Atrial fibrillation (AF) is the most prevalent cardiac rhythm disorder in the elderly population and is the leading cause of stroke and systemic embolic events. Although AF is classified clinically according to its duration as paroxysmal, persistent, or permanent,[1] the risk for thromboembolism appears to be consistent among these categories.
AF usually originates in the left atrium at the pulmonary veins and can be easily detected and diagnosed on the basis of an irregular pattern with varying RR intervals on ECG. Because patients with AF may be completely asymptomatic, opportunistic screening for silent AF can be easily performed at low cost and little burden for the patient, and is therefore recommended in patients aged > 65 years by guidelines from the European Society of Cardiology (ESC)[2] and the American Heart Association Stroke Council.[3] There has been increasing interest in the development of smartphone-connected wearable devices that collect the carrier's ECG (usually using a single lead) and issue a warning notice when a suspected pathologic finding is detected. However, none of these devices is currently approved by the US Food and Drug Administration, and patients can be unsettled by false-positive results.
AF is usually not life-threatening, but it can elicit serious complications. Several studies have shown a robust association between AF and thromboembolic events.[4]AF results in a state of hypercoagulation due to stasis and turbulence in the atrial auricles and may trigger the development of clots causing thromboembolic events. However, the link between the timing of stroke and the presence of AF is complex and not well understood. In a study of patients with pacemakers and defibrillators, no temporal relationship between the episodes of AF was identified.[3] Likewise, maintaining sinus rhythm by using electric cardioversion and/or antiarrhythmic drugs does not reduce the risk for stroke. On the contrary, the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) trial suggested a mortality benefit in rate-controlled patients compared with rhythm control.[5]
Furthermore, AF is associated with an increased risk for heart failure, ventricular arrhythmias, and death, and it worsens the prognosis of concomitant cardiovascular diseases. However, it remains uncertain whether AF is causally linked to these conditions.
Calculating Risk
The benefit of anticoagulation for stroke prophylaxis in patients with AF is well established.[6] Several studies also proved that the efficacy of anticoagulation is superior to that of antiplatelet agents alone.[7,8] However, clinicians often face a much more challenging dilemma in identifying the optimum anticoagulation method and determining the patient's risk benefit between the risk for stroke or bleeding. In this regard, the CHA2DS2VASc score—a seven-variable score consisting of age, sex, history of heart failure, hypertension, stroke, vascular disease, and diabetes—has replaced and expanded the previously used CHADS2 score.[9]
The risk for stroke or systemic embolic events grows with increasing scores, and therefore oral anticoagulation should be considered in all patients with a score ≥ 2; patients with a score of 0 are at low risk. The European guidelines[2] also recommend oral anticoagulation in males with a score of 1, whereas the ACC/AHA/HRS guidelines[1] consider a point score of 1 as intermediate risk and antithrombotic or anticoagulant therapy may be withheld, acknowledging uncertainty in the level of evidence. Supporting the US guidelines, a recent systematic review[10] concluded that stroke rates differ substantially among tested cohorts, and indicated that annual stroke rates were < 2% in most patients with CHA2DS2VASc scores of 0-2—the presumed threshold to expect a clinical benefit from anticoagulation therapy.
The trade-off between the risks and the benefits of anticoagulation is often summarized as the net clinical outcome.[11] However, weighting these risks may be difficult, because some elderly patients may perceive suffering from stroke as a larger threat than death from bleeding.
Risk assessment of bleeding is challenging because many bleeding scores share the same variables that are used to estimate the risk for stroke or systemic embolic events. In addition, the presently available bleeding scores exhibit low discrimination, with an area under the curve < 0.70. The HAS-BLED score[4](hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile international normalized ratio, elderly, drug/alcohol use concomitantly) is one of the most established scores, with scores of ≥ 3 indicating a high risk for bleeding.
Alternative scores are the HEMORR2HAGES[12] and ATRIA[13] scores. Of note, the mentioned bleeding scores should not be primarily used as a decision-making tool regarding in which patients to avoid anticoagulation, but to assist in the identification of modifiable risk factors to reduce the risk for major bleeding.
