contribution of the European Heart Rhythm Association (EHRA) of the ESC. Eur Heart J 2021; 42:373.
Topic 128998 Version 12.0

References

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