There is growing evidence that biomarkers may become helpful tools in the risk stratification of bleeding events. A multimarker approach using cardiac troponin I, N-terminal pro-B–type natriuretic peptide, and D-dimer levels improved risk stratification when added to the CHA2DS2VASc score.[14] In addition, the ABC bleeding score, a combined clinical and biomarker score that was derived and validated in two modern AF trials, had a higher c-statistic than the HAS-BLED score.[15]
Four non-vitamin K antagonist oral anticoagulants (NOACs) were shown to be noninferior to warfarin in reducing stroke and systemic embolic events and are now available as an alternative to warfarin in patients with AF.[16,17,18] A meta-analysis of the NOAC versus warfarin trials[19] found significant reductions in stroke or systemic embolic events, intracranial hemorrhage, and mortality, but increased risk for gastrointestinal bleeding compared with warfarin. Another meta-analysis examined the risks and benefits of NOACs versus warfarin in patients concomitantly taking aspirin found that NOACs also significantly reduced major bleeding compared with warfarin in these patients.[20]
Other benefits of NOACs, including the rapid onset of therapeutic effect, the lack of food interactions and substantially less frequent drug/drug interactions, and the lack of a monitoring requirement with repeated blood sampling, are appealing to patients despite the higher cost compared with warfarin. NOACs should be used with caution in patients with severe obesity or severely impaired renal function because dosing may be unclear or, in the latter case, pharmacokinetics are affected.[21] In addition, NOACs are contraindicated in patients with mechanical valves or mitral stenosis, those who are pregnant or lactating, and children.[22,23]
Patients on oral anticoagulation may have to stop oral anticoagulation before surgical interventions. The American College of Cardiology provides an electronic BridgeAnticoag app that can be used online or with a smartphone to support clinical decisions regarding interrupting, bridging, and restarting patients on oral anticoagulation.
Gaps in Knowledge
Besides the unanswered questions about low- to intermediate-risk patients with a CHA2DS2-VASc score of 0 or 1 as discussed above, data on the clinical significance of short-term episodes of AF are scarce. Although brief episodes were considered to be associated with an increased risk for thromboembolic events, a recent study showed that episodes of less than 20 seconds did not increase the risk for thromboembolic events, and it may therefore be safe to omit oral anticoagulation in younger patients with short-term AF and a low risk for cardiovascular disease.[24]
Furthermore, the optimum management of patients with AF and concomitant antiplatelet therapy (especially dual-antiplatelet therapy) is not well established, and recommendations regarding the management of patients diverge. Contrary to the ACC/AHA/HRS guidelines, the ESC discourages concomitant antiplatelet therapy in patients with stable coronary artery disease (without recent ACS or revascularization) who are on an anticoagulant.
Even more challenging, the optimum duration and intensity of antithrombotic therapy in concomitant AF after coronary revascularization or acute coronary syndrome remain unclear.
Summary
AF is the most common cardiac arrhythmia and all patients with diagnosed AF should be carefully evaluated for an indication for anticoagulation. The CHA2DS2VASc score is the most established risk score and is recommended by both American and European guidelines.
Oral anticoagulation should be begun in all patients with a CHA2DS2VASc score of 2 or greater. The majority of these patients should preferentially receive a NOAC, owing to the superior efficacy and safety profile of these agents compared with vitamin K antagonists.
Patients with a CHA2DS2VASc score of 1 should be evaluated individually, but female sex alone is not an indication for anticoagulation. Risk stratification for bleeding is challenging and risk scores should be applied to identify modifiable risk factors to reduce the risk for bleeding events, but not as decision tools regarding in which patients to avoid anticoagulation.
Atrial fibrillation (AF) is the most prevalent cardiac rhythm disorder in the elderly population and is the leading cause of stroke and systemic embolic events. Although AF is classified clinically according to its duration as paroxysmal, persistent, or permanent,[1] the risk for thromboembolism appears to be consistent among these categories.
AF usually originates in the left atrium at the pulmonary veins and can be easily detected and diagnosed on the basis of an irregular pattern with varying RR intervals on ECG. Because patients with AF may be completely asymptomatic, opportunistic screening for silent AF can be easily performed at low cost and little burden for the patient, and is therefore recommended in patients aged > 65 years by guidelines from the European Society of Cardiology (ESC)[2] and the American Heart Association Stroke Council.[3] There has been increasing interest in the development of smartphone-connected wearable devices that collect the carrier's ECG (usually using a single lead) and issue a warning notice when a suspected pathologic finding is detected. However, none of these devices is currently approved by the US Food and Drug Administration, and patients can be unsettled by false-positive results.
AF is usually not life-threatening, but it can elicit serious complications. Several studies have shown a robust association between AF and thromboembolic events.[4]AF results in a state of hypercoagulation due to stasis and turbulence in the atrial auricles and may trigger the development of clots causing thromboembolic events. However, the link between the timing of stroke and the presence of AF is complex and not well understood. In a study of patients with pacemakers and defibrillators, no temporal relationship between the episodes of AF was identified.[3] Likewise, maintaining sinus rhythm by using electric cardioversion and/or antiarrhythmic drugs does not reduce the risk for stroke. On the contrary, the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) trial suggested a mortality benefit in rate-controlled patients compared with rhythm control.[5]
Furthermore, AF is associated with an increased risk for heart failure, ventricular arrhythmias, and death, and it worsens the prognosis of concomitant cardiovascular diseases. However, it remains uncertain whether AF is causally linked to these conditions.
Calculating Risk
The benefit of anticoagulation for stroke prophylaxis in patients with AF is well established.[6] Several studies also proved that the efficacy of anticoagulation is superior to that of antiplatelet agents alone.[7,8] However, clinicians often face a much more challenging dilemma in identifying the optimum anticoagulation method and determining the patient's risk benefit between the risk for stroke or bleeding. In this regard, the CHA2DS2VASc score—a seven-variable score consisting of age, sex, history of heart failure, hypertension, stroke, vascular disease, and diabetes—has replaced and expanded the previously used CHADS2 score.[9]
The risk for stroke or systemic embolic events grows with increasing scores, and therefore oral anticoagulation should be considered in all patients with a score ≥ 2; patients with a score of 0 are at low risk. The European guidelines[2] also recommend oral anticoagulation in males with a score of 1, whereas the ACC/AHA/HRS guidelines[1] consider a point score of 1 as intermediate risk and antithrombotic or anticoagulant therapy may be withheld, acknowledging uncertainty in the level of evidence. Supporting the US guidelines, a recent systematic review[10] concluded that stroke rates differ substantially among tested cohorts, and indicated that annual stroke rates were < 2% in most patients with CHA2DS2VASc scores of 0-2—the presumed threshold to expect a clinical benefit from anticoagulation therapy.
The trade-off between the risks and the benefits of anticoagulation is often summarized as the net clinical outcome.[11] However, weighting these risks may be difficult, because some elderly patients may perceive suffering from stroke as a larger threat than death from bleeding.
Risk assessment of bleeding is challenging because many bleeding scores share the same variables that are used to estimate the risk for stroke or systemic embolic events. In addition, the presently available bleeding scores exhibit low discrimination, with an area under the curve < 0.70. The HAS-BLED score[4](hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile international normalized ratio, elderly, drug/alcohol use concomitantly) is one of the most established scores, with scores of ≥ 3 indicating a high risk for bleeding.
Alternative scores are the HEMORR2HAGES[12] and ATRIA[13] scores. Of note, the mentioned bleeding scores should not be primarily used as a decision-making tool regarding in which patients to avoid anticoagulation, but to assist in the identification of modifiable risk factors to reduce the risk for major bleeding.
There is growing evidence that biomarkers may become helpful tools in the risk stratification of bleeding events. A multimarker approach using cardiac troponin I, N-terminal pro-B–type natriuretic peptide, and D-dimer levels improved risk stratification when added to the CHA2DS2VASc score.[14] In addition, the ABC bleeding score, a combined clinical and biomarker score that was derived and validated in two modern AF trials, had a higher c-statistic than the HAS-BLED score.[15]
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